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Sample records for jasmonate signaling pathway

Jasmonic acid signaling modulates ozone-induced hypersensitive cell death.

PubMed

Rao, M V; Lee, H; Creelman, R A; Mullet, J E; Davis, K R

2000-09-01

Recent studies suggest that cross-talk between salicylic acid (SA)-, jasmonic acid (JA)-, and ethylene-dependent signaling pathways regulates plant responses to both abiotic and biotic stress factors. Earlier studies demonstrated that ozone (O(3)) exposure activates a hypersensitive response (HR)-like cell death pathway in the Arabidopsis ecotype Cvi-0. We now have confirmed the role of SA and JA signaling in influencing O(3)-induced cell death. Expression of salicylate hydroxylase (NahG) in Cvi-0 reduced O(3)-induced cell death. Methyl jasmonate (Me-JA) pretreatment of Cvi-0 decreased O(3)-induced H(2)O(2) content and SA concentrations and completely abolished O(3)-induced cell death. Cvi-0 synthesized as much JA as did Col-0 in response to O(3) exposure but exhibited much less sensitivity to exogenous Me-JA. Analyses of the responses to O(3) of the JA-signaling mutants jar1 and fad3/7/8 also demonstrated an antagonistic relationship between JA- and SA-signaling pathways in controlling the magnitude of O(3)-induced HR-like cell death.
Jasmonic Acid Signaling Modulates Ozone-Induced Hypersensitive Cell Death

PubMed Central

Rao, Mulpuri V.; Lee, Hyung-il; Creelman, Robert A.; Mullet, John E.; Davis, Keith R.

2000-01-01

Recent studies suggest that cross-talk between salicylic acid (SA)–, jasmonic acid (JA)–, and ethylene-dependent signaling pathways regulates plant responses to both abiotic and biotic stress factors. Earlier studies demonstrated that ozone (O3) exposure activates a hypersensitive response (HR)–like cell death pathway in the Arabidopsis ecotype Cvi-0. We now have confirmed the role of SA and JA signaling in influencing O3-induced cell death. Expression of salicylate hydroxylase (NahG) in Cvi-0 reduced O3-induced cell death. Methyl jasmonate (Me-JA) pretreatment of Cvi-0 decreased O3-induced H2O2 content and SA concentrations and completely abolished O3-induced cell death. Cvi-0 synthesized as much JA as did Col-0 in response to O3 exposure but exhibited much less sensitivity to exogenous Me-JA. Analyses of the responses to O3 of the JA-signaling mutants jar1 and fad3/7/8 also demonstrated an antagonistic relationship between JA- and SA-signaling pathways in controlling the magnitude of O3-induced HR-like cell death. PMID:11006337
The Arabidopsis mutant cev1 has constitutively active jasmonate and ethylene signal pathways and enhanced resistance to pathogens.

PubMed

Ellis, C; Turner, J G

2001-05-01

Jasmonates (JAs) inhibit plant growth and induce plant defense responses. To define genes in the Arabidopsis JA signal pathway, we screened for mutants with constitutive expression of a luciferase reporter for the JA-responsive promoter from the vegetative storage protein gene VSP1. One mutant, named constitutive expression of VSP1 (cev1), produced plants that were smaller than wild type, had stunted roots with long root hairs, accumulated anthocyanin, had constitutive expression of the defense-related genes VSP1, VSP2, Thi2.1, PDF1.2, and CHI-B, and had enhanced resistance to powdery mildew diseases. Genetic evidence indicated that the cev1 phenotype required both COI1, an essential component of the JA signal pathway, and ETR1, which encodes the ethylene receptor. We conclude that cev1 stimulates both the JA and the ethylene signal pathways and that CEV1 regulates an early step in an Arabidopsis defense pathway.
The Arabidopsis Mutant cev1 Has Constitutively Active Jasmonate and Ethylene Signal Pathways and Enhanced Resistance to Pathogens

PubMed Central

Ellis, Christine; Turner, John G.

2001-01-01

Jasmonates (JAs) inhibit plant growth and induce plant defense responses. To define genes in the Arabidopsis JA signal pathway, we screened for mutants with constitutive expression of a luciferase reporter for the JA-responsive promoter from the vegetative storage protein gene VSP1. One mutant, named constitutive expression of VSP1 (cev1), produced plants that were smaller than wild type, had stunted roots with long root hairs, accumulated anthocyanin, had constitutive expression of the defense-related genes VSP1, VSP2, Thi2.1, PDF1.2, and CHI-B, and had enhanced resistance to powdery mildew diseases. Genetic evidence indicated that the cev1 phenotype required both COI1, an essential component of the JA signal pathway, and ETR1, which encodes the ethylene receptor. We conclude that cev1 stimulates both the JA and the ethylene signal pathways and that CEV1 regulates an early step in an Arabidopsis defense pathway. PMID:11340179
Crosstalk among Jasmonate, Salicylate and Ethylene Signaling Pathways in Plant Disease and Immune Responses.

PubMed

Yang, You-Xin; Ahammed, Golam J; Wu, Caijun; Fan, Shu-ying; Zhou, Yan-Hong

2015-01-01

Phytohormone crosstalk is crucial for plant defenses against pathogens and insects in which salicylic acid (SA), jasmonic acid (JA), and ethylene (ET) play key roles. These low molecular mass signals critically trigger and modulate plant resistance against biotrophic as well as necrotrophic pathogens through a complex signaling network that even involves participation of other hormones. Crosstalk among SA, JA and ET is mediated by different molecular players, considered as integral part of these crosscommunicating signal transduction pathways. Recent progress has revealed that the positive versus negative interactions among those pathways ultimately enable a plant to fine-tune its defense against specific aggressors. On the other hand, pathogens have evolved strategies to manipulate the signaling network to their favour in order to intensify virulence on host plant. Here we review recent advances and current knowledge on the role of classical primary defense hormones SA, JA and ET as well as their synergistic and antagonistic interaction in plant disease and immune responses. Crosstalk with other hormones such as abscisic acid, auxin, brassinosteroids, cytokinins and melatonin is also discussed mainly in plant disease resistance. In addition to our keen focus on hormonal crosstalk, this review also highlights potential implication of positive and negative regulatory interactions for developing an efficient disease management strategy through manipulation of hormone signaling in plant.
Jasmonates: biosynthesis, perception, signal transduction and action in plant stress response, growth and development. An update to the 2007 review in Annals of Botany

PubMed Central

Wasternack, C.; Hause, B.

2013-01-01

Background Jasmonates are important regulators in plant responses to biotic and abiotic stresses as well as in development. Synthesized from lipid-constituents, the initially formed jasmonic acid is converted to different metabolites including the conjugate with isoleucine. Important new components of jasmonate signalling including its receptor were identified, providing deeper insight into the role of jasmonate signalling pathways in stress responses and development. Scope The present review is an update of the review on jasmonates published in this journal in 2007. New data of the last five years are described with emphasis on metabolites of jasmonates, on jasmonate perception and signalling, on cross-talk to other plant hormones and on jasmonate signalling in response to herbivores and pathogens, in symbiotic interactions, in flower development, in root growth and in light perception. Conclusions The last few years have seen breakthroughs in the identification of JASMONATE ZIM DOMAIN (JAZ) proteins and their interactors such as transcription factors and co-repressors, and the crystallization of the jasmonate receptor as well as of the enzyme conjugating jasmonate to amino acids. Now, the complex nature of networks of jasmonate signalling in stress responses and development including hormone cross-talk can be addressed. PMID:23558912
Jasmonate signalling pathway in strawberry: Genome-wide identification, molecular characterization and expression of JAZs and MYCs during fruit development and ripening.

PubMed

Garrido-Bigotes, Adrián; Figueroa, Nicolás E; Figueroa, Pablo M; Figueroa, Carlos R

2018-01-01

Jasmonates (JAs) are signalling molecules involved in stress responses, development and secondary metabolism biosynthesis, although their roles in fleshy-fruit development and ripening processes are not well known. In strawberry fruit, it has been proposed that JAs could regulate the early development through the activation of the JAs biosynthesis. Moreover, it has been reported that JA treatment increases anthocyanin content in strawberry fruit involving the bioactive jasmonate biosynthesis. Nevertheless, JA signalling pathway, of which main components are the COI1-JAZ co-receptor and the MYC transcription factors (TFs), has not been characterized in strawberry until now. Here we identified and characterized the woodland strawberry (Fragaria vesca) JAZ and MYC genes as well as studied their expression during development and ripening stages in commercial strawberry (Fragaria × ananassa) fruit. We described twelve putative JAZ proteins and two MYC TFs, which showed high conservation with respect to their orthologs in Arabidopsis thaliana and in other fleshy-fruit species such as Malus × domestica, Vitis vinifera and Solanum lycopersicum as revealed by gene synteny and phylogenetic analyses. Noteworthy, their expression levels exhibited a significant decrease from fruit development to ripening stages in F. × ananassa, along with others of the JA signalling-related genes such as FaNINJA and FaJAMs, encoding for negative regulators of JA responses. Moreover, we found that main JA signalling-related genes such as FaMYC2, and FaJAZ1 are promptly induced by JA treatment at early times in F. × ananassa fruit. These results suggest the conservation of the canonical JA signalling pathway in strawberry and a possible role of this pathway in early strawberry fruit development, which also correlates negatively with the beginning of the ripening process.
Jasmonate signalling pathway in strawberry: Genome-wide identification, molecular characterization and expression of JAZs and MYCs during fruit development and ripening

PubMed Central

Figueroa, Nicolás E.; Figueroa, Pablo M.

2018-01-01

Jasmonates (JAs) are signalling molecules involved in stress responses, development and secondary metabolism biosynthesis, although their roles in fleshy-fruit development and ripening processes are not well known. In strawberry fruit, it has been proposed that JAs could regulate the early development through the activation of the JAs biosynthesis. Moreover, it has been reported that JA treatment increases anthocyanin content in strawberry fruit involving the bioactive jasmonate biosynthesis. Nevertheless, JA signalling pathway, of which main components are the COI1-JAZ co-receptor and the MYC transcription factors (TFs), has not been characterized in strawberry until now. Here we identified and characterized the woodland strawberry (Fragaria vesca) JAZ and MYC genes as well as studied their expression during development and ripening stages in commercial strawberry (Fragaria × ananassa) fruit. We described twelve putative JAZ proteins and two MYC TFs, which showed high conservation with respect to their orthologs in Arabidopsis thaliana and in other fleshy-fruit species such as Malus × domestica, Vitis vinifera and Solanum lycopersicum as revealed by gene synteny and phylogenetic analyses. Noteworthy, their expression levels exhibited a significant decrease from fruit development to ripening stages in F. × ananassa, along with others of the JA signalling-related genes such as FaNINJA and FaJAMs, encoding for negative regulators of JA responses. Moreover, we found that main JA signalling-related genes such as FaMYC2, and FaJAZ1 are promptly induced by JA treatment at early times in F. × ananassa fruit. These results suggest the conservation of the canonical JA signalling pathway in strawberry and a possible role of this pathway in early strawberry fruit development, which also correlates negatively with the beginning of the ripening process. PMID:29746533
Resolution of growth-defense conflict: mechanistic insights from jasmonate signaling.

PubMed

Guo, Qiang; Major, Ian T; Howe, Gregg A

2018-03-16

Induced plant resistance depends on the production of specialized metabolites that repel attack by biotic aggressors and is often associated with reduced growth of vegetative tissues. Despite progress in understanding the signal transduction networks that control growth-defense tradeoffs, much remains to be learned about how growth rate is coordinated with changes in metabolism during growth-to-defense transitions. Here, we highlight recent advances in jasmonate research to suggest how a major branch of plant immunity is dynamically regulated to calibrate growth-defense balance with shifts in carbon availability. We review evidence that diminished growth, as an integral facet of induced resistance, may optimize the temporal and spatial expression of defense compounds without compromising other critical roles of central metabolism. New insights into the evolution of jasmonate signaling further suggest that opposing selective pressures associated with too much or too little defense may have shaped the emergence of a modular jasmonate pathway that integrates primary and specialized metabolism through the control of repressor-transcription factor complexes. A better understanding of the mechanistic basis of growth-defense balance has important implications for boosting plant productivity, including insights into how these tradeoffs may be uncoupled for agricultural improvement. Copyright © 2018 Elsevier Ltd. All rights reserved.
Development of marker genes for jasmonic acid signaling in shoots and roots of wheat

PubMed Central

Liu, Hongwei; Carvalhais, Lilia Costa; Kazan, Kemal; Schenk, Peer M.

2016-01-01

ABSTRACT The jasmonic acid (JA) signaling pathway plays key roles in a diverse array of plant development, reproduction, and responses to biotic and abiotic stresses. Most of our understanding of the JA signaling pathway derives from the dicot model plant Arabidopsis thaliana, while corresponding knowledge in wheat is somewhat limited. In this study, the expression of 41 genes implicated in the JA signaling pathway has been assessed on 10 day-old bread wheat seedlings, 24 h, 48 h, and 72 h after methyl-jasmonate (MeJA) treatment using quantitative real-time PCR. The examined genes have been previously reported to be involved in JA biosynthesis and catabolism, JA perception and signaling, and pathogen defense in wheat shoots and roots. This study provides evidence to suggest that the effect of MeJA treatment is more prominent in shoots than roots of wheat seedlings, and substantial regulation of the JA pathway-dependent defense genes occurs at 72 h after MeJA treatment. Results show that the expression of 22 genes was significantly affected by MeJA treatment in wheat shoots. However, only PR1.1 and PR3 were significantly differentially expressed in wheat roots, both at 24 h post-MeJA treatment, with other genes showing large variation in their gene expression in roots. While providing marker genes on JA signaling in wheat, future work may focus on elucidating the regulatory function of JA-modulated transcription factors, some of which have well-studied potential orthologs in Arabidopsis. PMID:27115051
Jasmonate is essential for insect defense in Arabidopsis.

PubMed

McConn, M; Creelman, R A; Bell, E; Mullet, J E; Browse, J

1997-05-13

The signaling pathways that allow plants to mount defenses against chewing insects are known to be complex. To investigate the role of jasmonate in wound signaling in Arabidopsis and to test whether parallel or redundant pathways exist for insect defense, we have studied a mutant (fad3-2 fad7-2 fad8) that is deficient in the jasmonate precursor linolenic acid. Mutant plants contained negligible levels of jasmonate and showed extremely high mortality ( approximately 80%) from attack by larvae of a common saprophagous fungal gnat, Bradysia impatiens (Diptera: Sciaridae), even though neighboring wild-type plants were largely unaffected. Application of exogenous methyl jasmonate substantially protected the mutant plants and reduced mortality to approximately 12%. These experiments precisely define the role of jasmonate as being essential for the induction of biologically effective defense in this plant-insect interaction. The transcripts of three wound-responsive genes were shown not to be induced by wounding of mutant plants but the same transcripts could be induced by application of methyl jasmonate. By contrast, measurements of transcript levels for a gene encoding glutathione S-transferase demonstrated that wound induction of this gene is independent of jasmonate synthesis. These results indicate that the mutant will be a good genetic model for testing the practical effectiveness of candidate defense genes.
Nuclear jasmonate and salicylate signaling and crosstalk in defense against pathogens.

PubMed

Gimenez-Ibanez, Selena; Solano, Roberto

2013-01-01

An extraordinary progress has been made over the last two decades on understanding the components and mechanisms governing plant innate immunity. After detection of a pathogen, effective plant resistance depends on the activation of a complex signaling network integrated by small signaling molecules and hormonal pathways, and the balance of these hormone systems determines resistance to particular pathogens. The discovery of new components of hormonal signaling pathways, including plant nuclear hormone receptors, is providing a picture of complex crosstalk and induced hormonal changes that modulate disease and resistance through several protein families that perceive hormones within the nucleus and lead to massive gene induction responses often achieved by de-repression. This review highlights recent advances in our understanding of positive and negative regulators of these hormones signaling pathways that are crucial regulatory targets of hormonal crosstalk in disease and defense. We focus on the most recent discoveries on the jasmonate and salicylate pathway components that explain their crosstalk with other hormonal pathways in the nucleus. We discuss how these components fine-tune defense responses to build a robust plant immune system against a great number of different microbes and, finally, we summarize recent discoveries on specific nuclear hormonal manipulation by microbes which exemplify the ingenious ways by which pathogens can take control over the plant's hormone signaling network to promote disease.
Nuclear jasmonate and salicylate signaling and crosstalk in defense against pathogens

PubMed Central

Gimenez-Ibanez, Selena; Solano, Roberto

2013-01-01

An extraordinary progress has been made over the last two decades on understanding the components and mechanisms governing plant innate immunity. After detection of a pathogen, effective plant resistance depends on the activation of a complex signaling network integrated by small signaling molecules and hormonal pathways, and the balance of these hormone systems determines resistance to particular pathogens. The discovery of new components of hormonal signaling pathways, including plant nuclear hormone receptors, is providing a picture of complex crosstalk and induced hormonal changes that modulate disease and resistance through several protein families that perceive hormones within the nucleus and lead to massive gene induction responses often achieved by de-repression. This review highlights recent advances in our understanding of positive and negative regulators of these hormones signaling pathways that are crucial regulatory targets of hormonal crosstalk in disease and defense. We focus on the most recent discoveries on the jasmonate and salicylate pathway components that explain their crosstalk with other hormonal pathways in the nucleus. We discuss how these components fine-tune defense responses to build a robust plant immune system against a great number of different microbes and, finally, we summarize recent discoveries on specific nuclear hormonal manipulation by microbes which exemplify the ingenious ways by which pathogens can take control over the plant’s hormone signaling network to promote disease. PMID:23577014
Jasmonate is essential for insect defense in Arabidopsis

PubMed Central

McConn, Michele; Creelman, Robert A.; Bell, Erin; Mullet, John E.; Browse, John

1997-01-01

The signaling pathways that allow plants to mount defenses against chewing insects are known to be complex. To investigate the role of jasmonate in wound signaling in Arabidopsis and to test whether parallel or redundant pathways exist for insect defense, we have studied a mutant (fad3–2 fad7–2 fad8) that is deficient in the jasmonate precursor linolenic acid. Mutant plants contained negligible levels of jasmonate and showed extremely high mortality (≈80%) from attack by larvae of a common saprophagous fungal gnat, Bradysia impatiens (Diptera: Sciaridae), even though neighboring wild-type plants were largely unaffected. Application of exogenous methyl jasmonate substantially protected the mutant plants and reduced mortality to ≈12%. These experiments precisely define the role of jasmonate as being essential for the induction of biologically effective defense in this plant–insect interaction. The transcripts of three wound-responsive genes were shown not to be induced by wounding of mutant plants but the same transcripts could be induced by application of methyl jasmonate. By contrast, measurements of transcript levels for a gene encoding glutathione S-transferase demonstrated that wound induction of this gene is independent of jasmonate synthesis. These results indicate that the mutant will be a good genetic model for testing the practical effectiveness of candidate defense genes. PMID:11038546
Ligand-receptor co-evolution shaped the jasmonate pathway in land plants.

PubMed

Monte, Isabel; Ishida, Sakiko; Zamarreño, Angel M; Hamberg, Mats; Franco-Zorrilla, José M; García-Casado, Gloria; Gouhier-Darimont, Caroline; Reymond, Philippe; Takahashi, Kosaku; García-Mina, José M; Nishihama, Ryuichi; Kohchi, Takayuki; Solano, Roberto

2018-05-01

The phytohormone jasmonoyl-isoleucine (JA-Ile) regulates defense, growth and developmental responses in vascular plants. Bryophytes have conserved sequences for all JA-Ile signaling pathway components but lack JA-Ile. We show that, in spite of 450 million years of independent evolution, the JA-Ile receptor COI1 is functionally conserved between the bryophyte Marchantia polymorpha and the eudicot Arabidopsis thaliana but COI1 responds to different ligands in each species. We identified the ligand of Marchantia MpCOI1 as two isomeric forms of the JA-Ile precursor dinor-OPDA (dinor-cis-OPDA and dinor-iso-OPDA). We demonstrate that AtCOI1 functionally complements Mpcoi1 mutation and confers JA-Ile responsiveness and that a single-residue substitution in MpCOI1 is responsible for the evolutionary switch in ligand specificity. Our results identify the ancestral bioactive jasmonate and clarify its biosynthetic pathway, demonstrate the functional conservation of its signaling pathway, and show that JA-Ile and COI1 emergence in vascular plants required co-evolution of hormone biosynthetic complexity and receptor specificity.
Defense to Sclerotinia sclerotiorum in oilseed rape is associated with the sequential activations of salicylic acid signaling and jasmonic acid signaling.

PubMed

Wang, Zheng; Tan, Xiaoli; Zhang, Zhiyan; Gu, Shoulai; Li, Guanying; Shi, Haifeng

2012-03-01

Signaling pathways mediated by salicylic acid (SA) and jasmonic acid (JA) are widely studied in various host-pathogen interactions. For oilseed rape (Brassica napus)-Sclerotinia sclerotiorum interaction, little information of the two signaling molecules has been described in detail. In this study, we showed that the level of SA and JA in B. napus leaves was increased with a distinct temporal profile, respectively, after S. sclerotiorum infection. The application of SA or methyl jasmonate enhanced the resistance to the pathogen. Furthermore, a set of SA and JA signaling marker genes were identified from B. napus and were used to monitor the signaling responses to S. sclerotiorum infection by examining the temporal expression profiles of these marker genes. The SA signaling was activated within 12h post inoculation (hpi) followed by the JA signaling which was activated around 24 hpi. In addition, SA-JA crosstalk genes were activated during this process. These results suggested that defense against S. sclerotiorum in oilseed rape is associated with a sequential activation of SA signaling and JA signaling, which provide important clues for designing strategies to curb diseases caused by S. sclerotioru. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Extracellular ATP Acts on Jasmonate Signaling to Reinforce Plant Defense.

PubMed

Tripathi, Diwaker; Zhang, Tong; Koo, Abraham J; Stacey, Gary; Tanaka, Kiwamu

2018-01-01

Damaged cells send various signals to stimulate defense responses. Recent identification and genetic studies of the plant purinoceptor, P2K1 (also known as DORN1), have demonstrated that extracellular ATP is a signal involved in plant stress responses, including wounding, perhaps to evoke plant defense. However, it remains largely unknown how extracellular ATP induces plant defense responses. Here, we demonstrate that extracellular ATP induces plant defense mediated through activation of the intracellular signaling of jasmonate (JA), a well-characterized defense hormone. In Arabidopsis ( Arabidopsis thaliana ) leaves, ATP pretreatment induced resistance against the necrotrophic fungus, Botrytis cinerea The induced resistance was enhanced in the P2K1 receptor overexpression line, but reduced in the receptor mutant, dorn1 - 3 Mining the transcriptome data revealed that ATP induces a set of JA-induced genes. In addition, the P2K1-associated coexpression network contains defense-related genes, including those encoding jasmonate ZIM-domain (JAZ) proteins, which play key roles as repressors of JA signaling. We examined whether extracellular ATP impacts the stability of JAZ1 in Arabidopsis. The results showed that the JAZ1 stability decreased in response to ATP addition in a proteasome-dependent manner. This reduction required intracellular signaling via second messengers-cytosolic calcium, reactive oxygen species, and nitric oxide. Interestingly, the ATP-induced JAZ1 degradation was attenuated in the JA receptor mutant, coi1 , but not in the JA biosynthesis mutant, aos , or upon addition of JA biosynthesis inhibitors. Immunoprecipitation analysis demonstrated that ATP increases the interaction between COI1 and JAZ1, suggesting direct cross talk between extracellular ATP and JA in intracellular signaling events. Taken together, these results suggest that extracellular ATP signaling directly impacts the JA signaling pathway to maximize plant defense responses. © 2018
Structural basis of JAZ repression of MYC transcription factors in jasmonate signalling

DOE PAGES

Zhang, Feng; Yao, Jian; Ke, Jiyuan; ...

2015-08-10

The plant hormone jasmonate plays crucial roles in regulating plant responses to herbivorous insects and microbial pathogens and is an important regulator of plant growth and development. Key mediators of jasmonate signalling include MYC transcription factors, which are repressed by jasmonate ZIM-domain (JAZ) transcriptional repressors in the resting state. In the presence of active jasmonate, JAZ proteins function as jasmonate co-receptors by forming a hormone-dependent complex with COI1, the F-box subunit of an SCF-type ubiquitin E3 ligase. The hormone-dependent formation of the COI1–JAZ co-receptor complex leads to ubiquitination and proteasome-dependent degradation of JAZ repressors and release of MYC proteins frommore » transcriptional repression. The mechanism by which JAZ proteins repress MYC transcription factors and how JAZ proteins switch between the repressor function in the absence of hormone and the co-receptor function in the presence of hormone remain enigmatic. In this paper, we show that Arabidopsis MYC3 undergoes pronounced conformational changes when bound to the conserved Jas motif of the JAZ9 repressor. The Jas motif, previously shown to bind to hormone as a partly unwound helix, forms a complete α-helix that displaces the amino (N)-terminal helix of MYC3 and becomes an integral part of the MYC N-terminal fold. In this position, the Jas helix competitively inhibits MYC3 interaction with the MED25 subunit of the transcriptional Mediator complex. Finally, our structural and functional studies elucidate a dynamic molecular switch mechanism that governs the repression and activation of a major plant hormone pathway.« less
Top hits in contemporary JAZ: New information on jasmonate signaling

PubMed Central

Chung, Hoo Sun; Niu, Yajie; Browse, John; Howe, Gregg A.

2012-01-01

The phytohormone jasmonate (JA) regulates a wide range of growth, developmental, and defense-related processes during the plant life cycle. Identification of the JAZ family of proteins that repress JA responses has facilitated rapid progress in understanding how this lipid-derived hormone controls gene expression. Recent analysis of JAZ proteins has provided new insight into the nature of the JA receptor, the chemical specificity of signal perception, and cross-talk between JA and other hormone response pathways. Functional diversification of JAZ proteins by alternative splicing, together with the ability of JAZ proteins to homo- and heterodimerize, provide mechanisms to enhance combinatorial diversity and versatility in gene regulation by JA. PMID:19800644
The Jasmonate Pathway Is a Key Player in Systemically Induced Defense against Root Knot Nematodes in Rice1[C

PubMed Central

Nahar, Kamrun; Kyndt, Tina; De Vleesschauwer, David; Höfte, Monica; Gheysen, Godelieve

2011-01-01

Complex defense signaling pathways, controlled by different hormones, are involved in the reaction of plants to a wide range of biotic and abiotic stress factors. We studied the ability of salicylic acid, jasmonate (JA), and ethylene (ET) to induce systemic defense in rice (Oryza sativa) against the root knot nematode Meloidogyne graminicola. Exogenous ET (ethephon) and JA (methyl jasmonate) supply on the shoots induced a strong systemic defense response in the roots, exemplified by a major up-regulation of pathogenesis-related genes OsPR1a and OsPR1b, while the salicylic acid analog BTH (benzo-1,2,3-thiadiazole-7-carbothioic acid S-methyl ester) was a less potent systemic defense inducer from shoot to root. Experiments with JA biosynthesis mutants and ET-insensitive transgenics showed that ET-induced defense requires an intact JA pathway, while JA-induced defense was still functional when ET signaling was impaired. Pharmacological inhibition of JA and ET biosynthesis confirmed that JA biosynthesis is needed for ET-induced systemic defense, and quantitative real-time reverse transcription-polymerase chain reaction data revealed that ET application onto the shoots strongly activates JA biosynthesis and signaling genes in the roots. All data provided in this study point to the JA pathway to play a pivotal role in rice defense against root knot nematodes. The expression of defense-related genes was monitored in root galls caused by M. graminicola. Different analyzed defense genes were attenuated in root galls caused by the nematode at early time points after infection. However, when the exogenous defense inducers ethephon and methyl jasmonate were supplied to the plant, the nematode was less effective in counteracting root defense pathways, hence making the plant more resistant to nematode infection. PMID:21715672

GmCYP82A3, a Soybean Cytochrome P450 Family Gene Involved in the Jasmonic Acid and Ethylene Signaling Pathway, Enhances Plant Resistance to Biotic and Abiotic Stresses

PubMed Central

Yan, Qiang; Cui, Xiaoxia; Lin, Shuai; Gan, Shuping; Xing, Han; Dou, Daolong

2016-01-01

The cytochrome P450 monooxygenases (P450s) represent a large and important enzyme superfamily in plants. They catalyze numerous monooxygenation/hydroxylation reactions in biochemical pathways, P450s are involved in a variety of metabolic pathways and participate in the homeostasis of phytohormones. The CYP82 family genes specifically reside in dicots and are usually induced by distinct environmental stresses. However, their functions are largely unknown, especially in soybean (Glycine max L.). Here, we report the function of GmCYP82A3, a gene from soybean CYP82 family. Its expression was induced by Phytophthora sojae infection, salinity and drought stresses, and treatment with methyl jasmonate (MeJA) or ethephon (ETH). Its expression levels were consistently high in resistant cultivars. Transgenic Nicotiana benthamiana plants overexpressing GmCYP82A3 exhibited strong resistance to Botrytis cinerea and Phytophthora parasitica, and enhanced tolerance to salinity and drought stresses. Furthermore, transgenic plants were less sensitive to jasmonic acid (JA), and the enhanced resistance was accompanied with increased expression of the JA/ET signaling pathway-related genes. PMID:27588421
Nitrogen treatment enhances sterols and withaferin A through transcriptional activation of jasmonate pathway, WRKY transcription factors, and biosynthesis genes in Withania somnifera (L.) Dunal.

PubMed

Pal, Shaifali; Yadav, Akhilesh Kumar; Singh, Anup Kumar; Rastogi, Shubhra; Gupta, Madan Mohan; Verma, Rajesh Kumar; Nagegowda, Dinesh A; Pal, Anirban; Shasany, Ajit Kumar

2017-01-01

The medicinal plant Withania somnifera is researched extensively to increase the quantity of withanolides and specifically withaferin A, which finds implications in many pharmacological activities. Due to insufficient knowledge on biosynthesis and unacceptability of transgenic approach, it is preferred to follow alternative physiological methods to increase the yield of withanolides. Prior use of elicitors like salicylic acid, methyl jasmonate, fungal extracts, and even mechanical wounding have shown to increase the withanolide biosynthesis with limited success; however, the commercial viability and logistics of application are debatable. In this investigation, we tested the simple nitrogeneous fertilizers pertaining to the enhancement of withaferin A biosynthesis. Application of ammonium sulfate improved the sterol contents required for the withanolide biosynthesis and correlated to higher expression of pathway genes like FPPS, SMT1, SMT2, SMO1, SMO2, and ODM. Increased expression of a gene homologous to allene oxide cyclase, crucial in jasmonic acid biosynthetic pathway, suggested the involvement of jasmonate signaling. High levels of WRKY gene transcripts indicated transcriptional regulation of the pathway genes. Increase in transcript level could be correlated with a corresponding increase in the protein levels for WsSMT1 and WsWRKY1. The withaferin A increase was also demonstrated in the potted plants growing in the glasshouse and in the open field. These results implicated simple physiological management of nitrogen fertilizer signal to improve the yield of secondary metabolite through probable involvement of jasmonate signal and WRKY transcription factor for the first time, in W. somnifera besides improving the foliage.
Jasmonate regulates the inducer of cbf expression-C-repeat binding factor/DRE binding factor1 cascade and freezing tolerance in Arabidopsis.

PubMed

Hu, Yanru; Jiang, Liqun; Wang, Fang; Yu, Diqiu

2013-08-01

The inducer of cbf expression (ICE)-C-repeat binding factor/DRE binding factor1 (CBF/DREB1) transcriptional pathway plays a critical role in modulating cold stress responses in Arabidopsis thaliana. Dissecting crucial upstream regulatory signals or components of the ICE-CBF/DREB1 cascade will enhance our understanding of plant cold-tolerance mechanisms. Here, we show that jasmonate positively regulates plant responses to freezing stress in Arabidopsis. Exogenous application of jasmonate significantly enhanced plant freezing tolerance with or without cold acclimation. By contrast, blocking endogenous jasmonate biosynthesis and signaling rendered plants hypersensitive to freezing stress. Consistent with the positive role of jasmonate in freezing stress, production of endogenous jasmonate was triggered by cold treatment. In addition, cold induction of genes acting in the CBF/DREB1 signaling pathway was upregulated by jasmonate. Further investigation revealed that several jasmonate ZIM-domain (JAZ) proteins, the repressors of jasmonate signaling, physically interact with ICE1 and ICE2 transcription factors. JAZ1 and JAZ4 repress the transcriptional function of ICE1, thereby attenuating the expression of its regulon. Consistent with this, overexpression of JAZ1 or JAZ4 represses freezing stress responses of Arabidopsis. Taken together, our study provides evidence that jasmonate functions as a critical upstream signal of the ICE-CBF/DREB1 pathway to positively regulate Arabidopsis freezing tolerance.
Jasmonate Regulates the INDUCER OF CBF EXPRESSION–C-REPEAT BINDING FACTOR/DRE BINDING FACTOR1 Cascade and Freezing Tolerance in Arabidopsis[W

PubMed Central

Hu, Yanru; Jiang, Liqun; Wang, Fang; Yu, Diqiu

2013-01-01

The INDUCER OF CBF EXPRESSION (ICE)–C-REPEAT BINDING FACTOR/DRE BINDING FACTOR1 (CBF/DREB1) transcriptional pathway plays a critical role in modulating cold stress responses in Arabidopsis thaliana. Dissecting crucial upstream regulatory signals or components of the ICE-CBF/DREB1 cascade will enhance our understanding of plant cold-tolerance mechanisms. Here, we show that jasmonate positively regulates plant responses to freezing stress in Arabidopsis. Exogenous application of jasmonate significantly enhanced plant freezing tolerance with or without cold acclimation. By contrast, blocking endogenous jasmonate biosynthesis and signaling rendered plants hypersensitive to freezing stress. Consistent with the positive role of jasmonate in freezing stress, production of endogenous jasmonate was triggered by cold treatment. In addition, cold induction of genes acting in the CBF/DREB1 signaling pathway was upregulated by jasmonate. Further investigation revealed that several JASMONATE ZIM-DOMAIN (JAZ) proteins, the repressors of jasmonate signaling, physically interact with ICE1 and ICE2 transcription factors. JAZ1 and JAZ4 repress the transcriptional function of ICE1, thereby attenuating the expression of its regulon. Consistent with this, overexpression of JAZ1 or JAZ4 represses freezing stress responses of Arabidopsis. Taken together, our study provides evidence that jasmonate functions as a critical upstream signal of the ICE-CBF/DREB1 pathway to positively regulate Arabidopsis freezing tolerance. PMID:23933884
Jasmonates: Multifunctional Roles in Stress Tolerance

PubMed Central

Ahmad, Parvaiz; Rasool, Saiema; Gul, Alvina; Sheikh, Subzar A.; Akram, Nudrat A.; Ashraf, Muhammad; Kazi, A. M.; Gucel, Salih

2016-01-01

Jasmonates (JAs) [Jasmonic acid (JA) and methyl jasmonates (MeJAs)] are known to take part in various physiological processes. Exogenous application of JAs so far tested on different plants under abiotic stresses particularly salinity, drought, and temperature (low/high) conditions have proved effective in improving plant stress tolerance. However, its extent of effectiveness entirely depends on the type of plant species tested or its concentration. The effects of introgression or silencing of different JA- and Me-JA-related genes have been summarized in this review, which have shown a substantial role in improving crop yield and quality in different plants under stress or non-stress conditions. Regulation of JAs synthesis is impaired in stressed as well as unstressed plant cells/tissues, which is believed to be associated with a variety of metabolic events including signal transduction. Although, mitogen activated protein kinases (MAPKs) are important components of JA signaling and biosynthesis pathways, nitric oxide, ROS, calcium, ABA, ethylene, and salicylic acid are also important mediators of plant growth and development during JA signal transduction and synthesis. The exploration of other signaling molecules can be beneficial to examine the details of underlying molecular mechanisms of JA signal transduction. Much work is to be done in near future to find the proper answers of the questions like action of JA related metabolites, and identification of universal JA receptors etc. Complete signaling pathways involving MAPKs, CDPK, TGA, SIPK, WIPK, and WRKY transcription factors are yet to be investigated to understand the complete mechanism of action of JAs. PMID:27379115
The Mediator Complex Subunit PFT1 Is a Key Regulator of Jasmonate-Dependent Defense in Arabidopsis[C][W

PubMed Central

Kidd, Brendan N.; Edgar, Cameron I.; Kumar, Krish K.; Aitken, Elizabeth A.; Schenk, Peer M.; Manners, John M.; Kazan, Kemal

2009-01-01

Jasmonate signaling plays an important role in both plant defense and development. Here, we have identified a subunit of the Mediator complex as a regulator of the jasmonate signaling pathway in Arabidopsis thaliana. The Mediator complex is a conserved multiprotein complex that acts as a universal adaptor between transcription factors and the RNA polymerase II transcriptional machinery. We report that the PHYTOCHROME AND FLOWERING TIME1 (PFT1) gene, which encodes the MEDIATOR25 subunit of Mediator, is required for jasmonate-dependent defense gene expression and resistance to leaf-infecting necrotrophic fungal pathogens. Conversely, PFT1 appears to confer susceptibility to Fusarium oxysporum, a root-infecting hemibiotrophic fungal pathogen known to hijack jasmonate responses for disease development. Consistent with this, jasmonate gene expression was suppressed in the pft1 mutant during infection with F. oxysporum. In addition, a wheat (Triticum aestivum) homolog of PFT1 complemented the defense and the developmental phenotypes of the pft1 mutant, suggesting that the jasmonate signaling functions of PFT1 may be conserved in higher plants. Overall, our results identify an important control point in the regulation of the jasmonate signaling pathway within the transcriptional machinery. PMID:19671879
Alkamides Activate Jasmonic Acid Biosynthesis and Signaling Pathways and Confer Resistance to Botrytis cinerea in Arabidopsis thaliana

PubMed Central

Méndez-Bravo, Alfonso; Calderón-Vázquez, Carlos; Ibarra-Laclette, Enrique; Raya-González, Javier; Ramírez-Chávez, Enrique; Molina-Torres, Jorge; Guevara-García, Angel A.; López-Bucio, José; Herrera-Estrella, Luis

2011-01-01

Alkamides are fatty acid amides of wide distribution in plants, structurally related to N-acyl-L-homoserine lactones (AHLs) from Gram-negative bacteria and to N- acylethanolamines (NAEs) from plants and mammals. Global analysis of gene expression changes in Arabidopsis thaliana in response to N-isobutyl decanamide, the most highly active alkamide identified to date, revealed an overrepresentation of defense-responsive transcriptional networks. In particular, genes encoding enzymes for jasmonic acid (JA) biosynthesis increased their expression, which occurred in parallel with JA, nitric oxide (NO) and H2O2 accumulation. The activity of the alkamide to confer resistance against the necrotizing fungus Botrytis cinerea was tested by inoculating Arabidopsis detached leaves with conidiospores and evaluating disease symptoms and fungal proliferation. N-isobutyl decanamide application significantly reduced necrosis caused by the pathogen and inhibited fungal proliferation. Arabidopsis mutants jar1 and coi1 altered in JA signaling and a MAP kinase mutant (mpk6), unlike salicylic acid- (SA) related mutant eds16/sid2-1, were unable to defend from fungal attack even when N-isobutyl decanamide was supplied, indicating that alkamides could modulate some necrotrophic-associated defense responses through JA-dependent and MPK6-regulated signaling pathways. Our results suggest a role of alkamides in plant immunity induction. PMID:22076141
Involvement of salicylic acid, ethylene and jasmonic acid signalling pathways in the susceptibility of tomato to Fusarium oxysporum.

PubMed

Di, Xiaotang; Gomila, Jo; Takken, Frank L W

2017-09-01

Phytohormones, such as salicylic acid (SA), ethylene (ET) and jasmonic acid (JA), play key roles in plant defence following pathogen attack. The involvement of these hormones in susceptibility following Fusarium oxysporum (Fo) infection has mostly been studied in Arabidopsis thaliana. However, Fo causes vascular wilt disease in a broad range of crops, including tomato (Solanum lycopersicum). Surprisingly little is known about the involvement of these phytohormones in the susceptibility of tomato towards Fo f. sp. lycopersici (Fol). Here, we investigate their involvement by the analysis of the expression of ET, JA and SA marker genes following Fol infection, and by bioassays of tomato mutants affected in either hormone production or perception. Fol inoculation triggered the expression of SA and ET marker genes, showing the activation of these pathways. NahG tomato, in which SA is degraded, became hypersusceptible to Fol infection and showed stronger disease symptoms than wild-type. In contrast, ACD and Never ripe (Nr) mutants, in which ET biosynthesis and perception, respectively, are impaired, showed decreased disease symptoms and reduced fungal colonization on infection. The susceptibility of the def1 tomato mutant, and a prosystemin over-expressing line, in which JA signalling is compromised or constitutively activated, respectively, was unaltered. Our results show that SA is a negative and ET a positive regulator of Fol susceptibility. The SA and ET signalling pathways appear to act synergistically, as an intact ET pathway is required for the induction of an SA marker gene, and vice versa. © 2017 THE AUTHORS. MOLECULAR PLANT PATHOLOGY PUBLISHED BY BRITISH SOCIETY FOR PLANT PATHOLOGY AND JOHN WILEY & SONS LTD.
Jasmonate signaling is activated in the very early stages of iron deficiency responses in rice roots.

PubMed

Kobayashi, Takanori; Itai, Reiko Nakanishi; Senoura, Takeshi; Oikawa, Takaya; Ishimaru, Yasuhiro; Ueda, Minoru; Nakanishi, Hiromi; Nishizawa, Naoko K

2016-07-01

Under low iron availability, plants induce the expression of various genes involved in iron uptake and translocation at the transcriptional level. This iron deficiency response is affected by various plant hormones, but the roles of jasmonates in this response are not well-known. We investigated the involvement of jasmonates in rice iron deficiency responses. High rates of jasmonate-inducible genes were induced during the very early stages of iron deficiency treatment in rice roots. Many jasmonate-inducible genes were also negatively regulated by the ubiquitin ligases OsHRZ1 and OsHRZ2 and positively regulated by the transcription factor IDEF1. Ten out of 35 genes involved in jasmonate biosynthesis and signaling were rapidly induced at 3 h of iron deficiency treatment, and this induction preceded that of known iron deficiency-inducible genes involved in iron uptake and translocation. Twelve genes involved in jasmonate biosynthesis and signaling were also upregulated in HRZ-knockdown roots. Endogenous concentrations of jasmonic acid and jasmonoyl isoleucine tended to be rapidly increased in roots in response to iron deficiency treatment, whereas these concentrations were higher in HRZ-knockdown roots under iron-sufficient conditions. Analysis of the jasmonate-deficient cpm2 mutant revealed that jasmonates repress the expression of many iron deficiency-inducible genes involved in iron uptake and translocation under iron sufficiency, but this repression is partly canceled under an early stage of iron deficiency. These results indicate that jasmonate signaling is activated during the very early stages of iron deficiency, which is partly regulated by IDEF1 and OsHRZs.
Plants on constant alert: elevated levels of jasmonic acid and jasmonate-induced transcripts in caterpillar resistant maize

USDA-ARS?s Scientific Manuscript database

Plant defense responses against insect herbivores frequently depend on the biosynthesis and action of jasmonic acid (JA) and its conjugates. To better understand JA signaling pathways in maize (Zea mays L.), we have examined two maize genotypes, Mp708 and Tx601. Mp708 is resistant to feeding by le...
Integrating nitric oxide into salicylic acid and jasmonic acid/ ethylene plant defense pathways.

PubMed

Mur, Luis A J; Prats, Elena; Pierre, Sandra; Hall, Michael A; Hebelstrup, Kim H

2013-01-01

Plant defense against pests and pathogens is known to be conferred by either salicylic acid (SA) or jasmonic acid (JA)/ethylene (ET) pathways, depending on infection or herbivore-grazing strategy. It is well attested that SA and JA/ET pathways are mutually antagonistic allowing defense responses to be tailored to particular biotic stresses. Nitric oxide (NO) has emerged as a major signal influencing resistance mediated by both signaling pathways but no attempt has been made to integrate NO into established SA/JA/ET interactions. NO has been shown to act as an inducer or suppressor of signaling along each pathway. NO will initiate SA biosynthesis and nitrosylate key cysteines on TGA-class transcription factors to aid in the initiation of SA-dependent gene expression. Against this, S-nitrosylation of NONEXPRESSOR OF PATHOGENESIS-RELATED PROTEINS1 (NPR1) will promote the NPR1 oligomerization within the cytoplasm to reduce TGA activation. In JA biosynthesis, NO will initiate the expression of JA biosynthetic enzymes, presumably to over-come any antagonistic effects of SA on JA-mediated transcription. NO will also initiate the expression of ET biosynthetic genes but a suppressive role is also observed in the S-nitrosylation and inhibition of S-adenosylmethionine transferases which provides methyl groups for ET production. Based on these data a model for NO action is proposed but we have also highlighted the need to understand when and how inductive and suppressive steps are used.
Integrating nitric oxide into salicylic acid and jasmonic acid/ ethylene plant defense pathways

PubMed Central

Mur, Luis A. J.; Prats, Elena; Pierre, Sandra; Hall, Michael A.; Hebelstrup, Kim H.

2013-01-01

Plant defense against pests and pathogens is known to be conferred by either salicylic acid (SA) or jasmonic acid (JA)/ethylene (ET) pathways, depending on infection or herbivore-grazing strategy. It is well attested that SA and JA/ET pathways are mutually antagonistic allowing defense responses to be tailored to particular biotic stresses. Nitric oxide (NO) has emerged as a major signal influencing resistance mediated by both signaling pathways but no attempt has been made to integrate NO into established SA/JA/ET interactions. NO has been shown to act as an inducer or suppressor of signaling along each pathway. NO will initiate SA biosynthesis and nitrosylate key cysteines on TGA-class transcription factors to aid in the initiation of SA-dependent gene expression. Against this, S-nitrosylation of NONEXPRESSOR OF PATHOGENESIS-RELATED PROTEINS1 (NPR1) will promote the NPR1 oligomerization within the cytoplasm to reduce TGA activation. In JA biosynthesis, NO will initiate the expression of JA biosynthetic enzymes, presumably to over-come any antagonistic effects of SA on JA-mediated transcription. NO will also initiate the expression of ET biosynthetic genes but a suppressive role is also observed in the S-nitrosylation and inhibition of S-adenosylmethionine transferases which provides methyl groups for ET production. Based on these data a model for NO action is proposed but we have also highlighted the need to understand when and how inductive and suppressive steps are used. PMID:23818890
The Transcription Factor ABI4 Is Required for the Ascorbic Acid–Dependent Regulation of Growth and Regulation of Jasmonate-Dependent Defense Signaling Pathways in Arabidopsis[C][W

PubMed Central

Kerchev, Pavel I.; Pellny, Till K.; Vivancos, Pedro Diaz; Kiddle, Guy; Hedden, Peter; Driscoll, Simon; Vanacker, Hélène; Verrier, Paul; Hancock, Robert D.; Foyer, Christine H.

2011-01-01

Cellular redox homeostasis is a hub for signal integration. Interactions between redox metabolism and the ABSCISIC ACID-INSENSITIVE-4 (ABI4) transcription factor were characterized in the Arabidopsis thaliana vitamin c defective1 (vtc1) and vtc2 mutants, which are defective in ascorbic acid synthesis and show a slow growth phenotype together with enhanced abscisic acid (ABA) levels relative to the wild type (Columbia-0). The 75% decrease in the leaf ascorbate pool in the vtc2 mutants was not sufficient to adversely affect GA metabolism. The transcriptome signatures of the abi4, vtc1, and vtc2 mutants showed significant overlap, with a large number of transcription factors or signaling components similarly repressed or induced. Moreover, lincomycin-dependent changes in LIGHT HARVESTING CHLOROPHYLL A/B BINDING PROTEIN 1.1 expression were comparable in these mutants, suggesting overlapping participation in chloroplast to nucleus signaling. The slow growth phenotype of vtc2 was absent in the abi4 vtc2 double mutant, as was the sugar-insensitive phenotype of the abi4 mutant. Octadecanoid derivative-responsive AP2/ERF-domain transcription factor 47 (ORA47) and AP3 (an ABI5 binding factor) transcripts were enhanced in vtc2 but repressed in abi4 vtc2, suggesting that ABI4 and ascorbate modulate growth and defense gene expression through jasmonate signaling. We conclude that low ascorbate triggers ABA- and jasmonate-dependent signaling pathways that together regulate growth through ABI4. Moreover, cellular redox homeostasis exerts a strong influence on sugar-dependent growth regulation. PMID:21926335
Gaseous 3-pentanol primes plant immunity against a bacterial speck pathogen, Pseudomonas syringae pv. tomato via salicylic acid and jasmonic acid-dependent signaling pathways in Arabidopsis.

PubMed

Song, Geun C; Choi, Hye K; Ryu, Choong-Min

2015-01-01

3-Pentanol is an active organic compound produced by plants and is a component of emitted insect sex pheromones. A previous study reported that drench application of 3-pentanol elicited plant immunity against microbial pathogens and an insect pest in crop plants. Here, we evaluated whether 3-pentanol and the derivatives 1-pentanol and 2-pentanol induced plant systemic resistance using the in vitro I-plate system. Exposure of Arabidopsis seedlings to 10 μM and 100 nM 3-pentanol evaporate elicited an immune response to Pseudomonas syringae pv. tomato DC3000. We performed quantitative real-time PCR to investigate the 3-pentanol-mediated Arabidopsis immune responses by determining Pathogenesis-Related (PR) gene expression levels associated with defense signaling through salicylic acid (SA), jasmonic acid (JA), and ethylene signaling pathways. The results show that exposure to 3-pentanol and subsequent pathogen challenge upregulated PDF1.2 and PR1 expression. Selected Arabidopsis mutants confirmed that the 3-pentanol-mediated immune response involved SA and JA signaling pathways and the NPR1 gene. Taken together, this study indicates that gaseous 3-pentanol triggers induced resistance in Arabidopsis by priming SA and JA signaling pathways. To our knowledge, this is the first report that a volatile compound of an insect sex pheromone triggers plant systemic resistance against a bacterial pathogen.
BIOSYNTHESIS AND ACTION OF JASMONATES IN PLANTS.

PubMed

Creelman, Robert A.; Mullet, John E.

1997-06-01

Jasmonic acid and its derivatives can modulate aspects of fruit ripening, production of viable pollen, root growth, tendril coiling, and plant resistance to insects and pathogens. Jasmonate activates genes involved in pathogen and insect resistance, and genes encoding vegetative storage proteins, but represses genes encoding proteins involved in photosynthesis. Jasmonic acid is derived from linolenic acid, and most of the enzymes in the biosynthetic pathway have been extensively characterized. Modulation of lipoxygenase and allene oxide synthase gene expression in transgenic plants raises new questions about the compartmentation of the biosynthetic pathway and its regulation. The activation of jasmonic acid biosynthesis by cell wall elicitors, the peptide systemin, and other compounds will be related to the function of jasmonates in plants. Jasmonate modulates gene expression at the level of translation, RNA processing, and transcription. Promoter elements that mediate responses to jasmonate have been isolated. This review covers recent advances in our understanding of how jasmonate biosynthesis is regulated and relates this information to knowledge of jasmonate modulated gene expression.
RNA-seq based transcriptomic analysis uncovers α-linolenic acid and jasmonic acid biosynthesis pathways respond to cold acclimation in Camellia japonica

PubMed Central

Li, Qingyuan; Lei, Sheng; Du, Kebing; Li, Lizhi; Pang, Xufeng; Wang, Zhanchang; Wei, Ming; Fu, Shao; Hu, Limin; Xu, Lin

2016-01-01

Camellia is a well-known ornamental flower native to Southeast of Asia, including regions such as Japan, Korea and South China. However, most species in the genus Camellia are cold sensitive. To elucidate the cold stress responses in camellia plants, we carried out deep transcriptome sequencing of ‘Jiangxue’, a cold-tolerant cultivar of Camellia japonica, and approximately 1,006 million clean reads were generated using Illumina sequencing technology. The assembly of the clean reads produced 367,620 transcripts, including 207,592 unigenes. Overall, 28,038 differentially expressed genes were identified during cold acclimation. Detailed elucidation of responses of transcription factors, protein kinases and plant hormone signalling-related genes described the interplay of signal that allowed the plant to fine-tune cold stress responses. On the basis of global gene regulation of unsaturated fatty acid biosynthesis- and jasmonic acid biosynthesis-related genes, unsaturated fatty acid biosynthesis and jasmonic acid biosynthesis pathways were deduced to be involved in the low temperature responses in C. japonica. These results were supported by the determination of the fatty acid composition and jasmonic acid content. Our results provide insights into the genetic and molecular basis of the responses to cold acclimation in camellia plants. PMID:27819341
Proteomic analysis of JAZ interacting proteins under methyl jasmonate treatment in finger millet.

PubMed

Sen, Saswati; Kundu, Sangeeta; Dutta, Samir Kr

2016-11-01

Jasmonic acid (JA) signaling pathway in plants is activated against various developmental processes as well as biotic and abiotic stresses. The Jasmonate ZIM-domain (JAZ) protein family, the key regulator of plant JA signaling pathway, also participates in phytohormone crosstalk. This is the first study revealing the in vivo interactions of finger millet (Eleusine coracana (L.) Gaertn.) JAZ protein (EcJAZ) under methyl jasmonate (MJ) treatment. The aim of the study was to explore not only the JA signaling pathway but also the phytohormone signaling crosstalk of finger millet, a highly important future crop. From the MJ-treated finger millet seedlings, the EcJAZ interacting proteins were purified by affinity chromatography with the EcJAZ-matrix. Twenty-one proteins of varying functionalities were successfully identified by MALDI-TOF-TOF Mass spectrometry. Apart from the previously identified JAZ binding proteins, most prominently, EcJAZ was found to interact with transcription factors like NAC, GATA and also with Cold responsive protein (COR), etc. that might have extended the range of functionalities of JAZ proteins. Moreover, to evaluate the interactions of EcJAZ in the JA-co-receptor complex, we generated ten in-silico models containing the EcJAZ degron and the COI1-SKP1 of five monocot cereals viz., rice, wheat, maize, Sorghum and Setaria with JA-Ile or coronatine. Our results indicated that the EcJAZ protein of finger millet could act as the signaling hub for the JA and other phytohormone signaling pathways, in response to a diverse set of stressors and developmental cues to provide survival fitness to the plant. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
Ethylene signaling renders the jasmonate response of Arabidopsis insensitive to future suppression by salicylic Acid.

PubMed

Leon-Reyes, Antonio; Du, Yujuan; Koornneef, Annemart; Proietti, Silvia; Körbes, Ana P; Memelink, Johan; Pieterse, Corné M J; Ritsema, Tita

2010-02-01

Cross-talk between jasmonate (JA), ethylene (ET), and Salicylic acid (SA) signaling is thought to operate as a mechanism to fine-tune induced defenses that are activated in response to multiple attackers. Here, 43 Arabidopsis genotypes impaired in hormone signaling or defense-related processes were screened for their ability to express SA-mediated suppression of JA-responsive gene expression. Mutant cev1, which displays constitutive expression of JA and ET responses, appeared to be insensitive to SA-mediated suppression of the JA-responsive marker genes PDF1.2 and VSP2. Accordingly, strong activation of JA and ET responses by the necrotrophic pathogens Botrytis cinerea and Alternaria brassicicola prior to SA treatment counteracted the ability of SA to suppress the JA response. Pharmacological assays, mutant analysis, and studies with the ET-signaling inhibitor 1-methylcyclopropene revealed that ET signaling renders the JA response insensitive to subsequent suppression by SA. The APETALA2/ETHYLENE RESPONSE FACTOR transcription factor ORA59, which regulates JA/ET-responsive genes such as PDF1.2, emerged as a potential mediator in this process. Collectively, our results point to a model in which simultaneous induction of the JA and ET pathway renders the plant insensitive to future SA-mediated suppression of JA-dependent defenses, which may prioritize the JA/ET pathway over the SA pathway during multi-attacker interactions.
The Arabidopsis mutant cev1 links cell wall signaling to jasmonate and ethylene responses.

PubMed

Ellis, Christine; Karafyllidis, Ioannis; Wasternack, Claus; Turner, John G

2002-07-01

Biotic and abiotic stresses stimulate the synthesis of jasmonates and ethylene, which, in turn, induce the expression of genes involved in stress response and enhance defense responses. The cev1 mutant has constitutive expression of stress response genes and has enhanced resistance to fungal pathogens. Here, we show that cev1 plants have increased production of jasmonate and ethylene and that its phenotype is suppressed by mutations that interrupt jasmonate and ethylene signaling. Genetic mapping, complementation analysis, and sequence analysis revealed that CEV1 is the cellulose synthase CeSA3. CEV1 was expressed predominantly in root tissues, and cev1 roots contained less cellulose than wild-type roots. Significantly, the cev1 mutant phenotype could be reproduced by treating wild-type plants with cellulose biosynthesis inhibitors, and the cellulose synthase mutant rsw1 also had constitutive expression of VSP. We propose that the cell wall can signal stress responses in plants.
The Arabidopsis Mutant cev1 Links Cell Wall Signaling to Jasmonate and Ethylene Responses

PubMed Central

Ellis, Christine; Karafyllidis, Ioannis; Wasternack, Claus; Turner, John G.

2002-01-01

Biotic and abiotic stresses stimulate the synthesis of jasmonates and ethylene, which, in turn, induce the expression of genes involved in stress response and enhance defense responses. The cev1 mutant has constitutive expression of stress response genes and has enhanced resistance to fungal pathogens. Here, we show that cev1 plants have increased production of jasmonate and ethylene and that its phenotype is suppressed by mutations that interrupt jasmonate and ethylene signaling. Genetic mapping, complementation analysis, and sequence analysis revealed that CEV1 is the cellulose synthase CeSA3. CEV1 was expressed predominantly in root tissues, and cev1 roots contained less cellulose than wild-type roots. Significantly, the cev1 mutant phenotype could be reproduced by treating wild-type plants with cellulose biosynthesis inhibitors, and the cellulose synthase mutant rsw1 also had constitutive expression of VSP. We propose that the cell wall can signal stress responses in plants. PMID:12119374

Jasmonate and Phytochrome A Signaling in Arabidopsis Wound and Shade Responses Are Integrated through JAZ1 Stability[C][W

PubMed Central

Robson, Frances; Okamoto, Haruko; Patrick, Elaine; Harris, Sue-Ré; Wasternack, Claus; Brearley, Charles; Turner, John G.

2010-01-01

Jasmonate (JA) activates plant defense, promotes pollen maturation, and suppresses plant growth. An emerging theme in JA biology is its involvement in light responses; here, we examine the interdependence of the JA- and light-signaling pathways in Arabidopsis thaliana. We demonstrate that mutants deficient in JA biosynthesis and signaling are deficient in a subset of high irradiance responses in far-red (FR) light. These mutants display exaggerated shade responses to low, but not high, R/FR ratio light, suggesting a role for JA in phytochrome A (phyA) signaling. Additionally, we demonstrate that the FR light–induced expression of transcription factor genes is dependent on CORONATINE INSENSITIVE1 (COI1), a central component of JA signaling, and is suppressed by JA. phyA mutants had reduced JA-regulated growth inhibition and VSP expression and increased content of cis-(+)-12-oxophytodienoic acid, an intermediate in JA biosynthesis. Significantly, COI1-mediated degradation of JASMONATE ZIM DOMAIN1-β-glucuronidase (JAZ1-GUS) in response to mechanical wounding and JA treatment required phyA, and ectopic expression of JAZ1-GUS resulted in exaggerated shade responses. Together, these results indicate that JA and phyA signaling are integrated through degradation of the JAZ1 protein, and both are required for plant responses to light and stress. PMID:20435902
Simultaneous Determination of Salicylic Acid, Jasmonic Acid, Methyl Salicylate, and Methyl Jasmonate from Ulmus pumila Leaves by GC-MS

PubMed Central

Huang, Zhi-hong; Wang, Zhi-li; Shi, Bao-lin; Wei, Dong; Chen, Jian-xin; Wang, Su-li; Gao, Bao-jia

2015-01-01

Salicylic acid, jasmonic acid, methyl salicylate, and methyl jasmonate are important phytohormones and defensive signaling compounds, so it is of great importance to determine their levels rapidly and accurately. The study uses Ulmus pumila leaves infected by Tetraneura akinire Sasaki at different stages as materials; after extraction with 80% methanol and ethyl acetate and purification with primary secondary amine (PSA) and graphitized carbon blacks (GCB), the contents of signal compounds salicylic acid, jasmonic acid, methyl salicylate, and methyl jasmonate were determined by GC-MS. The results showed that the level of salicylic acid, jasmonic acid, methyl salicylate, and methyl jasmonate increased remarkably in U. pumila once infected by T. akinire Sasaki, but the maximums of these four compounds occurred at different times. Salicylic acid level reached the highest at the early stage, and jasmonic acid level went to the maximum in the middle stage; by contrast, change of content of methyl salicylate and methyl jasmonate was the quite opposite. PMID:26457083
Simultaneous Determination of Salicylic Acid, Jasmonic Acid, Methyl Salicylate, and Methyl Jasmonate from Ulmus pumila Leaves by GC-MS.

PubMed

Huang, Zhi-Hong; Wang, Zhi-Li; Shi, Bao-Lin; Wei, Dong; Chen, Jian-Xin; Wang, Su-Li; Gao, Bao-Jia

2015-01-01

Salicylic acid, jasmonic acid, methyl salicylate, and methyl jasmonate are important phytohormones and defensive signaling compounds, so it is of great importance to determine their levels rapidly and accurately. The study uses Ulmus pumila leaves infected by Tetraneura akinire Sasaki at different stages as materials; after extraction with 80% methanol and ethyl acetate and purification with primary secondary amine (PSA) and graphitized carbon blacks (GCB), the contents of signal compounds salicylic acid, jasmonic acid, methyl salicylate, and methyl jasmonate were determined by GC-MS. The results showed that the level of salicylic acid, jasmonic acid, methyl salicylate, and methyl jasmonate increased remarkably in U. pumila once infected by T. akinire Sasaki, but the maximums of these four compounds occurred at different times. Salicylic acid level reached the highest at the early stage, and jasmonic acid level went to the maximum in the middle stage; by contrast, change of content of methyl salicylate and methyl jasmonate was the quite opposite.
Rewiring of jasmonate and phytochrome B signalling uncouples plant growth-defense tradeoffs

PubMed Central

Campos, Marcelo L.; Yoshida, Yuki; Major, Ian T.; de Oliveira Ferreira, Dalton; Weraduwage, Sarathi M.; Froehlich, John E.; Johnson, Brendan F.; Kramer, David M.; Jander, Georg; Sharkey, Thomas D.; Howe, Gregg A.

2016-01-01

Plants resist infection and herbivory with innate immune responses that are often associated with reduced growth. Despite the importance of growth-defense tradeoffs in shaping plant productivity in natural and agricultural ecosystems, the molecular mechanisms that link growth and immunity are poorly understood. Here, we demonstrate that growth-defense tradeoffs mediated by the hormone jasmonate are uncoupled in an Arabidopsis mutant (jazQ phyB) lacking a quintet of Jasmonate ZIM-domain transcriptional repressors and the photoreceptor phyB. Analysis of epistatic interactions between jazQ and phyB reveal that growth inhibition associated with enhanced anti-insect resistance is likely not caused by diversion of photoassimilates from growth to defense but rather by a conserved transcriptional network that is hardwired to attenuate growth upon activation of jasmonate signalling. The ability to unlock growth-defense tradeoffs through relief of transcription repression provides an approach to assemble functional plant traits in new and potentially useful ways. PMID:27573094
Rewiring of jasmonate and phytochrome B signalling uncouples plant growth-defense tradeoffs

DOE PAGES

Campos, Marcelo L.; Yoshida, Yuki; Major, Ian T.; ...

2016-08-30

Plants resist infection and herbivory with innate immune responses that are often associated with reduced growth. Despite the importance of growth-defense tradeoffs in shaping plant productivity in natural and agricultural ecosystems, the molecular mechanisms that link growth and immunity are poorly understood. Here, we demonstrate that growth-defense tradeoffs mediated by the hormone jasmonate are uncoupled in an Arabidopsis mutant ( jazQ phyB) lacking a quintet of Jasmonate ZIM-domain transcriptional repressors and the photoreceptor phyB. Analysis of epistatic interactions between jazQ and phyB reveal that growth inhibition associated with enhanced anti-insect resistance is likely not caused by diversion of photoassimilates frommore » growth to defense but rather by a conserved transcriptional network that is hardwired to attenuate growth upon activation of jasmonate signalling. Furthermore, the ability to unlock growth-defense tradeoffs through relief of transcription repression provides an approach to assemble functional plant traits in new and potentially useful ways.« less
Rewiring of jasmonate and phytochrome B signalling uncouples plant growth-defense tradeoffs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Campos, Marcelo L.; Yoshida, Yuki; Major, Ian T.

Plants resist infection and herbivory with innate immune responses that are often associated with reduced growth. Despite the importance of growth-defense tradeoffs in shaping plant productivity in natural and agricultural ecosystems, the molecular mechanisms that link growth and immunity are poorly understood. Here, we demonstrate that growth-defense tradeoffs mediated by the hormone jasmonate are uncoupled in an Arabidopsis mutant ( jazQ phyB) lacking a quintet of Jasmonate ZIM-domain transcriptional repressors and the photoreceptor phyB. Analysis of epistatic interactions between jazQ and phyB reveal that growth inhibition associated with enhanced anti-insect resistance is likely not caused by diversion of photoassimilates frommore » growth to defense but rather by a conserved transcriptional network that is hardwired to attenuate growth upon activation of jasmonate signalling. Furthermore, the ability to unlock growth-defense tradeoffs through relief of transcription repression provides an approach to assemble functional plant traits in new and potentially useful ways.« less
The Lateral Organ Boundaries Domain Transcription Factor LBD20 Functions in Fusarium Wilt Susceptibility and Jasmonate Signaling in Arabidopsis1[W

PubMed Central

Thatcher, Louise F.; Powell, Jonathan J.; Aitken, Elizabeth A.B.; Kazan, Kemal; Manners, John M.

2012-01-01

The LATERAL ORGAN BOUNDARIES (LOB) DOMAIN (LBD) gene family encodes plant-specific transcriptional regulators functioning in organ development. In a screen of Arabidopsis (Arabidopsis thaliana) sequence-indexed transferred DNA insertion mutants, we found disruption of the LOB DOMAIN-CONTAINING PROTEIN20 (LBD20) gene led to increased resistance to the root-infecting vascular wilt pathogen Fusarium oxysporum. In wild-type plants, LBD20 transcripts were barely detectable in leaves but abundant in roots, where they were further induced after F. oxysporum inoculation or methyl jasmonate treatment. Induction of LBD20 expression in roots was abolished in coronatine insensitive1 (coi1) and myc2 (allelic to jasmonate insensitive1) mutants, suggesting LBD20 may function in jasmonate (JA) signaling. Consistent with this, expression of the JA-regulated THIONIN2.1 (Thi2.1) and VEGETATIVE STORAGE PROTEIN2 (VSP2) genes were up-regulated in shoots of lbd20 following treatment of roots with F. oxysporum or methyl jasmonate. However, PLANT DEFENSIN1.2 expression was unaltered, indicating a repressor role for LBD20 in a branch of the JA-signaling pathway. Plants overexpressing LBD20 (LBD20-OX) had reduced Thi2.1 and VSP2 expression. There was a significant correlation between increased LBD20 expression in the LBD20-OX lines with both Thi2.1 and VSP2 repression, and reduced survival following F. oxysporum infection. Chlorosis resulting from application of F. oxysporum culture filtrate was also reduced in lbd20 leaves relative to the wild type. Taken together, LBD20 is a F. oxysporum susceptibility gene that appears to regulate components of JA signaling downstream of COI1 and MYC2 that are required for full elicitation of F. oxysporum- and JA-dependent responses. To our knowledge, this is the first demonstration of a role for a LBD gene family member in either biotic stress or JA signaling. PMID:22786889
The platelet-activating factor acetylhydrolase gene derived from Trichoderma harzianum induces maize resistance to Curvularia lunata through the jasmonic acid signaling pathway.

PubMed

Yu, Chuanjin; Fan, Lili; Gao, Jinxin; Wang, Meng; Wu, Qiong; Tang, Jun; Li, Yaqian; Chen, Jie

2015-01-01

Platelet-activating factor acetylhydrolase (PAF-AH) derived from Trichoderma harzianum was upregulated by the interaction of T. harzianum with maize roots or the foliar pathogen Curvularia lunata. PAF-AH was associated with chitinase and cellulase expressions, but especially with chitinase, because its activity in the KO40 transformant (PAF-AH disruption transformant) was lower, compared with the wild-type strain T28. The result demonstrated that the colonization of maize roots by T. harzianum induced systemic protection of leaves inoculated with C. lunata. Such protection was associated with the expression of inducible jasmonic acid pathway-related genes. Moreover, the data from liquid chromatography-mass spectrometry confirmed that the concentration of jasmonic acid in maize leaves was associated with the expression level of defense-related genes, suggesting that PAF-AH induced resistance to the foliar pathogen. Our findings showed that PAF-AH had an important function in inducing systemic resistance to maize leaf spot pathogen.
Analyses of Catharanthus roseus and Arabidopsis thaliana WRKY transcription factors reveal involvement in jasmonate signaling.

PubMed

Schluttenhofer, Craig; Pattanaik, Sitakanta; Patra, Barunava; Yuan, Ling

2014-06-20

To combat infection to biotic stress plants elicit the biosynthesis of numerous natural products, many of which are valuable pharmaceutical compounds. Jasmonate is a central regulator of defense response to pathogens and accumulation of specialized metabolites. Catharanthus roseus produces a large number of terpenoid indole alkaloids (TIAs) and is an excellent model for understanding the regulation of this class of valuable compounds. Recent work illustrates a possible role for the Catharanthus WRKY transcription factors (TFs) in regulating TIA biosynthesis. In Arabidopsis and other plants, the WRKY TF family is also shown to play important role in controlling tolerance to biotic and abiotic stresses, as well as secondary metabolism. Here, we describe the WRKY TF families in response to jasmonate in Arabidopsis and Catharanthus. Publically available Arabidopsis microarrays revealed at least 30% (22 of 72) of WRKY TFs respond to jasmonate treatments. Microarray analysis identified at least six jasmonate responsive Arabidopsis WRKY genes (AtWRKY7, AtWRKY20, AtWRKY26, AtWRKY45, AtWRKY48, and AtWRKY72) that have not been previously reported. The Catharanthus WRKY TF family is comprised of at least 48 members. Phylogenetic clustering reveals 11 group I, 32 group II, and 5 group III WRKY TFs. Furthermore, we found that at least 25% (12 of 48) were jasmonate responsive, and 75% (9 of 12) of the jasmonate responsive CrWRKYs are orthologs of AtWRKYs known to be regulated by jasmonate. Overall, the CrWRKY family, ascertained from transcriptome sequences, contains approximately 75% of the number of WRKYs found in other sequenced asterid species (pepper, tomato, potato, and bladderwort). Microarray and transcriptomic data indicate that expression of WRKY TFs in Arabidopsis and Catharanthus are under tight spatio-temporal and developmental control, and potentially have a significant role in jasmonate signaling. Profiling of CrWRKY expression in response to jasmonate treatment
Priming of jasmonate-mediated anti-herbivore defense responses in rice by silicon

USDA-ARS?s Scientific Manuscript database

While the function of silicon (Si) in plant physiology has long been debated, its beneficial effects on plant resistance against abiotic and biotic stresses, ¬including insect herbivory, have been well-documented. In addition, the jasmonate (JA) signaling pathway plays a crucial role in mediating an...
The SAL-PAP Chloroplast Retrograde Pathway Contributes to Plant Immunity by Regulating Glucosinolate Pathway and Phytohormone Signaling.

PubMed

Ishiga, Yasuhiro; Watanabe, Mutsumi; Ishiga, Takako; Tohge, Takayuki; Matsuura, Takakazu; Ikeda, Yoko; Hoefgen, Rainer; Fernie, Alisdair R; Mysore, Kirankumar S

2017-10-01

Chloroplasts have a crucial role in plant immunity against pathogens. Increasing evidence suggests that phytopathogens target chloroplast homeostasis as a pathogenicity mechanism. In order to regulate the performance of chloroplasts under stress conditions, chloroplasts produce retrograde signals to alter nuclear gene expression. Many signals for the chloroplast retrograde pathway have been identified, including chlorophyll intermediates, reactive oxygen species, and metabolic retrograde signals. Although there is a reasonably good understanding of chloroplast retrograde signaling in plant immunity, some signals are not well-understood. In order to understand the role of chloroplast retrograde signaling in plant immunity, we investigated Arabidopsis chloroplast retrograde signaling mutants in response to pathogen inoculation. sal1 mutants (fry1-2 and alx8) responsible for the SAL1-PAP retrograde signaling pathway showed enhanced disease symptoms not only to the hemibiotrophic pathogen Pseudomonas syringae pv. tomato DC3000 but, also, to the necrotrophic pathogen Pectobacterium carotovorum subsp. carotovorum EC1. Glucosinolate profiles demonstrated the reduced accumulation of aliphatic glucosinolates in the fry1-2 and alx8 mutants compared with the wild-type Col-0 in response to DC3000 infection. In addition, quantification of multiple phytohormones and analyses of their gene expression profiles revealed that both the salicylic acid (SA)- and jasmonic acid (JA)-mediated signaling pathways were down-regulated in the fry1-2 and alx8 mutants. These results suggest that the SAL1-PAP chloroplast retrograde pathway is involved in plant immunity by regulating the SA- and JA-mediated signaling pathways.
Distinct Roles of Jasmonates and Aldehydes in Plant-Defense Responses

PubMed Central

Chehab, E. Wassim; Kaspi, Roy; Savchenko, Tatyana; Rowe, Heather; Negre-Zakharov, Florence; Kliebenstein, Dan; Dehesh, Katayoon

2008-01-01

Background Many inducible plant-defense responses are activated by jasmonates (JAs), C6-aldehydes, and their corresponding derivatives, produced by the two main competing branches of the oxylipin pathway, the allene oxide synthase (AOS) and hydroperoxide lyase (HPL) branches, respectively. In addition to competition for substrates, these branch-pathway-derived metabolites have substantial overlap in regulation of gene expression. Past experiments to define the role of C6-aldehydes in plant defense responses were biased towards the exogenous application of the synthetic metabolites or the use of genetic manipulation of HPL expression levels in plant genotypes with intact ability to produce the competing AOS-derived metabolites. To uncouple the roles of the C6-aldehydes and jasmonates in mediating direct and indirect plant-defense responses, we generated Arabidopsis genotypes lacking either one or both of these metabolites. These genotypes were subsequently challenged with a phloem-feeding insect (aphids: Myzus persicae), an insect herbivore (leafminers: Liriomyza trifolii), and two different necrotrophic fungal pathogens (Botrytis cinerea and Alternaria brassicicola). We also characterized the volatiles emitted by these plants upon aphid infestation or mechanical wounding and identified hexenyl acetate as the predominant compound in these volatile blends. Subsequently, we examined the signaling role of this compound in attracting the parasitoid wasp (Aphidius colemani), a natural enemy of aphids. Principal Findings This study conclusively establishes that jasmonates and C6-aldehydes play distinct roles in plant defense responses. The jasmonates are indispensable metabolites in mediating the activation of direct plant-defense responses, whereas the C6-aldehyes are not. On the other hand, hexenyl acetate, an acetylated C6-aldehyde, is the predominant wound-inducible volatile signal that mediates indirect defense responses by directing tritrophic (plant
Activation of the Jasmonic Acid Pathway by Depletion of the Hydroperoxide Lyase OsHPL3 Reveals Crosstalk between the HPL and AOS Branches of the Oxylipin Pathway in Rice

PubMed Central

Tang, Jiuyou; Wang, Weihong; Zhang, Fengxia; Wang, Guodong; Chu, Jinfang; Yan, Cunyu; Wang, Taoqing; Chu, Chengcai; Li, Chuanyou

2012-01-01

The allene oxide synthase (AOS) and hydroperoxide lyase (HPL) branches of the oxylipin pathway, which underlie the production of jasmonates and aldehydes, respectively, function in plant responses to a range of stresses. Regulatory crosstalk has been proposed to exist between these two signaling branches; however, there is no direct evidence of this. Here, we identified and characterized a jasmonic acid (JA) overproduction mutant, cea62, by screening a rice T-DNA insertion mutant library for lineages that constitutively express the AOS gene. Map-based cloning was used to identify the underlying gene as hydroperoxide lyase OsHPL3. HPL3 expression and the enzyme activity of its product, (E)-2-hexenal, were depleted in the cea62 mutant, which resulted in the dramatic overproduction of JA, the activation of JA signaling, and the emergence of the lesion mimic phenotype. A time-course analysis of lesion formation and of the induction of defense responsive genes in the cea62 mutant revealed that the activation of JA biosynthesis and signaling in cea62 was regulated in a developmental manner, as was OsHPL3 activity in the wild-type plant. Microarray analysis showed that the JA-governed defense response was greatly activated in cea62 and this plant exhibited enhanced resistance to the T1 strain of the bacterial blight pathogen Xanthomonasoryzaepvoryzae (Xoo). The wounding response was attenuated in cea62 plants during the early stages of development, but partially recovered when JA levels were elevated during the later stages. In contrast, the wounding response was not altered during the different developmental stages of wild-type plants. These findings suggest that these two branches of the oxylipin pathway exhibit crosstalk with regards to biosynthesis and signaling and cooperate with each other to function in diverse stress responses. PMID:23209649
Structural insights into alternative splicing-mediated desensitization of jasmonate signaling.

PubMed

Zhang, Feng; Ke, Jiyuan; Zhang, Li; Chen, Rongzhi; Sugimoto, Koichi; Howe, Gregg A; Xu, H Eric; Zhou, Mingguo; He, Sheng Yang; Melcher, Karsten

2017-02-14

Jasmonate ZIM-domain (JAZ) transcriptional repressors play a key role in regulating jasmonate (JA) signaling in plants. Below a threshold concentration of jasmonoyl isoleucine (JA-Ile), the active form of JA, the C-terminal Jas motif of JAZ proteins binds MYC transcription factors to repress JA signaling. With increasing JA-Ile concentration, the Jas motif binds to JA-Ile and the COI1 subunit of the SCF COI1 E3 ligase, which mediates ubiquitination and proteasomal degradation of JAZ repressors, resulting in derepression of MYC transcription factors. JA signaling subsequently becomes desensitized, in part by feedback induction of JAZ splice variants that lack the C-terminal Jas motif but include an N-terminal cryptic MYC-interaction domain (CMID). The CMID sequence is dissimilar to the Jas motif and is incapable of recruiting SCF COI1 , allowing CMID-containing JAZ splice variants to accumulate in the presence of JA and to re-repress MYC transcription factors as an integral part of reestablishing signal homeostasis. The mechanism by which the CMID represses MYC transcription factors remains elusive. Here we describe the crystal structure of the MYC3-CMID JAZ10 complex. In contrast to the Jas motif, which forms a single continuous helix when bound to MYC3, the CMID adopts a loop-helix-loop-helix architecture with modular interactions with both the Jas-binding groove and the backside of the Jas-interaction domain of MYC3. This clamp-like interaction allows the CMID to bind MYC3 tightly and block access of MED25 (a subunit of the Mediator coactivator complex) to the MYC3 transcriptional activation domain, shedding light on the enigmatic mechanism by which JAZ splice variants desensitize JA signaling.
Arabidopsis GLUTATHIONE REDUCTASE1 plays a crucial role in leaf responses to intracellular hydrogen peroxide and in ensuring appropriate gene expression through both salicylic acid and jasmonic acid signaling pathways.

PubMed

Mhamdi, Amna; Hager, Jutta; Chaouch, Sejir; Queval, Guillaume; Han, Yi; Taconnat, Ludivine; Saindrenan, Patrick; Gouia, Houda; Issakidis-Bourguet, Emmanuelle; Renou, Jean-Pierre; Noctor, Graham

2010-07-01

Glutathione is a major cellular thiol that is maintained in the reduced state by glutathione reductase (GR), which is encoded by two genes in Arabidopsis (Arabidopsis thaliana; GR1 and GR2). This study addressed the role of GR1 in hydrogen peroxide (H(2)O(2)) responses through a combined genetic, transcriptomic, and redox profiling approach. To identify the potential role of changes in glutathione status in H(2)O(2) signaling, gr1 mutants, which show a constitutive increase in oxidized glutathione (GSSG), were compared with a catalase-deficient background (cat2), in which GSSG accumulation is conditionally driven by H(2)O(2). Parallel transcriptomics analysis of gr1 and cat2 identified overlapping gene expression profiles that in both lines were dependent on growth daylength. Overlapping genes included phytohormone-associated genes, in particular implicating glutathione oxidation state in the regulation of jasmonic acid signaling. Direct analysis of H(2)O(2)-glutathione interactions in cat2 gr1 double mutants established that GR1-dependent glutathione status is required for multiple responses to increased H(2)O(2) availability, including limitation of lesion formation, accumulation of salicylic acid, induction of pathogenesis-related genes, and signaling through jasmonic acid pathways. Modulation of these responses in cat2 gr1 was linked to dramatic GSSG accumulation and modified expression of specific glutaredoxins and glutathione S-transferases, but there is little or no evidence of generalized oxidative stress or changes in thioredoxin-associated gene expression. We conclude that GR1 plays a crucial role in daylength-dependent redox signaling and that this function cannot be replaced by the second Arabidopsis GR gene or by thiol systems such as the thioredoxin system.
Salicylic acid suppresses jasmonic acid signaling downstream of SCFCOI1-JAZ by targeting GCC promoter motifs via transcription factor ORA59.

PubMed

Van der Does, Dieuwertje; Leon-Reyes, Antonio; Koornneef, Annemart; Van Verk, Marcel C; Rodenburg, Nicole; Pauwels, Laurens; Goossens, Alain; Körbes, Ana P; Memelink, Johan; Ritsema, Tita; Van Wees, Saskia C M; Pieterse, Corné M J

2013-02-01

Antagonism between the defense hormones salicylic acid (SA) and jasmonic acid (JA) plays a central role in the modulation of the plant immune signaling network, but the molecular mechanisms underlying this phenomenon are largely unknown. Here, we demonstrate that suppression of the JA pathway by SA functions downstream of the E3 ubiquitin-ligase Skip-Cullin-F-box complex SCF(COI1), which targets JASMONATE ZIM-domain transcriptional repressor proteins (JAZs) for proteasome-mediated degradation. In addition, neither the stability nor the JA-induced degradation of JAZs was affected by SA. In silico promoter analysis of the SA/JA crosstalk transcriptome revealed that the 1-kb promoter regions of JA-responsive genes that are suppressed by SA are significantly enriched in the JA-responsive GCC-box motifs. Using GCC:GUS lines carrying four copies of the GCC-box fused to the β-glucuronidase reporter gene, we showed that the GCC-box motif is sufficient for SA-mediated suppression of JA-responsive gene expression. Using plants overexpressing the GCC-box binding APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) transcription factors ERF1 or ORA59, we found that SA strongly reduces the accumulation of ORA59 but not that of ERF1. Collectively, these data indicate that the SA pathway inhibits JA signaling downstream of the SCF(COI1)-JAZ complex by targeting GCC-box motifs in JA-responsive promoters via a negative effect on the transcriptional activator ORA59.
Necrotrophic pathogens use the salicylic acid signaling pathway to promote disease development in tomato.

PubMed

Rahman, Taha Abd El; Oirdi, Mohamed El; Gonzalez-Lamothe, Rocio; Bouarab, Kamal

2012-12-01

Plants use different immune pathways to combat pathogens. The activation of the jasmonic acid (JA)-signaling pathway is required for resistance against necrotrophic pathogens; however, to combat biotrophic pathogens, the plants activate mainly the salicylic acid (SA)-signaling pathway. SA can antagonize JA signaling and vice versa. NPR1 (noninducible pathogenesis-related 1) is considered a master regulator of SA signaling. NPR1 interacts with TGA transcription factors, ultimately leading to the activation of SA-dependent responses. SA has been shown to promote disease development caused by the necrotrophic pathogen Botrytis cinerea through NPR1, by suppressing the expression of two JA-dependent defense genes, proteinase inhibitors I and II. We show here that the transcription factor TGA1.a contributes to disease development caused by B. cinerea in tomato by suppressing the expression of proteinase inhibitors I and II. Finally, we present evidence that the SA-signaling pathway contributes to disease development caused by another necrotrophic pathogen, Alternaria solani, in tomato. Disease development promoted by SA through NPR1 requires the TGA1.a transcription factor. These data highlight how necrotrophs manipulate the SAsignaling pathway to promote their disease in tomato.
O-GlcNAcylation of master growth repressor DELLA by SECRET AGENT modulates multiple signaling pathways in Arabidopsis

PubMed Central

Zentella, Rodolfo; Hu, Jianhong; Hsieh, Wen-Ping; Matsumoto, Peter A.; Dawdy, Andrew; Barnhill, Benjamin; Oldenhof, Harriëtte; Hartweck, Lynn M.; Maitra, Sushmit; Thomas, Stephen G.; Cockrell, Shelley; Boyce, Michael; Shabanowitz, Jeffrey; Hunt, Donald F.; Olszewski, Neil E.; Sun, Tai-ping

2016-01-01

The DELLA family of transcription regulators functions as master growth repressors in plants by inhibiting phytohormone gibberellin (GA) signaling in response to developmental and environmental cues. DELLAs also play a central role in mediating cross-talk between GA and other signaling pathways via antagonistic direct interactions with key transcription factors. However, how these crucial protein–protein interactions can be dynamically regulated during plant development remains unclear. Here, we show that DELLAs are modified by the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis. O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors—PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)—that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. Consistent with this, the sec-null mutant displayed reduced responses to GA and brassinosteroid and showed decreased expression of several common target genes of DELLAs, BZR1, and PIFs. Our results reveal a direct role of OGT in repressing DELLA activity and indicate that O-GlcNAcylation of DELLAs provides a fine-tuning mechanism in coordinating multiple signaling activities during plant development. PMID:26773002
O-GlcNAcylation of master growth repressor DELLA by SECRET AGENT modulates multiple signaling pathways in Arabidopsis.

PubMed

Zentella, Rodolfo; Hu, Jianhong; Hsieh, Wen-Ping; Matsumoto, Peter A; Dawdy, Andrew; Barnhill, Benjamin; Oldenhof, Harriëtte; Hartweck, Lynn M; Maitra, Sushmit; Thomas, Stephen G; Cockrell, Shelley; Boyce, Michael; Shabanowitz, Jeffrey; Hunt, Donald F; Olszewski, Neil E; Sun, Tai-Ping

2016-01-15

The DELLA family of transcription regulators functions as master growth repressors in plants by inhibiting phytohormone gibberellin (GA) signaling in response to developmental and environmental cues. DELLAs also play a central role in mediating cross-talk between GA and other signaling pathways via antagonistic direct interactions with key transcription factors. However, how these crucial protein-protein interactions can be dynamically regulated during plant development remains unclear. Here, we show that DELLAs are modified by the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis. O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. Consistent with this, the sec-null mutant displayed reduced responses to GA and brassinosteroid and showed decreased expression of several common target genes of DELLAs, BZR1, and PIFs. Our results reveal a direct role of OGT in repressing DELLA activity and indicate that O-GlcNAcylation of DELLAs provides a fine-tuning mechanism in coordinating multiple signaling activities during plant development. © 2016 Zentella et al.; Published by Cold Spring Harbor Laboratory Press.
Deficiencies in Jasmonate-Mediated Plant Defense Reveal Quantitative Variation in Botrytis cinerea Pathogenesis

PubMed Central

Rowe, Heather C.; Walley, Justin W.; Corwin, Jason; Chan, Eva K.-F.; Dehesh, Katayoon; Kliebenstein, Daniel J.

2010-01-01

Despite the described central role of jasmonate signaling in plant defense against necrotrophic pathogens, the existence of intraspecific variation in pathogen capacity to activate or evade plant jasmonate-mediated defenses is rarely considered. Experimental infection of jasmonate-deficient and jasmonate-insensitive Arabidopsis thaliana with diverse isolates of the necrotrophic fungal pathogen Botrytis cinerea revealed pathogen variation for virulence inhibition by jasmonate-mediated plant defenses and induction of plant defense metabolites. Comparison of the transcriptional effects of infection by two distinct B. cinerea isolates showed only minor differences in transcriptional responses of wild-type plants, but notable isolate-specific transcript differences in jasmonate-insensitive plants. These transcriptional differences suggest B. cinerea activation of plant defenses that require plant jasmonate signaling for activity in response to only one of the two B. cinerea isolates tested. Thus, similar infection phenotypes observed in wild-type plants result from different signaling interactions with the plant that are likely integrated by jasmonate signaling. PMID:20419157

Multiple phytohormone signalling pathways modulate susceptibility of tomato plants to Alternaria alternata f. sp. lycopersici

PubMed Central

Jia, Chengguo; Zhang, Liping; Wang, Qiaomei

2013-01-01

Three phytohormone molecules – ethylene (ET), jasmonic acid (JA) and salicylic acid (SA) – play key roles in mediating disease response to necrotrophic fungal pathogens. This study investigated the roles of the ET, JA, and SA pathways as well as their crosstalk during the interaction between tomato (Solanum lycopersicum) plants and a necrotrophic fungal pathogen Alternaria alternata f. sp. lycopersici (AAL). Both the ET and JASMONIC ACID INSENSITIVE1 (JAI1) receptor-dependent JA signalling pathways are necessary for susceptibility, while SA response promotes resistance to AAL infection. In addition, the role of JA in susceptibility to AAL is partly dependent on ET biosynthesis and perception, while the SA pathway enhances resistance to AAL and antagonizes the ET response. Based on these results, it is proposed that ET, JA, and SA each on their own can influence the susceptibility of tomato to AAL. Furthermore, the functions of JA and SA in susceptibility to the pathogen are correlated with the enhanced or decreased action of ET, respectively. This study has revealed the functional relationship among the three key hormone pathways in tomato defence against AAL. PMID:23264518
Lipoxygenase in Caragana jubata responds to low temperature, abscisic acid, methyl jasmonate and salicylic acid.

PubMed

Bhardwaj, Pardeep Kumar; Kaur, Jagdeep; Sobti, Ranbir Chander; Ahuja, Paramvir Singh; Kumar, Sanjay

2011-09-01

Lipoxygenase (LOX) catalyses oxygenation of free polyunsaturated fatty acids into oxylipins, and is a critical enzyme of the jasmonate signaling pathway. LOX has been shown to be associated with biotic and abiotic stress responses in diverse plant species, though limited data is available with respect to low temperature and the associated cues. Using rapid amplification of cDNA ends, a full-length cDNA (CjLOX) encoding lipoxygenase was cloned from apical buds of Caragana jubata, a temperate plant species that grows under extreme cold. The cDNA obtained was 2952bp long consisting of an open reading frame of 2610bp encoding 869 amino acids protein. Multiple alignment of the deduced amino acid sequence with those of other plants demonstrated putative LH2/ PLAT domain, lipoxygenase iron binding catalytic domain and lipoxygenase_2 signature sequences. CjLOX exhibited up- and down-regulation of gene expression pattern in response to low temperature (LT), abscisic acid (ABA), methyl jasmonate (MJ) and salicylic acid (SA). Among all the treatments, a strong up-regulation was observed in response to MJ. Data suggests an important role of jasmonate signaling pathway in response to LT in C. jubata. Copyright © 2011 Elsevier B.V. All rights reserved.
Jasmonates induce both defense responses and communication in monocotyledonous and dicotyledonous plants.

PubMed

Okada, Kazunori; Abe, Hiroshi; Arimura, Gen-ichiro

2015-01-01

Jasmonic acid (JA) and its derivatives (jasmonates, JAs) are phytohormones with essential roles in plant defense against pathogenesis and herbivorous arthropods. Both the up- and down-regulation of defense responses are dependent on signaling pathways mediated by JAs as well as other stress hormones (e.g. salicylic acid), generally those involving the transcriptional and post-transcriptional regulation of transcription factors via protein modification and epigenetic regulation. In addition to the typical model plant Arabidopsis (a dicotyledon), advances in genetics research have made rice a model monocot in which innovative pest control traits can be introduced and whose JA signaling pathway can be studied. In this review, we introduce the dynamic functions of JAs in plant defense strategy using defensive substances (e.g. indole alkaloids and terpenoid phytoalexins) and airborne signals (e.g. green leaf volatiles and volatile terpenes) in response to biotrophic and necrotrophic pathogens as well as above-ground and below-ground herbivores. We then discuss the important issue of how the mutualism of herbivorous arthropods with viruses or bacteria can cause cross-talk between JA and other phytohormones to counter the defense systems. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.
UV-C-Induced alleviation of transcriptional gene silencing through plant-plant communication: Key roles of jasmonic acid and salicylic acid pathways.

PubMed

Xu, Wei; Wang, Ting; Xu, Shaoxin; Li, Fanghua; Deng, Chenguang; Wu, Lijun; Wu, Yuejin; Bian, Po

2016-08-01

Plant stress responses at the epigenetic level are expected to allow more permanent changes of gene expression and potentially long-term adaptation. While it has been reported that plants subjected to adverse environments initiate various stress responses in their neighboring plants, little is known regarding epigenetic responses to external stresses mediated by plant-plant communication. In this study, we show that DNA repetitive elements of Arabidopsis thaliana, whose expression is inhibited epigenetically by transcriptional gene silencing (TGS) mechanism, are activated by UV-C irradiation through airborne plant-plant and plant-plant-plant communications, accompanied by DNA demethylation at CHH sites. Moreover, the TGS is alleviated by direct treatments with exogenous methyl jasmonate (MeJA) and methyl salicylate (MeSA). Further, the plant-plant and plant-plant-plant communications are blocked by mutations in the biosynthesis or signaling of jasmonic acid (JA) or salicylic acid (SA), indicating that JA and SA pathways are involved in the interplant communication for epigenetic responses. For the plant-plant-plant communication, stress cues are relayed to the last set of receiver plants by promoting the production of JA and SA signals in relaying plants, which exhibit upregulated expression of genes for JA and SA biosynthesis and enhanced emanation of MeJA and MeSA. Copyright © 2016 Elsevier B.V. All rights reserved.
Roles of jasmonate signalling in plant inflorescence and flower development.

PubMed

Yuan, Zheng; Zhang, Dabing

2015-10-01

Development of inflorescences and flowers in plants is controlled by the combined action of environmental and genetic signals. Investigations reveal that the phytohormone jasmonate (JA) plays a critical function in plant reproduction such as male fertility, sex determination and seed maturation. Here, we review recent progress on JA synthesis, signalling, the interplay between JAs and other hormones, and regulatory network of JA in controlling the development of inflorescence, flower and the male organ. The conserved and diversified roles of JAs in meristem transition and specification of flower organ identity and number, and multiple regulatory networks of JAs in stamen development are highlighted. Further, this review provides perspectives on future research endeavors to elucidate mechanisms underlying JAs homeostasis and transport during plant reproductive development. Copyright © 2015 Elsevier Ltd. All rights reserved.
Induced jasmonate signaling leads to contrasting effects on root damage and herbivore performance.

PubMed

Lu, Jing; Robert, Christelle Aurélie Maud; Riemann, Michael; Cosme, Marco; Mène-Saffrané, Laurent; Massana, Josep; Stout, Michael Joseph; Lou, Yonggen; Gershenzon, Jonathan; Erb, Matthias

2015-03-01

Induced defenses play a key role in plant resistance against leaf feeders. However, very little is known about the signals that are involved in defending plants against root feeders and how they are influenced by abiotic factors. We investigated these aspects for the interaction between rice (Oryza sativa) and two root-feeding insects: the generalist cucumber beetle (Diabrotica balteata) and the more specialized rice water weevil (Lissorhoptrus oryzophilus). Rice plants responded to root attack by increasing the production of jasmonic acid (JA) and abscisic acid, whereas in contrast to in herbivore-attacked leaves, salicylic acid and ethylene levels remained unchanged. The JA response was decoupled from flooding and remained constant over different soil moisture levels. Exogenous application of methyl JA to the roots markedly decreased the performance of both root herbivores, whereas abscisic acid and the ethylene precursor 1-aminocyclopropane-1-carboxylic acid did not have any effect. JA-deficient antisense 13-lipoxygenase (asLOX) and mutant allene oxide cyclase hebiba plants lost more root biomass under attack from both root herbivores. Surprisingly, herbivore weight gain was decreased markedly in asLOX but not hebiba mutant plants, despite the higher root biomass removal. This effect was correlated with a herbivore-induced reduction of sucrose pools in asLOX roots. Taken together, our experiments show that jasmonates are induced signals that protect rice roots from herbivores under varying abiotic conditions and that boosting jasmonate responses can strongly enhance rice resistance against root pests. Furthermore, we show that a rice 13-lipoxygenase regulates root primary metabolites and specifically improves root herbivore growth. © 2015 American Society of Plant Biologists. All Rights Reserved.
Salicylic Acid Suppresses Jasmonic Acid Signaling Downstream of SCFCOI1-JAZ by Targeting GCC Promoter Motifs via Transcription Factor ORA59[C][W][OA

PubMed Central

Van der Does, Dieuwertje; Leon-Reyes, Antonio; Koornneef, Annemart; Van Verk, Marcel C.; Rodenburg, Nicole; Pauwels, Laurens; Goossens, Alain; Körbes, Ana P.; Memelink, Johan; Ritsema, Tita; Van Wees, Saskia C.M.; Pieterse, Corné M.J.

2013-01-01

Antagonism between the defense hormones salicylic acid (SA) and jasmonic acid (JA) plays a central role in the modulation of the plant immune signaling network, but the molecular mechanisms underlying this phenomenon are largely unknown. Here, we demonstrate that suppression of the JA pathway by SA functions downstream of the E3 ubiquitin-ligase Skip-Cullin-F-box complex SCFCOI1, which targets JASMONATE ZIM-domain transcriptional repressor proteins (JAZs) for proteasome-mediated degradation. In addition, neither the stability nor the JA-induced degradation of JAZs was affected by SA. In silico promoter analysis of the SA/JA crosstalk transcriptome revealed that the 1-kb promoter regions of JA-responsive genes that are suppressed by SA are significantly enriched in the JA-responsive GCC-box motifs. Using GCC:GUS lines carrying four copies of the GCC-box fused to the β-glucuronidase reporter gene, we showed that the GCC-box motif is sufficient for SA-mediated suppression of JA-responsive gene expression. Using plants overexpressing the GCC-box binding APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) transcription factors ERF1 or ORA59, we found that SA strongly reduces the accumulation of ORA59 but not that of ERF1. Collectively, these data indicate that the SA pathway inhibits JA signaling downstream of the SCFCOI1-JAZ complex by targeting GCC-box motifs in JA-responsive promoters via a negative effect on the transcriptional activator ORA59. PMID:23435661
Arabidopsis GLUTATHIONE REDUCTASE1 Plays a Crucial Role in Leaf Responses to Intracellular Hydrogen Peroxide and in Ensuring Appropriate Gene Expression through Both Salicylic Acid and Jasmonic Acid Signaling Pathways1[C][W][OA

PubMed Central

Mhamdi, Amna; Hager, Jutta; Chaouch, Sejir; Queval, Guillaume; Han, Yi; Taconnat, Ludivine; Saindrenan, Patrick; Gouia, Houda; Issakidis-Bourguet, Emmanuelle; Renou, Jean-Pierre; Noctor, Graham

2010-01-01

Glutathione is a major cellular thiol that is maintained in the reduced state by glutathione reductase (GR), which is encoded by two genes in Arabidopsis (Arabidopsis thaliana; GR1 and GR2). This study addressed the role of GR1 in hydrogen peroxide (H2O2) responses through a combined genetic, transcriptomic, and redox profiling approach. To identify the potential role of changes in glutathione status in H2O2 signaling, gr1 mutants, which show a constitutive increase in oxidized glutathione (GSSG), were compared with a catalase-deficient background (cat2), in which GSSG accumulation is conditionally driven by H2O2. Parallel transcriptomics analysis of gr1 and cat2 identified overlapping gene expression profiles that in both lines were dependent on growth daylength. Overlapping genes included phytohormone-associated genes, in particular implicating glutathione oxidation state in the regulation of jasmonic acid signaling. Direct analysis of H2O2-glutathione interactions in cat2 gr1 double mutants established that GR1-dependent glutathione status is required for multiple responses to increased H2O2 availability, including limitation of lesion formation, accumulation of salicylic acid, induction of pathogenesis-related genes, and signaling through jasmonic acid pathways. Modulation of these responses in cat2 gr1 was linked to dramatic GSSG accumulation and modified expression of specific glutaredoxins and glutathione S-transferases, but there is little or no evidence of generalized oxidative stress or changes in thioredoxin-associated gene expression. We conclude that GR1 plays a crucial role in daylength-dependent redox signaling and that this function cannot be replaced by the second Arabidopsis GR gene or by thiol systems such as the thioredoxin system. PMID:20488891
Jasmonate action in plant growth and development.

PubMed

Huang, Huang; Liu, Bei; Liu, Liangyu; Song, Susheng

2017-03-01

Phytohormones, including jasmonates (JAs), gibberellin, ethylene, abscisic acid, and auxin, integrate endogenous developmental cues with environmental signals to regulate plant growth, development, and defense. JAs are well- recognized lipid-derived stress hormones that regulate plant adaptations to biotic stresses, including herbivore attack and pathogen infection, as well as abiotic stresses, including wounding, ozone, and ultraviolet radiation. An increasing number of studies have shown that JAs also have functions in a remarkable number of plant developmental events, including primary root growth, reproductive development, and leaf senescence. Since the 1980s, details of the JA biosynthesis pathway, signaling pathway, and crosstalk during plant growth and development have been elucidated. Here, we summarize recent advances and give an updated overview of JA action and crosstalk in plant growth and development. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Meristem maintenance, auxin, jasmonic and abscisic acid pathways as a mechanism for phenotypic plasticity in Antirrhinum majus

NASA Astrophysics Data System (ADS)

Weiss, Julia; Alcantud-Rodriguez, Raquel; Toksöz, Tugba; Egea-Cortines, Marcos

2016-01-01

Plants grow under climatic changing conditions that cause modifications in vegetative and reproductive development. The degree of changes in organ development i.e. its phenotypic plasticity seems to be determined by the organ identity and the type of environmental cue. We used intraspecific competition and found that Antirrhinum majus behaves as a decoupled species for lateral organ size and number. Crowding causes decreases in leaf size and increased leaf number whereas floral size is robust and floral number is reduced. Genes involved in shoot apical meristem maintenance like ROA and HIRZ, cell cycle (CYCD3a; CYCD3b, HISTONE H4) or organ polarity (GRAM) were not significantly downregulated under crowding conditions. A transcriptomic analysis of inflorescence meristems showed Gene Ontology enriched pathways upregulated including Jasmonic and Abscisic acid synthesis and or signalling. Genes involved in auxin synthesis such as AmTAR2 and signalling AmANT were not affected by crowding. In contrast, AmJAZ1, AmMYB21, AmOPCL1 and AmABA2 were significantly upregulated. Our work provides a mechanistic working hypothesis where a robust SAM and stable auxin signalling enables a homogeneous floral size while changes in JA and ABA signalling maybe responsible for the decreased leaf size and floral number.
Constitutive activation of jasmonate signaling in an Arabidopsis mutant correlates with enhanced resistance to Erysiphe cichoracearum, Pseudomonas syringae, and Myzus persicae.

PubMed

Ellis, Christine; Karafyllidis, Ioannis; Turner, John G

2002-10-01

In Arabidopsis spp., the jasmonate (JA) response pathway generally is required for defenses against necrotrophic pathogens and chewing insects, while the salicylic acid (SA) response pathway is generally required for specific, resistance (R) gene-mediated defenses against both biotrophic and necrotrophic pathogens. For example, SA-dependent defenses are required for resistance to the biotrophic fungal pathogen Erysiphe cichoracearum UCSC1 and the bacterial pathogen Pseudomonas syringae pv. maculicola, and also are expressed during response to the green peach aphid Myzus persicae. However, recent evidence indicates that the expression of JA-dependent defenses also may confer resistance to E. cichoracearum. To confirm and to extend this observation, we have compared the disease and pest resistance of wild-type Arabidopsis plants with that of the mutants coil, which is insensitive to JA, and cev1, which has constitutive JA signaling. Measurements of the colonization of these plants by E. cichoracearum, P. syringae pv. maculicola, and M. persicae indicated that activation of the JA signal pathway enhanced resistance, and was associated with the activation of JA-dependent defense genes and the suppression of SA-dependent defense genes. We conclude that JA and SA induce alternative defense pathways that can confer resistance to the same pathogens and pests.
Induced Jasmonate Signaling Leads to Contrasting Effects on Root Damage and Herbivore Performance1

PubMed Central

Lu, Jing; Robert, Christelle Aurélie Maud; Riemann, Michael; Cosme, Marco; Mène-Saffrané, Laurent; Massana, Josep; Stout, Michael Joseph; Lou, Yonggen; Gershenzon, Jonathan; Erb, Matthias

2015-01-01

Induced defenses play a key role in plant resistance against leaf feeders. However, very little is known about the signals that are involved in defending plants against root feeders and how they are influenced by abiotic factors. We investigated these aspects for the interaction between rice (Oryza sativa) and two root-feeding insects: the generalist cucumber beetle (Diabrotica balteata) and the more specialized rice water weevil (Lissorhoptrus oryzophilus). Rice plants responded to root attack by increasing the production of jasmonic acid (JA) and abscisic acid, whereas in contrast to in herbivore-attacked leaves, salicylic acid and ethylene levels remained unchanged. The JA response was decoupled from flooding and remained constant over different soil moisture levels. Exogenous application of methyl JA to the roots markedly decreased the performance of both root herbivores, whereas abscisic acid and the ethylene precursor 1-aminocyclopropane-1-carboxylic acid did not have any effect. JA-deficient antisense 13-lipoxygenase (asLOX) and mutant allene oxide cyclase hebiba plants lost more root biomass under attack from both root herbivores. Surprisingly, herbivore weight gain was decreased markedly in asLOX but not hebiba mutant plants, despite the higher root biomass removal. This effect was correlated with a herbivore-induced reduction of sucrose pools in asLOX roots. Taken together, our experiments show that jasmonates are induced signals that protect rice roots from herbivores under varying abiotic conditions and that boosting jasmonate responses can strongly enhance rice resistance against root pests. Furthermore, we show that a rice 13-lipoxygenase regulates root primary metabolites and specifically improves root herbivore growth. PMID:25627217
Arabidopsis MYC Transcription Factors Are the Target of Hormonal Salicylic Acid/Jasmonic Acid Cross Talk in Response to Pieris brassicae Egg Extract1[OPEN

PubMed Central

Schmiesing, André; Gouhier-Darimont, Caroline

2016-01-01

Arabidopsis (Arabidopsis thaliana) plants recognize insect eggs and activate the salicylic acid (SA) pathway. As a consequence, expression of defense genes regulated by the jasmonic acid (JA) pathway is suppressed and larval performance is enhanced. Cross talk between defense signaling pathways is common in plant-pathogen interactions, but the molecular mechanism mediating this phenomenon is poorly understood. Here, we demonstrate that egg-induced SA/JA antagonism works independently of the APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) transcription factor ORA59, which controls the ERF branch of the JA pathway. In addition, treatment with egg extract did not enhance expression or stability of JASMONATE ZIM-domain transcriptional repressors, and SA/JA cross talk did not involve JASMONATE ASSOCIATED MYC2-LIKEs, which are negative regulators of the JA pathway. Investigating the stability of MYC2, MYC3, and MYC4, three basic helix-loop-helix transcription factors that additively control jasmonate-related defense responses, we found that egg extract treatment strongly diminished MYC protein levels in an SA-dependent manner. Furthermore, we identified WRKY75 as a novel and essential factor controlling SA/JA cross talk. These data indicate that insect eggs target the MYC branch of the JA pathway and uncover an unexpected modulation of SA/JA antagonism depending on the biological context in which the SA pathway is activated. PMID:26884488
Arabidopsis MYC Transcription Factors Are the Target of Hormonal Salicylic Acid/Jasmonic Acid Cross Talk in Response to Pieris brassicae Egg Extract.

PubMed

Schmiesing, André; Emonet, Aurélia; Gouhier-Darimont, Caroline; Reymond, Philippe

2016-04-01

Arabidopsis (Arabidopsis thaliana) plants recognize insect eggs and activate the salicylic acid (SA) pathway. As a consequence, expression of defense genes regulated by the jasmonic acid (JA) pathway is suppressed and larval performance is enhanced. Cross talk between defense signaling pathways is common in plant-pathogen interactions, but the molecular mechanism mediating this phenomenon is poorly understood. Here, we demonstrate that egg-induced SA/JA antagonism works independently of the APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) transcription factor ORA59, which controls the ERF branch of the JA pathway. In addition, treatment with egg extract did not enhance expression or stability of JASMONATE ZIM-domain transcriptional repressors, and SA/JA cross talk did not involve JASMONATE ASSOCIATED MYC2-LIKEs, which are negative regulators of the JA pathway. Investigating the stability of MYC2, MYC3, and MYC4, three basic helix-loop-helix transcription factors that additively control jasmonate-related defense responses, we found that egg extract treatment strongly diminished MYC protein levels in an SA-dependent manner. Furthermore, we identified WRKY75 as a novel and essential factor controlling SA/JA cross talk. These data indicate that insect eggs target the MYC branch of the JA pathway and uncover an unexpected modulation of SA/JA antagonism depending on the biological context in which the SA pathway is activated. © 2016 American Society of Plant Biologists. All Rights Reserved.
Feeding by whiteflies suppresses downstream jasmonic acid signaling by eliciting salicylic acid signaling.

PubMed

Zhang, Peng-Jun; Li, Wei-Di; Huang, Fang; Zhang, Jin-Ming; Xu, Fang-Cheng; Lu, Yao-Bin

2013-05-01

Phloem-feeding whiteflies in the species complex Bemisia tabaci cause extensive crop damage worldwide. One of the reasons for their "success" is their ability to suppress the effectual jasmonic acid (JA) defenses of the host plant. However, little is understood about the mechanisms underlying whitefly suppression of JA-regulated defenses. Here, we showed that the expression of salicylic acid (SA)-responsive genes (EDS1 and PR1) in Arabidopsis thaliana was significantly enhanced during feeding by whitefly nymphs. Whereas upstream JA-responsive genes (LOX2 and OPR3) also were induced, the downstream JA-responsive gene (VSP1) was repressed, i.e., whiteflies only suppressed downstream JA signaling. Gene-expression analyses with various Arabidopsis mutants, including NahG, npr-1, ein2-1, and dde2-2, revealed that SA signaling plays a key role in the suppression of downstream JA defenses by whitefly feeding. Assays confirmed that SA activation enhanced whitefly performance by suppressing downstream JA defenses.
Induction of DREB2A pathway with repression of E2F, jasmonic acid biosynthetic and photosynthesis pathways in cold acclimation-specific freeze-resistant wheat crown.

PubMed

Karki, Amrit; Horvath, David P; Sutton, Fedora

2013-03-01

Winter wheat lines can achieve cold acclimation (development of tolerance to freezing temperatures) and vernalization (delay in transition from vegetative to reproductive phase) in response to low non-freezing temperatures. To describe cold-acclimation-specific processes and pathways, we utilized cold acclimation transcriptomic data from two lines varying in freeze survival but not vernalization. These lines, designated freeze-resistant (FR) and freeze-susceptible (FS), were the source of crown tissue RNA. Well-annotated differentially expressed genes (p ≤ 0.005 and fold change ≥ 2 in response to 4 weeks cold acclimation) were used for gene ontology and pathway analysis. "Abiotic stimuli" was identified as the most enriched and unique for FR. Unique to FS was "cytoplasmic components." Pathway analysis revealed the "triacylglycerol degradation" pathway as significantly downregulated and common to both FR and FS. The most enriched of FR pathways was "neighbors of DREB2A," with the highest positive median fold change. The "13-LOX and 13-HPL" and the "E2F" pathways were enriched in FR only with a negative median fold change. The "jasmonic acid biosynthesis" pathway and four "photosynthetic-associated" pathways were enriched in both FR and FS but with a more negative median fold change in FR than in FS. A pathway unique to FS was "binding partners of LHCA1," which was enriched only in FS with a significant negative median fold change. We propose that the DREB2A, E2F, jasmonic acid biosynthesis, and photosynthetic pathways are critical for discrimination between cold-acclimated lines varying in freeze survival.
Jasmonate Regulates Plant Responses to Postsubmergence Reoxygenation through Transcriptional Activation of Antioxidant Synthesis1

PubMed Central

Dai, Yang-Shuo; Xie, Li-Juan; Yu, Lu-Jun; Zhou, Ying; Lai, Yong-Xia; Yang, Yi-Cong; Xu, Le; Chen, Qin-Fang

2017-01-01

Submergence induces hypoxia in plants; exposure to oxygen following submergence, termed reoxygenation, produces a burst of reactive oxygen species. The mechanisms of hypoxia sensing and signaling in plants have been well studied, but how plants respond to reoxygenation remains unclear. Here, we show that reoxygenation in Arabidopsis (Arabidopsis thaliana) involves rapid accumulation of jasmonates (JAs) and increased transcript levels of JA biosynthesis genes. Application of exogenous methyl jasmonate improved tolerance to reoxygenation in wild-type Arabidopsis; also, mutants deficient in JA biosynthesis and signaling were very sensitive to reoxygenation. Moreover, overexpression of the transcription factor gene MYC2 enhanced tolerance to posthypoxic stress, and myc2 knockout mutants showed increased sensitivity to reoxygenation, indicating that MYC2 functions as a key regulator in the JA-mediated reoxygenation response. MYC2 transcriptionally activates members of the VITAMIN C DEFECTIVE (VTC) and GLUTATHIONE SYNTHETASE (GSH) gene families, which encode rate-limiting enzymes in the ascorbate and glutathione synthesis pathways. Overexpression of VTC1 and GSH1 in the myc2-2 mutant suppressed the posthypoxic hypersensitive phenotype. The JA-inducible accumulation of antioxidants may alleviate oxidative damage caused by reoxygenation, improving plant survival after submergence. Taken together, our findings demonstrate that JA signaling interacts with the antioxidant pathway to regulate reoxygenation responses in Arabidopsis. PMID:28082717
Interactions between the jasmonic and salicylic acid pathway modulate the plant metabolome and affect herbivores of different feeding types.

PubMed

Schweiger, R; Heise, A-M; Persicke, M; Müller, C

2014-07-01

The phytohormones jasmonic acid (JA) and salicylic acid (SA) mediate induced plant defences and the corresponding pathways interact in a complex manner as has been shown on the transcript and proteine level. Downstream, metabolic changes are important for plant-herbivore interactions. This study investigated metabolic changes in leaf tissue and phloem exudates of Plantago lanceolata after single and combined JA and SA applications as well as consequences on chewing-biting (Heliothis virescens) and piercing-sucking (Myzus persicae) herbivores. Targeted metabolite profiling and untargeted metabolic fingerprinting uncovered different categories of plant metabolites, which were influenced in a specific manner, indicating points of divergence, convergence, positive crosstalk and pronounced mutual antagonism between the signaling pathways. Phytohormone-specific decreases of primary metabolite pool sizes in the phloem exudates may indicate shifts in sink-source relations, resource allocation, nutrient uptake or photosynthesis. Survival of both herbivore species was significantly reduced by JA and SA treatments. However, the combined application of JA and SA attenuated the negative effects at least against H. virescens suggesting that mutual antagonism between the JA and SA pathway may be responsible. Pathway interactions provide a great regulatory potential for the plant that allows triggering of appropriate defences when attacked by different antagonist species. © 2013 John Wiley & Sons Ltd.
Non-pathogenic rhizobacteria interfere with the attraction of parasitoids to aphid-induced plant volatiles via jasmonic acid signalling.

PubMed

Pineda, Ana; Soler, Roxina; Weldegergis, Berhane T; Shimwela, Mpoki M; VAN Loon, Joop J A; Dicke, Marcel

2013-02-01

Beneficial soil-borne microbes, such as mycorrhizal fungi or rhizobacteria, can affect the interactions of plants with aboveground insects at several trophic levels. While the mechanisms of interactions with herbivorous insects, that is, the second trophic level, are starting to be understood, it remains unknown how plants mediate the interactions between soil microbes and carnivorous insects, that is, the third trophic level. Using Arabidopsis thaliana Col-0 and the aphid Myzus persicae, we evaluate here the underlying mechanisms involved in the plant-mediated interaction between the non-pathogenic rhizobacterium Pseudomonas fluorescens and the parasitoid Diaeretiella rapae, by combining ecological, chemical and molecular approaches. Rhizobacterial colonization modifies the composition of the blend of herbivore-induced plant volatiles. The volatile blend from rhizobacteria-treated aphid-infested plants is less attractive to an aphid parasitoid, in terms of both olfactory preference behaviour and oviposition, than the volatile blend from aphid-infested plants without rhizobacteria. Importantly, the effect of rhizobacteria on both the emission of herbivore-induced volatiles and parasitoid response to aphid-infested plants is lost in an Arabidopsis mutant (aos/dde2-2) that is impaired in jasmonic acid production. By modifying the blend of herbivore-induced plant volatiles that depend on the jasmonic acid-signalling pathway, root-colonizing microbes interfere with the attraction of parasitoids of leaf herbivores. © 2012 Blackwell Publishing Ltd.
Jasmonate-Mediated Induced Volatiles in the American Cranberry, Vaccinium macrocarpon: From Gene Expression to Organismal Interactions

PubMed Central

Rodriguez-Saona, Cesar R.; Polashock, James; Malo, Edi A.

2013-01-01

Jasmonates, i.e., jasmonic acid (JA) and methyl jasmonate (MeJA), are signaling hormones that regulate a large number of defense responses in plants which in turn affect the plants’ interactions with herbivores and their natural enemies. Here, we investigated the effect of jasmonates on the emission of volatiles in the American cranberry, Vaccinium macrocarpon, at different levels of biological organization from gene expression to organismal interactions. At the molecular level, four genes (BCS, LLS, NER1, and TPS21) responded significantly to gypsy moth larval feeding, MeJA, and mechanical wounding, but to different degrees. The most dramatic changes in expression of BCS and TPS21 (genes in the sesquiterpenoid pathway) were when treated with MeJA. Gypsy moth-damaged and MeJA-treated plants also had significantly elevated expression of LLS and NER1 (genes in the monoterpene and homoterpene biosynthesis pathways, respectively). At the biochemical level, MeJA induced a complex blend of monoterpene and sesquiterpene compounds that differed from gypsy moth and mechanical damage, and followed a diurnal pattern of emission. At the organismal level, numbers of Sparganothis sulfureana moths were lower while numbers of parasitic wasps were higher on sticky traps near MeJA-treated cranberry plants than those near untreated plants. Out of 11 leaf volatiles tested, (Z)-3-hexenyl acetate, linalool, and linalool oxide elicited strong antennal (EAG) responses from S. sulfureana, whereas sesquiterpenes elicited weak EAG responses. In addition, mortality of S. sulfureana larvae increased by about 43% in JA treated cranberry plants as compared with untreated plants, indicating a relationship among adult preference, antennal sensitivity to plant odors, and offspring performance. This study highlights the role of the jasmonate-dependent defensive pathway in the emissions of herbivore-induced volatiles in cranberries and its importance in multi-trophic level interactions. PMID

Jasmonate-Mediated Induced Volatiles in the American Cranberry, Vaccinium macrocarpon: From Gene Expression to Organismal Interactions.

PubMed

Rodriguez-Saona, Cesar R; Polashock, James; Malo, Edi A

2013-01-01

Jasmonates, i.e., jasmonic acid (JA) and methyl jasmonate (MeJA), are signaling hormones that regulate a large number of defense responses in plants which in turn affect the plants' interactions with herbivores and their natural enemies. Here, we investigated the effect of jasmonates on the emission of volatiles in the American cranberry, Vaccinium macrocarpon, at different levels of biological organization from gene expression to organismal interactions. At the molecular level, four genes (BCS, LLS, NER1, and TPS21) responded significantly to gypsy moth larval feeding, MeJA, and mechanical wounding, but to different degrees. The most dramatic changes in expression of BCS and TPS21 (genes in the sesquiterpenoid pathway) were when treated with MeJA. Gypsy moth-damaged and MeJA-treated plants also had significantly elevated expression of LLS and NER1 (genes in the monoterpene and homoterpene biosynthesis pathways, respectively). At the biochemical level, MeJA induced a complex blend of monoterpene and sesquiterpene compounds that differed from gypsy moth and mechanical damage, and followed a diurnal pattern of emission. At the organismal level, numbers of Sparganothis sulfureana moths were lower while numbers of parasitic wasps were higher on sticky traps near MeJA-treated cranberry plants than those near untreated plants. Out of 11 leaf volatiles tested, (Z)-3-hexenyl acetate, linalool, and linalool oxide elicited strong antennal (EAG) responses from S. sulfureana, whereas sesquiterpenes elicited weak EAG responses. In addition, mortality of S. sulfureana larvae increased by about 43% in JA treated cranberry plants as compared with untreated plants, indicating a relationship among adult preference, antennal sensitivity to plant odors, and offspring performance. This study highlights the role of the jasmonate-dependent defensive pathway in the emissions of herbivore-induced volatiles in cranberries and its importance in multi-trophic level interactions.
AtWRKY22 promotes susceptibility to aphids and modulates salicylic acid and jasmonic acid signalling

PubMed Central

Kloth, Karen J.; Wiegers, Gerrie L.; Busscher-Lange, Jacqueline; van Haarst, Jan C.; Kruijer, Willem; Bouwmeester, Harro J.; Dicke, Marcel; Jongsma, Maarten A.

2016-01-01

Aphids induce many transcriptional perturbations in their host plants, but the signalling cascades responsible and the effects on plant resistance are largely unknown. Through a genome-wide association (GWA) mapping study in Arabidopsis thaliana, we identified WRKY22 as a candidate gene associated with feeding behaviour of the green peach aphid, Myzus persicae. The transcription factor WRKY22 is known to be involved in pathogen-triggered immunity, and WRKY22 gene expression has been shown to be induced by aphids. Assessment of aphid population development and feeding behaviour on knockout mutants and overexpression lines showed that WRKY22 increases susceptibility to M. persicae via a mesophyll-located mechanism. mRNA sequencing analysis of aphid-infested wrky22 knockout plants revealed the up-regulation of genes involved in salicylic acid (SA) signalling and down-regulation of genes involved in plant growth and cell-wall loosening. In addition, mechanostimulation of knockout plants by clip cages up-regulated jasmonic acid (JA)-responsive genes, resulting in substantial negative JA–SA crosstalk. Based on this and previous studies, WRKY22 is considered to modulate the interplay between the SA and JA pathways in response to a wide range of biotic and abiotic stimuli. Its induction by aphids and its role in suppressing SA and JA signalling make WRKY22 a potential target for aphids to manipulate host plant defences. PMID:27107291
Bioassays for assessing jasmonate-dependent defenses triggered by pathogens, herbivorous insects, or beneficial rhizobacteria.

PubMed

Van Wees, Saskia C M; Van Pelt, Johan A; Bakker, Peter A H M; Pieterse, Corné M J

2013-01-01

Jasmonates, together with other plant hormones, are important orchestrators of the plant immune system. The different hormone-controlled signaling pathways cross-communicate in an antagonistic or a synergistic manner, providing the plant with a powerful capacity to finely regulate its immune response. Jasmonic acid (JA) signaling is required for plant resistance to harmful organisms, such as necrotrophic pathogens and herbivorous insects. Furthermore, JA signaling is essential in interactions of plants with beneficial microbes that induce systemic resistance to pathogens and insects. The role of JA signaling components in plant immunity can be studied by performing bioassays with different interacting organisms. Determination of the level of resistance and the induction of defense responses in plants with altered JA components, through mutation or ectopic expression, will unveil novel mechanisms of JA signaling. We provide detailed protocols of bioassays with the model plant Arabidopsis thaliana challenged with the pathogens Botrytis cinerea and Pseudomonas syringae, the insect herbivore Pieris rapae, and the beneficial microbe Pseudomonas fluorescens. In addition, we describe pharmacological assays to study the modulation of JA-regulated responses by exogenous application of combinations of hormones, because a simultaneous rise in hormone levels occurs during interaction of plants with other organisms.
Jasmonic acid and salicylic acid activate a common defense system in rice.

PubMed

Tamaoki, Daisuke; Seo, Shigemi; Yamada, Shoko; Kano, Akihito; Miyamoto, Ayumi; Shishido, Hodaka; Miyoshi, Seika; Taniguchi, Shiduku; Akimitsu, Kazuya; Gomi, Kenji

2013-06-01

Jasmonic acid (JA) and salicylic acid (SA) play important roles in plant defense systems. JA and SA signaling pathways interact antagonistically in dicotyledonous plants, but, the status of crosstalk between JA and SA signaling is unknown in monocots. Our rice microarray analysis showed that more than half of the genes upregulated by the SA analog BTH are also upregulated by JA, suggesting that a major portion of the SA-upregulated genes are regulated by JA-dependent signaling in rice. A common defense system that is activated by both JA and SA is thus proposed which plays an important role in pathogen defense responses in rice.
Insights into the origin and evolution of the plant hormone signaling machinery.

PubMed

Wang, Chunyang; Liu, Yang; Li, Si-Shen; Han, Guan-Zhu

2015-03-01

Plant hormones modulate plant growth, development, and defense. However, many aspects of the origin and evolution of plant hormone signaling pathways remain obscure. Here, we use a comparative genomic and phylogenetic approach to investigate the origin and evolution of nine major plant hormone (abscisic acid, auxin, brassinosteroid, cytokinin, ethylene, gibberellin, jasmonate, salicylic acid, and strigolactone) signaling pathways. Our multispecies genome-wide analysis reveals that: (1) auxin, cytokinin, and strigolactone signaling pathways originated in charophyte lineages; (2) abscisic acid, jasmonate, and salicylic acid signaling pathways arose in the last common ancestor of land plants; (3) gibberellin signaling evolved after the divergence of bryophytes from land plants; (4) the canonical brassinosteroid signaling originated before the emergence of angiosperms but likely after the split of gymnosperms and angiosperms; and (5) the origin of the canonical ethylene signaling pathway postdates shortly the emergence of angiosperms. Our findings might have important implications in understanding the molecular mechanisms underlying the emergence of land plants. © 2015 American Society of Plant Biologists. All Rights Reserved.
Differential expression of jasmonate biosynthesis genes in cacao genotypes contrasting for resistance against Moniliophthora perniciosa.

PubMed

Litholdo, Celso G; Leal, Gildemberg A; Albuquerque, Paulo S B; Figueira, Antonio

2015-10-01

The resistance mechanism of cacao against M. perniciosa is likely to be mediated by JA/ET-signaling pathways due to the preferential TcAOS and TcSAM induction in a resistant genotype. The basidiomycete Moniliophthora perniciosa causes a serious disease in cacao (Theobroma cacao L.), and the use of resistant varieties is the only sustainable long-term solution. Cacao resistance against M. perniciosa is characterized by pathogen growth inhibition with reduced colonization and an attenuation of disease symptoms, suggesting a regulation by jasmonate (JA)/ethylene (ET) signaling pathways. The hypothesis that genes involved in JA biosynthesis would be active in the interaction of T. cacao and M. perniciosa was tested here. The cacao JA-related genes were evaluated for their relative quantitative expression in susceptible and resistant genotypes upon the exogenous application of ET, methyl-jasmonate (MJ), and salicylic acid (SA), or after M. perniciosa inoculation. MJ treatment triggered changes in the expression of genes involved in JA biosynthesis, indicating that the mechanism of positive regulation by exogenous MJ application occurs in cacao. However, a higher induction of these genes was observed in the susceptible genotype. Further, a contrast in JA-related transcriptional expression was detected between susceptible and resistant plants under M. perniciosa infection, with the induction of the allene oxide synthase gene (TcAOS), which encodes a key enzyme in the JA biosynthesis pathway in the resistant genotype. Altogether, this work provides additional evidences that the JA-dependent signaling pathway is modulating the defense response against M. perniciosa in a cacao-resistant genotype.
OsMYC2 mediates numerous defence-related transcriptional changes via jasmonic acid signalling in rice.

PubMed

Ogawa, Satoshi; Kawahara-Miki, Ryouka; Miyamoto, Koji; Yamane, Hisakazu; Nojiri, Hideaki; Tsujii, Yoshimasa; Okada, Kazunori

2017-05-06

Jasmonic acid (JA) plays central roles in various events in plants, especially defence against pathogens and insects. The basic helix-loop-helix (bHLH) transcription factor MYC2 has attracted attention as a master regulator of JA signalling in dicotyledonous plants. However, how MYC2 functions in monocotyledonous plants, including agriculturally important crops such as cultivated rice, has been poorly understood. To elucidate the comprehensive effects of rice MYC2 (OsMYC2) on the JA-inducible transcriptional modifications, we performed RNA-sequencing by using OsMYC2-knockdown plants (osmyc2RNAi). In osmyc2RNAi, JA-inducible expression of many defence-related genes, for example chitinases and proteinase inhibitors, was compromised. Decrease in JA-dependent activation of the biosynthetic pathways of specialised metabolites, especially defence compounds, was also evident in the osmyc2RNAi line. Furthermore, a substantial change was noted in the expression of distinct types of transcription factors, such as MYB-type factors, likely depicting the importance of OsMYC2 in not only defence responses but also other morphogenetic events. Our findings provide fundamental information to understand the overall functions of MYC2 in JA signalling in monocotyledonous plants, which might yield agricultural benefits. Copyright © 2017 Elsevier Inc. All rights reserved.
Jasmonate signaling in plant stress responses and development - active and inactive compounds.

PubMed

Wasternack, Claus; Strnad, Miroslav

2016-09-25

Jasmonates (JAs) are lipid-derived signals mediating plant responses to biotic and abiotic stresses and in plant development. Following the elucidation of each step in their biosynthesis and the important components of perception and signaling, several activators, repressors and co-repressors have been identified which contribute to fine-tuning the regulation of JA-induced gene expression. Many of the metabolic reactions in which JA participates, such as conjugation with amino acids, glucosylation, hydroxylation, carboxylation, sulfation and methylation, lead to numerous compounds with different biological activities. These metabolites may be highly active, partially active in specific processes or inactive. Hydroxylation, carboxylation and sulfation inactivate JA signaling. The precursor of JA biosynthesis, 12-oxo-phytodienoic acid (OPDA), has been identified as a JA-independent signaling compound. An increasing number of OPDA-specific processes is being identified. To conclude, the numerous JA compounds and their different modes of action allow plants to respond specifically and flexibly to alterations in the environment. Copyright © 2015 Elsevier B.V. All rights reserved.
Flower-specific jasmonate signaling regulates constitutive floral defenses in wild tobacco

PubMed Central

Li, Ran; Wang, Ming; Wang, Yang; Schuman, Meredith C.; Weinhold, Arne; Schäfer, Martin; Jiménez-Alemán, Guillermo H.; Barthel, Andrea; Baldwin, Ian T.

2017-01-01

Optimal defense (OD) theory predicts that within a plant, tissues are defended in proportion to their fitness value and risk of predation. The fitness value of leaves varies greatly and leaves are protected by jasmonate (JA)-inducible defenses. Flowers are vehicles of Darwinian fitness in flowering plants and are attacked by herbivores and pathogens, but how they are defended is rarely investigated. We used Nicotiana attenuata, an ecological model plant with well-characterized herbivore interactions to characterize defense responses in flowers. Early floral stages constitutively accumulate greater amounts of two well-characterized defensive compounds, the volatile (E)-α-bergamotene and trypsin proteinase inhibitors (TPIs), which are also found in herbivore-induced leaves. Plants rendered deficient in JA biosynthesis or perception by RNA interference had significantly attenuated floral accumulations of defensive compounds known to be regulated by JA in leaves. By RNA-seq, we found a JAZ gene, NaJAZi, specifically expressed in early-stage floral tissues. Gene silencing revealed that NaJAZi functions as a flower-specific jasmonate repressor that regulates JAs, (E)-α-bergamotene, TPIs, and a defensin. Flowers silenced in NaJAZi are more resistant to tobacco budworm attack, a florivore. When the defensin was ectopically expressed in leaves, performance of Manduca sexta larvae, a folivore, decreased. NaJAZi physically interacts with a newly identified NINJA-like protein, but not the canonical NINJA. This NINJA-like recruits the corepressor TOPLESS that contributes to the suppressive function of NaJAZi on floral defenses. This study uncovers the defensive function of JA signaling in flowers, which includes components that tailor JA signaling to provide flower-specific defense. PMID:28784761
Chitosan oligosaccharide induces resistance to Tobacco mosaic virus in Arabidopsis via the salicylic acid-mediated signalling pathway

PubMed Central

Jia, Xiaochen; Meng, Qingshan; Zeng, Haihong; Wang, Wenxia; Yin, Heng

2016-01-01

Chitosan is one of the most abundant carbohydrate biopolymers in the world, and chitosan oligosaccharide (COS), which is prepared from chitosan, is a plant immunity regulator. The present study aimed to validate the effect of COS on inducing resistance to tobacco mosaic virus (TMV) in Arabidopsis and to investigate the potential defence-related signalling pathways involved. Optimal conditions for the induction of TMV resistance in Arabidopsis were COS pretreatment at 50 mg/L for 1 day prior to inoculation with TMV. Multilevel indices, including phenotype data, and TMV coat protein expression, revealed that COS induced TMV resistance in wild-type and jasmonic acid pathway- deficient (jar1) Arabidopsis plants, but not in salicylic acid pathway deficient (NahG) Arabidopsis plants. Quantitative-PCR and analysis of phytohormone levels confirmed that COS pretreatment enhanced the expression of the defence-related gene PR1, which is a marker of salicylic acid signalling pathway, and increased the amount of salicylic acid in WT and jar1, but not in NahG plants. Taken together, these results confirm that COS induces TMV resistance in Arabidopsis via activation of the salicylic acid signalling pathway. PMID:27189192
Chitosan oligosaccharide induces resistance to Tobacco mosaic virus in Arabidopsis via the salicylic acid-mediated signalling pathway.

PubMed

Jia, Xiaochen; Meng, Qingshan; Zeng, Haihong; Wang, Wenxia; Yin, Heng

2016-05-18

Chitosan is one of the most abundant carbohydrate biopolymers in the world, and chitosan oligosaccharide (COS), which is prepared from chitosan, is a plant immunity regulator. The present study aimed to validate the effect of COS on inducing resistance to tobacco mosaic virus (TMV) in Arabidopsis and to investigate the potential defence-related signalling pathways involved. Optimal conditions for the induction of TMV resistance in Arabidopsis were COS pretreatment at 50 mg/L for 1 day prior to inoculation with TMV. Multilevel indices, including phenotype data, and TMV coat protein expression, revealed that COS induced TMV resistance in wild-type and jasmonic acid pathway- deficient (jar1) Arabidopsis plants, but not in salicylic acid pathway deficient (NahG) Arabidopsis plants. Quantitative-PCR and analysis of phytohormone levels confirmed that COS pretreatment enhanced the expression of the defence-related gene PR1, which is a marker of salicylic acid signalling pathway, and increased the amount of salicylic acid in WT and jar1, but not in NahG plants. Taken together, these results confirm that COS induces TMV resistance in Arabidopsis via activation of the salicylic acid signalling pathway.
Weights in the balance: jasmonic acid and salicylic acid signaling in root-biotroph interactions.

PubMed

Gutjahr, Caroline; Paszkowski, Uta

2009-07-01

Work on the interaction of aerial plant parts with pathogens has identified the signaling molecules jasmonic acid (JA) and salicylic acid (SA) as important players in induced defense of the plant against invading organisms. Much less is known about the role of JA and SA signaling in root infection. Recent progress has been made in research on plant interactions with biotrophic mutualists and parasites that exclusively associate with roots, namely arbuscular mycorrhizal and rhizobial symbioses on one hand and nematode and parasitic plant interactions on the other hand. Here, we review these recent advances relating JA and SA signaling to specific stages of root colonization and discuss how both signaling molecules contribute to a balance between compatibility and defense in mutualistic as well as parasitic biotroph-root interactions.
Both the Jasmonic Acid and the Salicylic Acid Pathways Contribute to Resistance to the Biotrophic Clubroot Agent Plasmodiophora brassicae in Arabidopsis.

PubMed

Lemarié, Séverine; Robert-Seilaniantz, Alexandre; Lariagon, Christine; Lemoine, Jocelyne; Marnet, Nathalie; Jubault, Mélanie; Manzanares-Dauleux, Maria J; Gravot, Antoine

2015-11-01

The role of salicylic acid (SA) and jasmonic acid (JA) signaling in resistance to root pathogens has been poorly documented. We assessed the contribution of SA and JA to basal and partial resistance of Arabidopsis to the biotrophic clubroot agent Plasmodiophora brassicae. SA and JA levels as well as the expression of the SA-responsive genes PR2 and PR5 and the JA-responsive genes ARGAH2 and THI2.1 were monitored in infected roots of the accessions Col-0 (susceptible) and Bur-0 (partially resistant). SA signaling was activated in Bur-0 but not in Col-0. The JA pathway was weakly activated in Bur-0 but was strongly induced in Col-0. The contribution of both pathways to clubroot resistance was then assessed using exogenous phytohormone application and mutants affected in SA or JA signaling. Exogenous SA treatment decreased clubroot symptoms in the two Arabidopsis accessions, whereas JA treatment reduced clubroot symptoms only in Col-0. The cpr5-2 mutant, in which SA responses are constitutively induced, was more resistant to clubroot than the corresponding wild type, and the JA signaling-deficient mutant jar1 was more susceptible. Finally, we showed that the JA-mediated induction of NATA1 drove N(δ)-acetylornithine biosynthesis in infected Col-0 roots. The 35S::NATA1 and nata1 lines displayed reduced or enhanced clubroot symptoms, respectively, thus suggesting that in Col-0 this pathway was involved in the JA-mediated basal clubroot resistance. Overall, our data support the idea that, depending on the Arabidopsis accession, both SA and JA signaling can play a role in partial inhibition of clubroot development in compatible interactions with P. brassicae. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.
A fungal endophyte helps plants to tolerate root herbivory through changes in gibberellin and jasmonate signaling.

PubMed

Cosme, Marco; Lu, Jing; Erb, Matthias; Stout, Michael Joseph; Franken, Philipp; Wurst, Susanne

2016-08-01

Plant-microbe mutualisms can improve plant defense, but the impact of root endophytes on below-ground herbivore interactions remains unknown. We investigated the effects of the root endophyte Piriformospora indica on interactions between rice (Oryza sativa) plants and its root herbivore rice water weevil (RWW; Lissorhoptrus oryzophilus), and how plant jasmonic acid (JA) and GA regulate this tripartite interaction. Glasshouse experiments with wild-type rice and coi1-18 and Eui1-OX mutants combined with nutrient, jasmonate and gene expression analyses were used to test: whether RWW adult herbivory above ground influences subsequent damage caused by larval herbivory below ground; whether P. indica protects plants against RWW; and whether GA and JA signaling mediate these interactions. The endophyte induced plant tolerance to root herbivory. RWW adults and larvae acted synergistically via JA signaling to reduce root growth, while endophyte-elicited GA biosynthesis suppressed the herbivore-induced JA in roots and recovered plant growth. Our study shows for the first time the impact of a root endophyte on plant defense against below-ground herbivores, adds to growing evidence that induced tolerance may be an important root defense, and implicates GA as a signal component of inducible plant tolerance against biotic stress. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.
AtWRKY22 promotes susceptibility to aphids and modulates salicylic acid and jasmonic acid signalling.

PubMed

Kloth, Karen J; Wiegers, Gerrie L; Busscher-Lange, Jacqueline; van Haarst, Jan C; Kruijer, Willem; Bouwmeester, Harro J; Dicke, Marcel; Jongsma, Maarten A

2016-05-01

Aphids induce many transcriptional perturbations in their host plants, but the signalling cascades responsible and the effects on plant resistance are largely unknown. Through a genome-wide association (GWA) mapping study in Arabidopsis thaliana, we identified WRKY22 as a candidate gene associated with feeding behaviour of the green peach aphid, Myzus persicae The transcription factor WRKY22 is known to be involved in pathogen-triggered immunity, and WRKY22 gene expression has been shown to be induced by aphids. Assessment of aphid population development and feeding behaviour on knockout mutants and overexpression lines showed that WRKY22 increases susceptibility to M. persicae via a mesophyll-located mechanism. mRNA sequencing analysis of aphid-infested wrky22 knockout plants revealed the up-regulation of genes involved in salicylic acid (SA) signalling and down-regulation of genes involved in plant growth and cell-wall loosening. In addition, mechanostimulation of knockout plants by clip cages up-regulated jasmonic acid (JA)-responsive genes, resulting in substantial negative JA-SA crosstalk. Based on this and previous studies, WRKY22 is considered to modulate the interplay between the SA and JA pathways in response to a wide range of biotic and abiotic stimuli. Its induction by aphids and its role in suppressing SA and JA signalling make WRKY22 a potential target for aphids to manipulate host plant defences. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.
Identification and Analysis of Jasmonate Pathway Genes in Coffea canephora (Robusta Coffee) by In Silico Approach.

PubMed

Bharathi, Kosaraju; Sreenath, H L

2017-07-01

Coffea canephora is the commonly cultivated coffee species in the world along with Coffea arabica . Different pests and pathogens affect the production and quality of the coffee. Jasmonic acid (JA) is a plant hormone which plays an important role in plants growth, development, and defense mechanisms, particularly against insect pests. The key enzymes involved in the production of JA are lipoxygenase, allene oxide synthase, allene oxide cyclase, and 12-oxo-phytodienoic reductase. There is no report on the genes involved in JA pathway in coffee plants. We made an attempt to identify and analyze the genes coding for these enzymes in C. canephora . First, protein sequences of jasmonate pathway genes from model plant Arabidopsis thaliana were identified in the National Center for Biotechnology Information (NCBI) database. These protein sequences were used to search the web-based database Coffee Genome Hub to identify homologous protein sequences in C. canephora genome using Basic Local Alignment Search Tool (BLAST). Homologous protein sequences for key genes were identified in the C. canephora genome database. Protein sequences of the top matches were in turn used to search in NCBI database using BLAST tool to confirm the identity of the selected proteins and to identify closely related genes in species. The protein sequences from C. canephora database and the top matches in NCBI were aligned, and phylogenetic trees were constructed using MEGA6 software and identified the genetic distance of the respective genes. The study identified the four key genes of JA pathway in C. canephora , confirming the conserved nature of the pathway in coffee. The study expected to be useful to further explore the defense mechanisms of coffee plants. JA is a plant hormone that plays an important role in plant defense against insect pests. Genes coding for the 4 key enzymes involved in the production of JA viz., LOX, AOS, AOC, and OPR are identified in C. canephora (robusta coffee) by
Benefits of jasmonate-dependent defenses against vertebrate herbivores in nature.

PubMed

Machado, Ricardo Ar; McClure, Mark; Hervé, Maxime R; Baldwin, Ian T; Erb, Matthias

2016-06-29

Endogenous jasmonates are important regulators of plant defenses. If and how they enable plants to maintain their reproductive output when facing community-level herbivory under natural conditions, however, remains unknown. We demonstrate that jasmonate-deficient Nicotiana attenuata plants suffer more damage by arthropod and vertebrate herbivores than jasmonate-producing plants in nature. However, only damage by vertebrate herbivores translates into a significant reduction in flower production. Vertebrate stem peeling has the strongest negative impact on plant flower production. Stems are defended by jasmonate-dependent nicotine, and the native cottontail rabbit Sylvilagus nuttallii avoids jasmonate-producing N. attenuata shoots because of their high levels of nicotine. Thus, endogenous jasmonates enable plants to resist different types of herbivores in nature, and jasmonate-dependent defenses are important for plants to maintain their reproductive potential when facing vertebrate herbivory. Ecological and evolutionary models on plant defense signaling should aim at integrating arthropod and vertebrate herbivory at the community level.
Jasmonate perception by inositol-phosphate-potentiated COI1-JAZ co-receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheard, Laura B; Tan, Xu; Mao, Haibin

2011-11-07

Jasmonates are a family of plant hormones that regulate plant growth, development and responses to stress. The F-box protein CORONATINE INSENSITIVE 1 (COI1) mediates jasmonate signalling by promoting hormone-dependent ubiquitylation and degradation of transcriptional repressor JAZ proteins. Despite its importance, the mechanism of jasmonate perception remains unclear. Here we present structural and pharmacological data to show that the true Arabidopsis jasmonate receptor is a complex of both COI1 and JAZ. COI1 contains an open pocket that recognizes the bioactive hormone (3R,7S)-jasmonoyl-l-isoleucine (JA-Ile) with high specificity. High-affinity hormone binding requires a bipartite JAZ degron sequence consisting of a conserved {alpha}-helix formore » COI1 docking and a loop region to trap the hormone in its binding pocket. In addition, we identify a third critical component of the jasmonate co-receptor complex, inositol pentakisphosphate, which interacts with both COI1 and JAZ adjacent to the ligand. Our results unravel the mechanism of jasmonate perception and highlight the ability of F-box proteins to evolve as multi-component signalling hubs.« less
CYP94-mediated jasmonoyl-isoleucine hormone oxidation shapes jasmonate profiles and attenuates defence responses to Botrytis cinerea infection

PubMed Central

Aubert, Yann; Widemann, Emilie; Miesch, Laurence; Pinot, Franck; Heitz, Thierry

2015-01-01

Induced resistance to the necrotrophic pathogen Botrytis cinerea depends on jasmonate metabolism and signalling in Arabidopsis. We have presented here extensive jasmonate profiling in this pathosystem and investigated the impact of the recently reported jasmonoyl-isoleucine (JA-Ile) catabolic pathway mediated by cytochrome P450 (CYP94) enzymes. Using a series of mutant and overexpressing (OE) plant lines, we showed that CYP94B3 and CYP94C1 are integral components of the fungus-induced jasmonate metabolic pathway and control the abundance of oxidized conjugated but also some unconjugated derivatives, such as sulfated 12-HSO4-JA. Despite causing JA-Ile overaccumulation due to impaired oxidation, CYP94 deficiency had negligible impacts on resistance, associated with enhanced JAZ repressor transcript levels. In contrast, plants overexpressing (OE) CYP94B3 or CYP94C1 were enriched in 12-OH-JA-Ile or 12-COOH-JA-Ile respectively. This shift towards oxidized JA-Ile derivatives was concomitant with strongly impaired defence gene induction and reduced disease resistance. CYP94B3-OE, but unexpectedly not CYP94C1-OE, plants displayed reduced JA-Ile levels compared with the wild type, suggesting that increased susceptibility in CYP94C1-OE plants may result from changes in the hormone oxidation ratio rather than absolute changes in JA-Ile levels. Consistently, while feeding JA-Ile to seedlings triggered strong induction of JA pathway genes, induction was largely reduced or abolished after feeding with the CYP94 products 12-OH-JA-Ile and 12-COOH-JA-Ile, respectively. This trend paralleled in vitro pull-down assays where 12-COOH-JA-Ile was unable to promote COI1–JAZ9 co-receptor assembly. Our results highlight the dual function of CYP94B3/C1 in antimicrobial defence: by controlling hormone oxidation status for signal attenuation, these enzymes also define JA-Ile as a metabolic hub directing jasmonate profile complexity. PMID:25903915
The plastidial retrograde signal methyl erythritol cyclopyrophosphate is a regulator of salicylic acid and jasmonic acid crosstalk

PubMed Central

Lemos, Mark; Xiao, Yanmei; Bjornson, Marta; Wang, Jin-zheng; Hicks, Derrick; de Souza, Amancio; Wang, Chang-Quan; Yang, Panyu; Ma, Shisong; Dinesh-Kumar, Savithramma; Dehesh, Katayoon

2016-01-01

The exquisite harmony between hormones and their corresponding signaling pathways is central to prioritizing plant responses to simultaneous and/or successive environmental trepidations. The crosstalk between jasmonic acid (JA) and salicylic acid (SA) is an established effective mechanism that optimizes and tailors plant adaptive responses. However, the underlying regulatory modules of this crosstalk are largely unknown. Global transcriptomic analyses of mutant plants (ceh1) with elevated levels of the stress-induced plastidial retrograde signaling metabolite 2-C-methyl-D-erythritol cyclopyrophosphate (MEcPP) revealed robustly induced JA marker genes, expected to be suppressed by the presence of constitutively high SA levels in the mutant background. Analyses of a range of genotypes with varying SA and MEcPP levels established the selective role of MEcPP-mediated signal(s) in induction of JA-responsive genes in the presence of elevated SA. Metabolic profiling revealed the presence of high levels of the JA precursor 12-oxo-phytodienoic acid (OPDA), but near wild type levels of JA in the ceh1 mutant plants. Analyses of coronatine-insensitive 1 (coi1)/ceh1 double mutant plants confirmed that the MEcPP-mediated induction is JA receptor COI1 dependent, potentially through elevated OPDA. These findings identify MEcPP as a previously unrecognized central regulatory module that induces JA-responsive genes in the presence of high SA, thereby staging a multifaceted plant response within the environmental context. PMID:26733689

Benefits of jasmonate-dependent defenses against vertebrate herbivores in nature

PubMed Central

Machado, Ricardo AR; McClure, Mark; Hervé, Maxime R; Baldwin, Ian T; Erb, Matthias

2016-01-01

Endogenous jasmonates are important regulators of plant defenses. If and how they enable plants to maintain their reproductive output when facing community-level herbivory under natural conditions, however, remains unknown. We demonstrate that jasmonate-deficient Nicotiana attenuata plants suffer more damage by arthropod and vertebrate herbivores than jasmonate-producing plants in nature. However, only damage by vertebrate herbivores translates into a significant reduction in flower production. Vertebrate stem peeling has the strongest negative impact on plant flower production. Stems are defended by jasmonate-dependent nicotine, and the native cottontail rabbit Sylvilagus nuttallii avoids jasmonate-producing N. attenuata shoots because of their high levels of nicotine. Thus, endogenous jasmonates enable plants to resist different types of herbivores in nature, and jasmonate-dependent defenses are important for plants to maintain their reproductive potential when facing vertebrate herbivory. Ecological and evolutionary models on plant defense signaling should aim at integrating arthropod and vertebrate herbivory at the community level. DOI: http://dx.doi.org/10.7554/eLife.13720.001 PMID:27352734
SlMAPK3 enhances tolerance to tomato yellow leaf curl virus (TYLCV) by regulating salicylic acid and jasmonic acid signaling in tomato (Solanum lycopersicum)

PubMed Central

Li, Yunzhou; Qin, Lei; Zhao, Jingjing; Muhammad, Tayeb; Cao, Hehe; Li, Hailiang; Zhang, Yan; Liang, Yan

2017-01-01

Several recent studies have reported on the role of mitogen-activated protein kinase (MAPK3) in plant immune responses. However, little is known about how MAPK3 functions in tomato (Solanum lycopersicum L.) infected with tomato yellow leaf curl virus (TYLCV). There is also uncertainty about the connection between plant MAPK3 and the salicylic acid (SA) and jasmonic acid (JA) defense-signaling pathways. The results of this study indicated that SlMAPK3 participates in the antiviral response against TYLCV. Tomato seedlings were inoculated with TYLCV to investigate the possible roles of SlMAPK1, SlMAPK2, and SlMAPK3 against this virus. Inoculation with TYLCV strongly induced the expression and the activity of all three genes. Silencing of SlMAPK1, SlMAPK2, and SlMAPK3 reduced tolerance to TYLCV, increased leaf H2O2 concentrations, and attenuated expression of defense-related genes after TYLCV infection, especially in SlMAPK3-silenced plants. Exogenous SA and methyl jasmonic acid (MeJA) both significantly induced SlMAPK3 expression in tomato leaves. Over-expression of SlMAPK3 increased the transcript levels of SA/JA-mediated defense-related genes (PR1, PR1b/SlLapA, SlPI-I, and SlPI-II) and enhanced tolerance to TYLCV. After TYLCV inoculation, the leaves of SlMAPK3 over-expressed plants compared with wild type plants showed less H2O2 accumulation and greater superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) activity. Overall, the results suggested that SlMAPK3 participates in the antiviral response of tomato to TYLCV, and that this process may be through either the SA or JA defense-signaling pathways. PMID:28222174
SlMAPK3 enhances tolerance to tomato yellow leaf curl virus (TYLCV) by regulating salicylic acid and jasmonic acid signaling in tomato (Solanum lycopersicum).

PubMed

Li, Yunzhou; Qin, Lei; Zhao, Jingjing; Muhammad, Tayeb; Cao, Hehe; Li, Hailiang; Zhang, Yan; Liang, Yan

2017-01-01

Several recent studies have reported on the role of mitogen-activated protein kinase (MAPK3) in plant immune responses. However, little is known about how MAPK3 functions in tomato (Solanum lycopersicum L.) infected with tomato yellow leaf curl virus (TYLCV). There is also uncertainty about the connection between plant MAPK3 and the salicylic acid (SA) and jasmonic acid (JA) defense-signaling pathways. The results of this study indicated that SlMAPK3 participates in the antiviral response against TYLCV. Tomato seedlings were inoculated with TYLCV to investigate the possible roles of SlMAPK1, SlMAPK2, and SlMAPK3 against this virus. Inoculation with TYLCV strongly induced the expression and the activity of all three genes. Silencing of SlMAPK1, SlMAPK2, and SlMAPK3 reduced tolerance to TYLCV, increased leaf H2O2 concentrations, and attenuated expression of defense-related genes after TYLCV infection, especially in SlMAPK3-silenced plants. Exogenous SA and methyl jasmonic acid (MeJA) both significantly induced SlMAPK3 expression in tomato leaves. Over-expression of SlMAPK3 increased the transcript levels of SA/JA-mediated defense-related genes (PR1, PR1b/SlLapA, SlPI-I, and SlPI-II) and enhanced tolerance to TYLCV. After TYLCV inoculation, the leaves of SlMAPK3 over-expressed plants compared with wild type plants showed less H2O2 accumulation and greater superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) activity. Overall, the results suggested that SlMAPK3 participates in the antiviral response of tomato to TYLCV, and that this process may be through either the SA or JA defense-signaling pathways.
The chromatin remodeler SPLAYED regulates specific stress signaling pathways.

PubMed

Walley, Justin W; Rowe, Heather C; Xiao, Yanmei; Chehab, E Wassim; Kliebenstein, Daniel J; Wagner, Doris; Dehesh, Katayoon

2008-12-01

Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD) is required for the expression of selected genes downstream of the jasmonate (JA) and ethylene (ET) signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks.
Hexanoic acid is a resistance inducer that protects tomato plants against Pseudomonas syringae by priming the jasmonic acid and salicylic acid pathways.

PubMed

Scalschi, Loredana; Vicedo, Begonya; Camañes, Gemma; Fernandez-Crespo, Emma; Lapeña, Leonor; González-Bosch, Carmen; García-Agustín, Pilar

2013-05-01

Hexanoic acid-induced resistance (Hx-IR) is effective against several pathogens in tomato plants. Our study of the mechanisms implicated in Hx-IR against Pseudomonas syringae pv. tomato DC3000 suggests that hexanoic acid (Hx) treatment counteracts the negative effect of coronatine (COR) and jasmonyl-isoleucine (JA-Ile) on the salicylic acid (SA) pathway. In Hx-treated plants, an increase in the expression of jasmonic acid carboxyl methyltransferase (JMT) and the SA marker genes PR1 and PR5 indicates a boost in this signalling pathway at the expense of a decrease in JA-Ile. Moreover, Hx treatment potentiates 12-oxo-phytodienoic acid accumulation, which suggests that this molecule might play a role per se in Hx-IR. These results support a positive relationship between the SA and JA pathways in Hx-primed plants. Furthermore, one of the mechanisms of virulence mediated by COR is stomatal re-opening on infection with P. syringae. In this work, we observed that Hx seems to inhibit stomatal opening in planta in the presence of COR, which suggests that, on infection in tomato, this treatment suppresses effector action to prevent bacterial entry into the mesophyll. © 2012 BSPP AND BLACKWELL PUBLISHING LTD.
Jasmonate is involved in the induction of tyrosine aminotransferase and tocopherol biosynthesis in Arabidopsis thaliana.

PubMed

Sandorf, Iris; Holländer-Czytko, Heike

2002-11-01

Coronatine-inducible tyrosine aminotransferase (TAT), which catalyses the transamination from tyrosine to p-hydroxyphenylpyruvate, is the first enzyme of a pathway leading via homogentisic acid to plastoquinone and tocopherols, the latter of which are known to be radical scavengers in plants. TAT can be also induced by the octadecanoids methyl jasmonate (MeJA) and methyl-12-oxophytodienoic acid (MeOPDA), as well as by wounding, high light, UV light and the herbicide oxyfluorfen. In order to elucidate the role of octadecanoids in the process of TAT induction in Arabidopsis thaliana (L.) Heynh., the jasmonate-deficient mutant delayed dehiscence (dde1) was used, in which the gene for 12-oxophytodienoic acid reductase 3 is disrupted. The amount of immunodetectable TAT was low. The enzyme was still fully induced by coronatine as well as by MeJA although induction by the latter was to a lesser extent and later than in the wild type. Treatment with MeOPDA, wounding and UV light, however, had hardly any effects. Tocopherol levels that showed considerable increases in the wild type after some treatments were much less affected in the mutant. However, starting levels of tocopherol were higher in non-induced dde1 than in the wild type. We conclude that jasmonate plays an important role in the signal transduction pathway regulating TAT activity and the biosynthesis of its product tocopherol.
Methyl jasmonate as a vital substance in plants.

PubMed

Cheong, Jong-Joo; Choi, Yang Do

2003-07-01

The plant floral scent methyl jasmonate (MeJA) has been identified as a vital cellular regulator that mediates diverse developmental processes and defense responses against biotic and abiotic stresses. The pleiotropic effects of MeJA have raised numerous questions about its regulation for biogenesis and mode of action. Characterization of the gene encoding jasmonic acid carboxyl methyltransferase has provided basic information on the role(s) of this phytohormone in gene-activation control and systemic long-distance signaling. Recent approaches using functional genomics and bioinformatics have identified a whole set of MeJA-responsive genes, and provide insights into how plants use volatile signals to withstand diverse and variable environments.
Ethylene and jasmonic acid act as negative modulators during mutualistic symbiosis between Laccaria bicolor and Populus roots.

PubMed

Plett, Jonathan M; Khachane, Amit; Ouassou, Malika; Sundberg, Björn; Kohler, Annegret; Martin, Francis

2014-04-01

The plant hormones ethylene, jasmonic acid and salicylic acid have interconnecting roles during the response of plant tissues to mutualistic and pathogenic symbionts. We used morphological studies of transgenic- or hormone-treated Populus roots as well as whole-genome oligoarrays to examine how these hormones affect root colonization by the mutualistic ectomycorrhizal fungus Laccaria bicolor S238N. We found that genes regulated by ethylene, jasmonic acid and salicylic acid were regulated in the late stages of the interaction between L. bicolor and poplar. Both ethylene and jasmonic acid treatments were found to impede fungal colonization of roots, and this effect was correlated to an increase in the expression of certain transcription factors (e.g. ETHYLENE RESPONSE FACTOR1) and a decrease in the expression of genes associated with microbial perception and cell wall modification. Further, we found that ethylene and jasmonic acid showed extensive transcriptional cross-talk, cross-talk that was opposed by salicylic acid signaling. We conclude that ethylene and jasmonic acid pathways are induced late in the colonization of root tissues in order to limit fungal growth within roots. This induction is probably an adaptive response by the plant such that its growth and vigor are not compromised by the fungus. © 2013 The Authors New Phytologist © 2013 New Phytologist Trust.
Ectopic expression of Arabidopsis genes encoding salicylic acid- and jasmonic acid-related proteins confers partial resistance to soybean cyst nematode (Heterodera glycines) in transgenic soybean roots

USDA-ARS?s Scientific Manuscript database

Background. Extensive studies using the model system Arabidopsis thaliana to elucidate plant defense signaling and pathway networks indicate that salicylic acid (SA) is the key hormone triggering the plant defense response against biotrophic and hemi-biotrophic pathogens, while jasmonic acid (JA) an...
Interacting signal pathways control defense gene expression in Arabidopsis in response to cell wall-degrading enzymes from Erwinia carotovora.

PubMed

Norman-Setterblad, C; Vidal, S; Palva, E T

2000-04-01

We have characterized the role of salicylic acid (SA)-independent defense signaling in Arabidopsis thaliana in response to the plant pathogen Erwinia carotovora subsp. carotovora. Use of pathway-specific target genes as well as signal mutants allowed us to elucidate the role and interactions of ethylene, jasmonic acid (JA), and SA signal pathways in this response. Gene expression studies suggest a central role for both ethylene and JA pathways in the regulation of defense gene expression triggered by the pathogen or by plant cell wall-degrading enzymes (CF) secreted by the pathogen. Our results suggest that ethylene and JA act in concert in this regulation. In addition, CF triggers another, strictly JA-mediated response inhibited by ethylene and SA. SA does not appear to have a major role in activating defense gene expression in response to CF. However, SA may have a dual role in controlling CF-induced gene expression, by enhancing the expression of genes synergistically induced by ethylene and JA and repressing genes induced by JA alone.
Elevated CO2 differentially affects tobacco and rice defense against lepidopteran larvae via the jasmonic acid signaling pathway.

PubMed

Lu, Chengkai; Qi, Jinfeng; Hettenhausen, Christian; Lei, Yunting; Zhang, Jingxiong; Zhang, Mou; Zhang, Cuiping; Song, Juan; Li, Jing; Cao, Guoyan; Malook, Saif Ul; Wu, Jianqiang

2018-05-01

Atmospheric CO 2 levels are rapidly increasing due to human activities. However, the effects of elevated CO 2 (ECO 2 ) on plant defense against insects and the underlying mechanisms remain poorly understood. Here we show that ECO 2 increased the photosynthetic rates and the biomass of tobacco and rice plants, and the chewing lepidopteran insects Spodoptera litura and Mythimna separata gained less and more mass on tobacco and rice plants, respectively. Consistently, under ECO 2 , the levels of jasmonic acid (JA), the main phytohormone controlling plant defense against these lepidopteran insects, as well as the main defense-related metabolites, were increased and decreased in insect-damaged tobacco and rice plants. Importantly, bioassays and quantification of defense-related metabolites in tobacco and rice silenced in JA biosynthesis and perception indicate that ECO 2 changes plant resistance mainly by affecting the JA pathway. We further demonstrate that the defensive metabolites, but not total N or protein, are the main factors contributing to the altered defense levels under ECO 2 . This study illustrates that ECO 2 changes the interplay between plants and insects, and we propose that crops should be studied for their resistance to the major pests under ECO 2 to predict the impact of ECO 2 on future agroecosystems. © 2018 Institute of Botany, Chinese Academy of Sciences.
Delay of iris flower senescence by cytokinins and jasmonates.

PubMed

van Doorn, Wouter G; Çelikel, Fisun G; Pak, Caroline; Harkema, Harmannus

2013-05-01

It is not known whether tepal senescence in Iris flowers is regulated by hormones. We applied hormones and hormone inhibitors to cut flowers and isolated tepals of Iris × hollandica cv. Blue Magic. Treatments with ethylene or ethylene antagonists indicated lack of ethylene involvement. Auxins or auxin inhibitors also did not change the time to senescence. Abscisic acid (ABA) hastened senescence, but an inhibitor of ABA synthesis (norflurazon) had no effect. Gibberellic acid (GA3 ) slightly delayed senescence in some experiments, but in other experiments it was without effect, and gibberellin inhibitors [ancymidol or 4-hydroxy-5-isopropyl-2-methylphenyltrimethyl ammonium chloride-1-piperidine carboxylate (AMO-1618)] were ineffective as well. Salicylic acid (SA) also had no effect. Ethylene, auxins, GA3 and SA affected flower opening, therefore did reach the flower cells. Jasmonates delayed senescence by about 2.0 days. Similarly, cytokinins delayed senescence by about 1.5-2.0 days. Antagonists of the phosphatidylinositol signal transduction pathway (lithium), calcium channels (niguldipine and verapamil), calmodulin action [fluphenazine, trifluoroperazine, phenoxybenzamide and N-(6-aminohexyl)-5-chloro-1-naphtalenesulfonamide hydrochloride (W-7)] or protein kinase activity [1-(5-isoquinolinesulfonyl)-2-methylpiperazine hydrochloride (H-7), N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide hydrochloride (H-8) and N-(2-aminoethyl)-5-isoquinolinesulfonamide dihydrochloride (H-9)] had no effect on senescence, indicating no role of a few common signal transduction pathways relating to hormone effects on senescence. The results indicate that tepal senescence in Iris cv. Blue Magic is not regulated by endogenous ethylene, auxin, gibberellins or SA. A role of ABA can at present not be excluded. The data suggest the hypothesis that cytokinins and jasmonates are among the natural regulators. Copyright © Physiologia Plantarum 2012.
The plastidial retrograde signal methyl erythritol cyclopyrophosphate is a regulator of salicylic acid and jasmonic acid crosstalk.

PubMed

Lemos, Mark; Xiao, Yanmei; Bjornson, Marta; Wang, Jin-Zheng; Hicks, Derrick; Souza, Amancio de; Wang, Chang-Quan; Yang, Panyu; Ma, Shisong; Dinesh-Kumar, Savithramma; Dehesh, Katayoon

2016-03-01

The exquisite harmony between hormones and their corresponding signaling pathways is central to prioritizing plant responses to simultaneous and/or successive environmental trepidations. The crosstalk between jasmonic acid (JA) and salicylic acid (SA) is an established effective mechanism that optimizes and tailors plant adaptive responses. However, the underlying regulatory modules of this crosstalk are largely unknown. Global transcriptomic analyses of mutant plants (ceh1) with elevated levels of the stress-induced plastidial retrograde signaling metabolite 2-C-methyl-D-erythritol cyclopyrophosphate (MEcPP) revealed robustly induced JA marker genes, expected to be suppressed by the presence of constitutively high SA levels in the mutant background. Analyses of a range of genotypes with varying SA and MEcPP levels established the selective role of MEcPP-mediated signal(s) in induction of JA-responsive genes in the presence of elevated SA. Metabolic profiling revealed the presence of high levels of the JA precursor 12-oxo-phytodienoic acid (OPDA), but near wild type levels of JA in the ceh1 mutant plants. Analyses of coronatine-insensitive 1 (coi1)/ceh1 double mutant plants confirmed that the MEcPP-mediated induction is JA receptor COI1 dependent, potentially through elevated OPDA. These findings identify MEcPP as a previously unrecognized central regulatory module that induces JA-responsive genes in the presence of high SA, thereby staging a multifaceted plant response within the environmental context. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.
Physcomitrella patens activates reinforcement of the cell wall, programmed cell death and accumulation of evolutionary conserved defence signals, such as salicylic acid and 12-oxo-phytodienoic acid, but not jasmonic acid, upon Botrytis cinerea infection.

PubMed

Ponce De León, Inés; Schmelz, Eric A; Gaggero, Carina; Castro, Alexandra; Álvarez, Alfonso; Montesano, Marcos

2012-10-01

The moss Physcomitrella patens is an evolutionarily basal model system suitable for the analysis of plant defence responses activated after pathogen assault. Upon infection with the necrotroph Botrytis cinerea, several defence mechanisms are induced in P. patens, including the fortification of the plant cell wall by the incorporation of phenolic compounds and the induced expression of related genes. Botrytis cinerea infection also activates the accumulation of reactive oxygen species and cell death with hallmarks of programmed cell death in moss tissues. Salicylic acid (SA) levels also increase after fungal infection, and treatment with SA enhances transcript accumulation of the defence gene phenylalanine ammonia-lyase (PAL) in P. patens colonies. The expression levels of the genes involved in 12-oxo-phytodienoic acid (OPDA) synthesis, including lipoxygenase (LOX) and allene oxide synthase (AOS), increase in P. patens gametophytes after pathogen assault, together with a rise in free linolenic acid and OPDA concentrations. However, jasmonic acid (JA) could not be detected in healthy or infected tissues of this plant. Our results suggest that, although conserved defence signals, such as SA and OPDA, are synthesized and are probably involved in the defence response of P. patens against B. cinerea infection, JA production appears to be missing. Interestingly, P. patens responds to OPDA and methyl jasmonate by reducing moss colony growth and rhizoid length, suggesting that jasmonate perception is present in mosses. Thus, P. patens can provide clues with regard to the evolution of different defence pathways in plants, including signalling and perception of OPDA and jasmonates in nonflowering and flowering plants. © 2012 THE AUTHORS. MOLECULAR PLANT PATHOLOGY © 2012 BSPP AND BLACKWELL PUBLISHING LTD.
The Chromatin Remodeler SPLAYED Regulates Specific Stress Signaling Pathways

PubMed Central

Walley, Justin W.; Rowe, Heather C.; Xiao, Yanmei; Chehab, E. Wassim; Kliebenstein, Daniel J.; Wagner, Doris; Dehesh, Katayoon

2008-01-01

Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD) is required for the expression of selected genes downstream of the jasmonate (JA) and ethylene (ET) signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks. PMID:19079584
Friends or foes: new insights in jasmonate and ethylene co-actions.

PubMed

Zhu, Ziqiang; Lee, Benjamin

2015-03-01

One strategy for sessile plants to adapt to their surrounding environment involves the modulation of their various internal phytohormone signaling and distributions when the plants sense environmental change. There are currently dozens of identified phytohormones in plant cells and they act in concert to regulate plant growth, development, metabolism and defense. It has been determined that phytohormones often act together to achieve certain physiological functions. Thus, the study of hormone-hormone interactions is becoming a competitive research field for deciphering the underlying regulatory mechanisms. Among phytohormones, jasmonate and ethylene present a fascinating case of synergism and antagonism. They are commonly recognized as defense hormones that act synergistically. Plants impaired in jasmonate and/or ethylene signaling are susceptible to infections by necrotrophic fungi, suggesting that these two hormones are both required for defense. Moreover, jasmonate and ethylene also act antagonistically, such as in the regulation of apical hook development and wounding responses. Here, we highlight the recent breakthroughs in the understanding of jasmonate-ethylene co-actions and point out the potential power of studying protein-protein interactions for systematically exploring signal cross-talk. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.
TIME FOR COFFEE Represses Accumulation of the MYC2 Transcription Factor to Provide Time-of-Day Regulation of Jasmonate Signaling in Arabidopsis[C][W][OA

PubMed Central

Shin, Jieun; Heidrich, Katharina; Sanchez-Villarreal, Alfredo; Parker, Jane E.; Davis, Seth J.

2012-01-01

Plants are confronted with predictable daily biotic and abiotic stresses that result from the day–night cycle. The circadian clock provides an anticipation mechanism to respond to these daily stress signals to increase fitness. Jasmonate (JA) is a phytohormone that mediates various growth and stress responses. Here, we found that the circadian-clock component TIME FOR COFFEE (TIC) acts as a negative factor in the JA-signaling pathway. We showed that the tic mutant is hypersensitive to growth-repressive effects of JA and displays altered JA-regulated gene expression. TIC was found to interact with MYC2, a key transcription factor of JA signaling. From this, we discovered that the circadian clock rhythmically regulates JA signaling. TIC is a key determinant in this circadian-gated process, and as a result, the tic mutant is defective in rhythmic JA responses to pathogen infection. TIC acts here by inhibiting MYC2 protein accumulation and by controlling the transcriptional repression of CORONATINE INSENSITIVE1 in an evening-phase–specific manner. Taken together, we propose that TIC acts as an output component of the circadian oscillator to influence JA signaling directly. PMID:22693280
Behavioural responses of Frankliniella occidentalis Pergande larvae to methyl jasmonate and cis-jasmone.

PubMed

Egger, Barbara; Koschier, Elisabeth H

2014-01-01

The larval stages of Frankliniella occidentalis Pergande (Thysanoptera: Thripidae) cause more direct feeding damage to plants than the adults. We, therefore, investigated the behaviour-modifying effects on second instar larvae of two jasmonic acid derivatives. The artificial application of methyl jasmonate and cis -jasmone, both at 1 % concentration, deterred the larvae from settling in a dual choice bean leaf disc assay. We observed a dose-dependent feeding deterrence of both jasmonates and calculated the concentration required to reduce the feeding damage by 50 % relative to the control treatment (FDC 50 ) for each jasmonate. The feeding damage was reduced by the application of cis -jasmone at 1 % concentration, but not by the jasmonates at the respective FDC 50 in no-choice leaf disc bioassays. However, significantly more larvae left jasmonate-treated whole potted bean plants by migrating to the soil compared with control plants. Our results may be exploited extending behavioural manipulation by using plant compounds in thrips control programmes to the full lifecycle of the pest. Plant compounds could be used in integrated and biological pest management strategies against F. occidentalis in combination with the application of various above and below ground control measures.
T3SS-dependent differential modulations of the jasmonic acid pathway in susceptible and resistant genotypes of Malus spp. challenged with Erwinia amylovora.

PubMed

Dugé De Bernonville, Thomas; Gaucher, Matthieu; Flors, Victor; Gaillard, Sylvain; Paulin, Jean-Pierre; Dat, James F; Brisset, Marie-Noëlle

2012-06-01

Fire blight is a bacterial disease of Maloideae caused by Erwinia amylovora (Ea). This necrogenic enterobacterium uses a type III secretion system (T3SS) to inject type III effectors into the plant cells to cause disease on its susceptible hosts, including economically important crops like apple and pear. The expressions of marker genes of the salicylic acid (SA) and jasmonic acid (JA) defense regulation pathways were monitored by RT-qPCR in leaves of two apple genotypes, one susceptible and one resistant, challenged with a wild type strain, a T3SS-deficient strain or water. The transcriptional data taken together with hormone level measurements indicated that the SA pathway was similarly induced in both apple genotypes during infection by Ea. On the contrary, the data clearly showed a strong T3SS-dependent down-regulation of the JA pathway in leaves of the susceptible genotype but not in those of the resistant one. Accordingly, methyl-jasmonate treated susceptible plants displayed an increased resistance to Ea. Bacterial mutant analysis indicated that JA manipulation by Ea mainly relies on the type III effector DspA/E. Taken together, our data suggest that the T3SS-dependent down-regulation of the JA pathway is a critical step in the infection process of Malus spp. by Ea. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Cyclic lipopeptide iturin A structure-dependently induces defense response in Arabidopsis plants by activating SA and JA signaling pathways.

PubMed

Kawagoe, Yumi; Shiraishi, Soma; Kondo, Hiroko; Yamamoto, Shoko; Aoki, Yoshinao; Suzuki, Shunji

2015-05-15

Iturin A is the most well studied antifungal cyclic lipopeptide produced by Bacillus species that are frequently utilized as biological control agents. Iturin A not only shows strong antifungal activity against phytopathogens but also induces defense response in plants, thereby reducing plant disease severity. Here we report the defense signaling pathways triggered by iturin A in Arabidopsis salicylic acid (SA) or jasmonic acid (JA)-insensitive mutants. Iturin A activated the transcription of defense genes PR1 and PDF1.2 through the SA and JA signaling pathways, respectively. The role of iturin A as an elicitor was dependent on the cyclization of the seven amino acids and/or the β-hydroxy fatty acid chain. The iturin A derivative peptide, NH2-(L-Asn)-(D-Tyr)-(D-Asn)-(L-Gln)-(L-Pro)-(D-Asn)-(L-Ser)-COOH, completely suppressed PR1 and PDF1.2 gene expression in wild Arabidopsis plants. The identification of target molecules binding to iturin A and its derivative peptide is expected to shed new light on defense response in plants through the SA and JA signaling pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

The oxylipin pathway in Arabidopsis.

PubMed

Creelman, Robert A; Mulpuri, Rao

2002-01-01

Oxylipins are acyclic or cyclic oxidation products derived from the catabolism of fatty acids which regulate many defense and developmental pathways in plants. The dramatic increase in the volume of publications and reviews on these compounds since 1997 documents the increasing interest in this compound and its role in plants. Research on this topic has solidified our understanding of the chemistry and biosynthetic pathways for oxylipin production. However, more information is still needed on how free fatty acids are produced and the role of beta-oxidation in the biosynthetic pathway for oxylipins. It is also becoming apparent that oxylipin content and composition changes during growth and development and during pathogen or insect attack. Oxylipins such as jasmonic acid (JA) or 12-oxo-phytodienoic acid modulate the expression of numerous genes and influence specific aspects of plant growth, development and responses to abiotic and biotic stresses. Although oxylipins are believed to act alone, several examples were presented to illustrate that JA-induced responses are modulated by the type and the nature of crosstalk with other signaling molecules such as ethylene and salicylic acid. How oxylipins cause changes in gene expression and instigate a physiological response is becoming understood with the isolation of mutations in both positive and negative regulators in the jasmonate signaling pathway and the use of cDNA microarrays.
The Oxylipin Pathway in Arabidopsis

PubMed Central

Creelman, Robert A.; Mulpuri, Rao

2002-01-01

Oxylipins are acyclic or cyclic oxidation products derived from the catabolism of fatty acids which regulate many defense and developmental pathways in plants. The dramatic increase in the volume of publications and reviews on these compounds since 1997 documents the increasing interest in this compound and its role in plants. Research on this topic has solidified our understanding of the chemistry and biosynthetic pathways for oxylipin production. However, more information is still needed on how free fatty acids are produced and the role of beta-oxidation in the biosynthetic pathway for oxylipins. It is also becoming apparent that oxylipin content and composition changes during growth and development and during pathogen or insect attack. Oxylipins such as jasmonic acid (JA) or 12-oxo-phytodienoic acid modulate the expression of numerous genes and influence specific aspects of plant growth, development and responses to abiotic and biotic stresses. Although oxylipins are believed to act alone, several examples were presented to illustrate that JA-induced responses are modulated by the type and the nature of crosstalk with other signaling molecules such as ethylene and salicylic acid. How oxylipins cause changes in gene expression and instigate a physiological response is becoming understood with the isolation of mutations in both positive and negative regulators in the jasmonate signaling pathway and the use of cDNA microarrays. PMID:22303193
Non-Smad signaling pathways.

PubMed

Mu, Yabing; Gudey, Shyam Kumar; Landström, Maréne

2012-01-01

Transforming growth factor-beta (TGFβ) is a key regulator of cell fate during embryogenesis and has also emerged as a potent driver of the epithelial-mesenchymal transition during tumor progression. TGFβ signals are transduced by transmembrane type I and type II serine/threonine kinase receptors (TβRI and TβRII, respectively). The activated TβR complex phosphorylates Smad2 and Smad3, converting them into transcriptional regulators that complex with Smad4. TGFβ also uses non-Smad signaling pathways such as the p38 and Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathways to convey its signals. Ubiquitin ligase tumor necrosis factor (TNF)-receptor-associated factor 6 (TRAF6) and TGFβ-associated kinase 1 (TAK1) have recently been shown to be crucial for the activation of the p38 and JNK MAPK pathways. Other TGFβ-induced non-Smad signaling pathways include the phosphoinositide 3-kinase-Akt-mTOR pathway, the small GTPases Rho, Rac, and Cdc42, and the Ras-Erk-MAPK pathway. Signals induced by TGFβ are tightly regulated and specified by post-translational modifications of the signaling components, since they dictate the subcellular localization, activity, and duration of the signal. In this review, we discuss recent findings in the field of TGFβ-induced responses by non-Smad signaling pathways.
The WRKY57 Transcription Factor Affects the Expression of Jasmonate ZIM-Domain Genes Transcriptionally to Compromise Botrytis cinerea Resistance.

PubMed

Jiang, Yanjuan; Yu, Diqiu

2016-08-01

Although necrotrophic pathogens cause many devastating plant diseases, our understanding of the plant defense response to them is limited. Here, we found that loss of function of WRKY57 enhanced the resistance of Arabidopsis (Arabidopsis thaliana) against Botrytis cinerea infection. Further investigation suggested that the negative regulation of WRKY57 against B cinerea depends on the jasmonic acid (JA) signaling pathway. Chromatin immunoprecipitation experiments revealed that WRKY57 directly binds to the promoters of JASMONATE ZIM-DOMAIN1 (JAZ1) and JAZ5, encoding two important repressors of the JA signaling pathway, and activates their transcription. In vivo and in vitro experiments demonstrated that WRKY57 interacts with nuclear-encoded SIGMA FACTOR BINDING PROTEIN1 (SIB1) and SIB2. Further experiments display that the same domain, the VQ motif, of SIB1 and SIB2 interact with WRKY33 and WRKY57. Moreover, transient transcriptional activity assays confirmed that WRKY57 and WRKY33 competitively regulate JAZ1 and JAZ5, SIB1 and SIB2 further enhance these competitions of WRKY57 to WRKY33. Therefore, coordinated regulation of Arabidopsis against B cinerea by transcription activators and repressors would benefit plants by allowing fine regulation of defense. © 2016 American Society of Plant Biologists. All Rights Reserved.
Downstream divergence of the ethylene signaling pathway for harpin-stimulated Arabidopsis growth and insect defense.

PubMed

Dong, Hong-Ping; Peng, Jianling; Bao, Zhilong; Meng, Xiangdong; Bonasera, Jean M; Chen, Guangyong; Beer, Steven V; Dong, Hansong

2004-11-01

Ethylene (ET) signal transduction may regulate plant growth and defense, depending on which components are recruited into the pathway in response to different stimuli. We report here that the ET pathway controls both insect resistance (IR) and plant growth enhancement (PGE) in Arabidopsis (Arabidopsis thaliana) plants responding to harpin, a protein produced by a plant pathogenic bacterium. PGE may result from spraying plant tops with harpin or by soaking seeds in harpin solution; the latter especially enhances root growth. Plants treated similarly develop resistance to the green peach aphid (Myzus persicae). The salicylic acid pathway, although activated by harpin, does not lead to PGE and IR. By contrast, PGE and IR are induced in both wild-type plants and genotypes that have defects in salicylic acid signaling. In response to harpin, levels of jasmonic acid (JA) decrease, and the COI1 gene, which is indispensable for JA signal transduction, is not expressed in wild-type plants. However, PGE and IR are stimulated in the JA-resistant mutant jar1-1. In the wild type, PGE and IR develop coincidently with increases in ET levels and the expression of several genes essential for ET signaling. The ET receptor gene ETR1 is required because both phenotypes are arrested in the etr1-1 mutant. Consistently, inhibition of ET perception nullifies the induction of both PGE and IR. The signal transducer EIN2 is required for IR, and EIN5 is required for PGE because IR and PGE are impaired correspondingly in the ein2-1 and ein5-1 mutants. Therefore, harpin activates ET signaling while conscribing EIN2 and EIN5 to confer IR and PGE, respectively.
Up-regulation of abscisic acid signaling pathway facilitates aphid xylem absorption and osmoregulation under drought stress.

PubMed

Guo, Huijuan; Sun, Yucheng; Peng, Xinhong; Wang, Qinyang; Harris, Marvin; Ge, Feng

2016-02-01

The activation of the abscisic acid (ABA) signaling pathway reduces water loss from plants challenged by drought stress. The effect of drought-induced ABA signaling on the defense and nutrition allocation of plants is largely unknown. We postulated that these changes can affect herbivorous insects. We studied the effects of drought on different feeding stages of pea aphids in the wild-type A17 of Medicago truncatula and ABA signaling pathway mutant sta-1. We examined the impact of drought on plant water status, induced plant defense signaling via the abscisic acid (ABA), jasmonic acid (JA), and salicylic acid (SA) pathways, and on the host nutritional quality in terms of leaf free amino acid content. During the penetration phase of aphid feeding, drought decreased epidermis/mesophyll resistance but increased mesophyll/phloem resistance of A17 but not sta-1 plants. Quantification of transcripts associated with ABA, JA and SA signaling indicated that the drought-induced up-regulation of ABA signaling decreased the SA-dependent defense but increased the JA-dependent defense in A17 plants. During the phloem-feeding phase, drought had little effect on the amino acid concentrations and the associated aphid phloem-feeding parameters in both plant genotypes. In the xylem absorption stage, drought decreased xylem absorption time of aphids in both genotypes because of decreased water potential. Nevertheless, the activation of the ABA signaling pathway increased water-use efficiency of A17 plants by decreasing the stomatal aperture and transpiration rate. In contrast, the water potential of sta-1 plants (unable to close stomata) was too low to support xylem absorption activity of aphids; the aphids on sta-1 plants had the highest hemolymph osmolarity and lowest abundance under drought conditions. Taken together this study illustrates the significance of cross-talk between biotic-abiotic signaling pathways in plant-aphid interaction, and reveals the mechanisms leading to alter
Up-regulation of abscisic acid signaling pathway facilitates aphid xylem absorption and osmoregulation under drought stress

PubMed Central

Guo, Huijuan; Sun, Yucheng; Peng, Xinhong; Wang, Qinyang; Harris, Marvin; Ge, Feng

2016-01-01

The activation of the abscisic acid (ABA) signaling pathway reduces water loss from plants challenged by drought stress. The effect of drought-induced ABA signaling on the defense and nutrition allocation of plants is largely unknown. We postulated that these changes can affect herbivorous insects. We studied the effects of drought on different feeding stages of pea aphids in the wild-type A17 of Medicago truncatula and ABA signaling pathway mutant sta-1. We examined the impact of drought on plant water status, induced plant defense signaling via the abscisic acid (ABA), jasmonic acid (JA), and salicylic acid (SA) pathways, and on the host nutritional quality in terms of leaf free amino acid content. During the penetration phase of aphid feeding, drought decreased epidermis/mesophyll resistance but increased mesophyll/phloem resistance of A17 but not sta-1 plants. Quantification of transcripts associated with ABA, JA and SA signaling indicated that the drought-induced up-regulation of ABA signaling decreased the SA-dependent defense but increased the JA-dependent defense in A17 plants. During the phloem-feeding phase, drought had little effect on the amino acid concentrations and the associated aphid phloem-feeding parameters in both plant genotypes. In the xylem absorption stage, drought decreased xylem absorption time of aphids in both genotypes because of decreased water potential. Nevertheless, the activation of the ABA signaling pathway increased water-use efficiency of A17 plants by decreasing the stomatal aperture and transpiration rate. In contrast, the water potential of sta-1 plants (unable to close stomata) was too low to support xylem absorption activity of aphids; the aphids on sta-1 plants had the highest hemolymph osmolarity and lowest abundance under drought conditions. Taken together this study illustrates the significance of cross-talk between biotic-abiotic signaling pathways in plant-aphid interaction, and reveals the mechanisms leading to alter
Jasmonate induction of the monoterpene linalool confers resistance to rice bacterial blight and its biosynthesis is regulated by JAZ protein in rice.

PubMed

Taniguchi, Shiduku; Hosokawa-Shinonaga, Yumi; Tamaoki, Daisuke; Yamada, Shoko; Akimitsu, Kazuya; Gomi, Kenji

2014-02-01

Jasmonic acid (JA) is involved in the regulation of host immunity in plants. Recently, we demonstrated that JA signalling has an important role in resistance to rice bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo) in rice. Here, we report that many volatile compounds accumulate in response to exogenous application of JA, including the monoterpene linalool. Expression of linalool synthase was up-regulated by JA. Vapour treatment with linalool induced resistance to Xoo, and transgenic rice plants overexpressing linalool synthase were more resistance to Xoo, presumably due to the up-regulation of defence-related genes in the absence of any treatment. JA-induced accumulation of linalool was regulated by OsJAZ8, a rice jasmonate ZIM-domain protein involving the JA signalling pathway at the transcriptional level, suggesting that linalool plays an important role in JA-induced resistance to Xoo in rice. © 2013 John Wiley & Sons Ltd.
Transcriptional Profiling of Sorghum Induced by Methyl Jasmonate, Salicylic Acid, and Aminocyclopropane Carboxylic Acid Reveals Cooperative Regulation and Novel Gene Responses1[w

PubMed Central

Salzman, Ron A.; Brady, Jeff A.; Finlayson, Scott A.; Buchanan, Christina D.; Summer, Elizabeth J.; Sun, Feng; Klein, Patricia E.; Klein, Robert R.; Pratt, Lee H.; Cordonnier-Pratt, Marie-Michèle; Mullet, John E.

2005-01-01

We have conducted a large-scale study of gene expression in the C4 monocot sorghum (Sorghum bicolor) L. Moench cv BTx623 in response to the signaling compounds salicylic acid (SA), methyl jasmonate (MeJA), and the ethylene precursor aminocyclopropane carboxylic acid. Expression profiles were generated from seedling root and shoot tissue at 3 and 27 h, using a microarray containing 12,982 nonredundant elements. Data from 102 slides and quantitative reverse transcription-PCR data on mRNA abundance from 171 genes were collected and analyzed and are here made publicly available. Numerous gene clusters were identified in which expression was correlated with particular signaling compound and tissue combinations. Many genes previously implicated in defense responded to the treatments, including numerous pathogenesis-related genes and most members of the phenylpropanoid pathway, and several other genes that may represent novel activities or pathways. Genes of the octadecanoic acid pathway of jasmonic acid (JA) synthesis were induced by SA as well as by MeJA. The resulting hypothesis that increased SA could lead to increased endogenous JA production was confirmed by measurement of JA content. Comparison of responses to SA, MeJA, and combined SA+MeJA revealed patterns of one-way and mutual antagonisms, as well as synergistic effects on regulation of some genes. These experiments thus help further define the transcriptional results of cross talk between the SA and JA pathways and suggest that a subset of genes coregulated by SA and JA may comprise a uniquely evolved sector of plant signaling responsive cascades. PMID:15863699
Priming of anti-herbivore defense in tomato by arbuscular mycorrhizal fungus and involvement of the jasmonate pathway.

PubMed

Song, Yuan Yuan; Ye, Mao; Li, Chuan You; Wang, Rui Long; Wei, Xiao Chen; Luo, Shi Ming; Zeng, Ren Sen

2013-07-01

Mycorrhizas play a vital role in soil fertility, plant nutrition, and resistance to environmental stresses. However, mycorrhizal effects on plant resistance to herbivorous insects and the related mechanisms are poorly understood. This study evaluated effects of root colonization of tomato (Solanum lycopersicum Mill.) by arbuscular mycorrhizal fungi (AMF) Glomus mosseae on plant defense responses against a chewing caterpillar Helicoverpa arimigera. Mycorrhizal inoculation negatively affected larval performance. Real time RT-PCR analyses showed that mycorrhizal inoculation itself did not induce transcripts of most genes tested. However, insect feeding on AMF pre-inoculated plants resulted in much stronger defense response induction of four defense-related genes LOXD, AOC, PI-I, and PI-II in the leaves of tomato plants relative to non-inoculated plants. Four tomato genotypes: a wild-type (WT) plant, a jasmonic acid (JA) biosynthesis mutant (spr2), a JA-signaling perception mutant (jai1), and a JA-overexpressing 35S::PS plant were used to determine the role of the JA pathway in AMF-primed defense. Insect feeding on mycorrhizal 35S::PS plants led to higher induction of defense-related genes relative to WT plants. However, insect feeding on mycorrhizal spr2 and jai1 mutant plants did not induce transcripts of these genes. Bioassays showed that mycorrhizal inoculation on spr2 and jai1 mutants did not change plant resistance against H. arimigera. These results indicates that mycorrhizal colonization could prime systemic defense responses in tomato upon herbivore attack, and that the JA pathway is involved in defense priming by AMF.
N,N-dimethyl hexadecylamine and related amines regulate root morphogenesis via jasmonic acid signaling in Arabidopsis thaliana.

PubMed

Raya-González, Javier; Velázquez-Becerra, Crisanto; Barrera-Ortiz, Salvador; López-Bucio, José; Valencia-Cantero, Eduardo

2017-05-01

Plant growth-promoting rhizobacteria are natural inhabitants of roots, colonize diverse monocot and dicot species, and affect several functional traits such as root architecture, adaptation to adverse environments, and protect plants from pathogens. N,N-dimethyl-hexadecylamine (C16-DMA) is a rhizobacterial amino lipid that modulates the postembryonic development of several plants, likely as part of volatile blends. In this work, we evaluated the bioactivity of C16-DMA and other related N,N-dimethyl-amines with varied length and found that inhibition of primary root growth was related to the length of the acyl chain. C16-DMA inhibited primary root growth affecting cell division and elongation, while promoting lateral root formation and root hair growth and density in Arabidopsis thaliana (Arabidopsis) wild-type (WT) seedlings. Interestingly, C16-DMA induced the expression of the jasmonic acid (JA)-responsive gene marker pLOX2:uidA, while JA-related mutants jar1, coi1-1, and myc2 affected on JA biosynthesis and perception, respectively, are compromised in C16-DMA responses. Comparison of auxin-regulated gene expression, root architectural changes in WT, and auxin-related mutants aux1-7, tir1/afb2/afb3, and arf7-1/arf19-1 to C16-DMA shows that the C16-DMA effects occur independently of auxin signaling. Together, these results reveal a novel class of aminolipids modulating root organogenesis via crosstalk with the JA signaling pathway.
A Catharanthus roseus BPF-1 homologue interacts with an elicitor-responsive region of the secondary metabolite biosynthetic gene Str and is induced by elicitor via a JA-independent signal transduction pathway.

PubMed

van der Fits, L; Zhang, H; Menke, F L; Deneka, M; Memelink, J

2000-11-01

Plants respond to pathogen attack by induction of various defence responses, including the biosynthesis of protective secondary metabolites. In Catharanthus roseus, the elicitor-induced expression of the terpenoid indole alkaloid biosynthetic gene Strictosidine synthase (Str) is mediated via the plant stress hormonejasmonate. In the promoters of several defence-related genes, cis-acting elements have been identified that are important for transcriptional regulation upon stress signals. Here we show that an upstream region in the Str promoter confers responsiveness to partially purified yeast elicitor and jasmonate. Yeast one-hybrid screening with this element as a bait identified a MYB-like protein, which shows high homology to parsley box P-binding factor-1 (PcBPF-1). In vitro analyses showed that the Str promoter fragment contained a novel binding site for BPF-1-like proteins with higher binding affinity than the previously described box P. CrBPF-1 mRNA accumulated rapidly in elicitor-treated C. roseus suspension cells, whereas no induction was observed with jasmonate. Inhibitor studies indicated that CrBPF-1 plays a role in an elicitor-responsive but jasmonate-independent signal transduction pathway, acting downstream of protein phosphorylation and calcium influx.
A Jasmonate ZIM-Domain Protein NaJAZd Regulates Floral Jasmonic Acid Levels and Counteracts Flower Abscission in Nicotiana attenuata Plants

PubMed Central

Oh, Youngjoo; Baldwin, Ian T.; Galis, Ivan

2013-01-01

Jasmonic acid is an important regulator of plant growth, development and defense. The jasmonate-ZIM domain (JAZ) proteins are key regulators in jasmonate signaling ubiquitously present in flowering plants but their functional annotation remains largely incomplete. Recently, we identified 12 putative JAZ proteins in native tobacco, Nicotiana attenuata, and initiated systematic functional characterization of these proteins by reverse genetic approaches. In this report, Nicotiana attenuata plants silenced in the expression of NaJAZd (irJAZd) by RNA interference were used to characterize NaJAZd function. Although NaJAZd transcripts were strongly and transiently up-regulated in the rosette leaves by simulated herbivory treatment, we did not observe strong defense-related phenotypes, such as altered herbivore performance or the constitutive accumulation of defense-related secondary metabolites in irJAZd plants compared to wild type plants, both in the glasshouse and the native habitat of Nicotiana attenuata in the Great Basin Desert, Utah, USA. Interestingly, irJAZd plants produced fewer seed capsules than did wild type plants as a result of increased flower abscission in later stages of flower development. The early- and mid-developmental stages of irJAZd flowers had reduced levels of jasmonic acid and jasmonoyl-L-isoleucine, while fully open flowers had normal levels, but these were impaired in NaMYB305 transcript accumulations. Previously, NaMYB305-silenced plants were shown to have strong flower abscission phenotypes and contained lower NECTARIN 1 transcript levels, phenotypes which are copied in irJAZd plants. We propose that the NaJAZd protein is required to counteract flower abscission, possibly by regulating jasmonic acid and jasmonoyl-L-isoleucine levels and/or expression of NaMYB305 gene in Nicotiana attenuata flowers. This novel insight into the function of JAZ proteins in flower and seed development highlights the diversity of functions played by jasmonates
Interactive Effects of Jasmonic Acid, Salicylic Acid, and Gibberellin on Induction of Trichomes in Arabidopsis1

PubMed Central

Traw, M. Brian; Bergelson, Joy

2003-01-01

Leaf trichomes protect plants from attack by insect herbivores and are often induced following damage. Hormonal regulation of this plant induction response has not been previously studied. In a series of experiments, we addressed the effects of artificial damage, jasmonic acid, salicylic acid, and gibberellin on induction of trichomes in Arabidopsis. Artificial damage and jasmonic acid caused significant increases in trichome production of leaves. The jar1-1 mutant exhibited normal trichome induction following treatment with jasmonic acid, suggesting that adenylation of jasmonic acid is not necessary. Salicylic acid had a negative effect on trichome production and consistently reduced the effect of jasmonic acid, suggesting negative cross-talk between the jasmonate and salicylate-dependent defense pathways. Interestingly, the effect of salicylic acid persisted in the nim1-1 mutant, suggesting that the Npr1/Nim1 gene is not downstream of salicylic acid in the negative regulation of trichome production. Last, we found that gibberellin and jasmonic acid had a synergistic effect on the induction of trichomes, suggesting important interactions between these two compounds. PMID:14551332
MATI, a Novel Protein Involved in the Regulation of Herbivore-Associated Signaling Pathways

PubMed Central

Santamaría, M. Estrella; Martinez, Manuel; Arnaiz, Ana; Ortego, Félix; Grbic, Vojislava; Diaz, Isabel

2017-01-01

The defense response of the plants against herbivores relies on a complex network of interconnected signaling pathways. In this work, we characterized a new key player in the response of Arabidopsis against the two-spotted spider mite Tetranychus urticae, the MATI (Mite Attack Triggered Immunity) gene. This gene was differentially induced in resistant Bla-2 strain relative to susceptible Kon Arabidopsis accessions after mite attack, suggesting a potential role in the control of spider mites. To study the MATI gene function, it has been performed a deep molecular characterization of the gene combined with feeding bioassays using modified Arabidopsis lines and phytophagous arthropods. The MATI gene belongs to a new gene family that had not been previously characterized. Biotic assays showed that it confers a high tolerance not only to T. urticae, but also to the chewing lepidopteran Spodoptera exigua. Biochemical analyses suggest that MATI encodes a protein involved in the accumulation of reducing agents upon herbivore attack to control plant redox homeostasis avoiding oxidative damage and cell death. Besides, molecular analyses demonstrated that MATI is involved in the modulation of different hormonal signaling pathways, affecting the expression of genes involved in biosynthesis and signaling of the jasmonic acid and salicylic acid hormones. The fact that MATI is also involved in defense through the modulation of the levels of photosynthetic pigments highlights the potential of MATI proteins to be exploited as biotechnological tools for pest control. PMID:28649257
The Arabidopsis KH-Domain RNA-Binding Protein ESR1 Functions in Components of Jasmonate Signalling, Unlinking Growth Restraint and Resistance to Stress

PubMed Central

Thatcher, Louise F.; Kamphuis, Lars G.; Hane, James K.; Oñate-Sánchez, Luis; Singh, Karam B.

2015-01-01

Glutathione S-transferases (GSTs) play important roles in the protection of cells against toxins and oxidative damage where one Arabidopsis member, GSTF8, has become a commonly used marker gene for early stress and defense responses. A GSTF8 promoter fragment fused to the luciferase reporter gene was used in a forward genetic screen for Arabidopsis mutants with up-regulated GSTF8 promoter activity. This identified the esr1-1 (enhanced stress response 1) mutant which also conferred increased resistance to the fungal pathogen Fusarium oxysporum. Through positional cloning, the ESR1 gene was found to encode a KH-domain containing RNA-binding protein (At5g53060). Whole transcriptome sequencing of esr1-1 identified altered expression of genes involved in responses to biotic and abiotic stimuli, hormone signaling pathways and developmental processes. In particular was an overall significant enrichment for jasmonic acid (JA) mediated processes in the esr1-1 down-regulated dataset. A subset of these genes were tested for MeJA inducibility and we found the expression of some but not all were reduced in esr1-1. The esr1-1 mutant was not impaired in other aspects of JA-signalling such as JA- sensitivity or development, suggesting ESR1 functions in specific components of the JA-signaling pathway. Examination of salicylic acid (SA) regulated marker genes in esr1-1 showed no increase in basal or SA induced expression suggesting repression of JA-regulated genes is not due to antagonistic SA-JA crosstalk. These results define new roles for KH-domain containing proteins with ESR1 unlinking JA-mediated growth and defense responses. PMID:25985302
The Arabidopsis KH-Domain RNA-Binding Protein ESR1 Functions in Components of Jasmonate Signalling, Unlinking Growth Restraint and Resistance to Stress.

PubMed

Thatcher, Louise F; Kamphuis, Lars G; Hane, James K; Oñate-Sánchez, Luis; Singh, Karam B

2015-01-01

Glutathione S-transferases (GSTs) play important roles in the protection of cells against toxins and oxidative damage where one Arabidopsis member, GSTF8, has become a commonly used marker gene for early stress and defense responses. A GSTF8 promoter fragment fused to the luciferase reporter gene was used in a forward genetic screen for Arabidopsis mutants with up-regulated GSTF8 promoter activity. This identified the esr1-1 (enhanced stress response 1) mutant which also conferred increased resistance to the fungal pathogen Fusarium oxysporum. Through positional cloning, the ESR1 gene was found to encode a KH-domain containing RNA-binding protein (At5g53060). Whole transcriptome sequencing of esr1-1 identified altered expression of genes involved in responses to biotic and abiotic stimuli, hormone signaling pathways and developmental processes. In particular was an overall significant enrichment for jasmonic acid (JA) mediated processes in the esr1-1 down-regulated dataset. A subset of these genes were tested for MeJA inducibility and we found the expression of some but not all were reduced in esr1-1. The esr1-1 mutant was not impaired in other aspects of JA-signalling such as JA- sensitivity or development, suggesting ESR1 functions in specific components of the JA-signaling pathway. Examination of salicylic acid (SA) regulated marker genes in esr1-1 showed no increase in basal or SA induced expression suggesting repression of JA-regulated genes is not due to antagonistic SA-JA crosstalk. These results define new roles for KH-domain containing proteins with ESR1 unlinking JA-mediated growth and defense responses.
[Research of mechanism of secondary metabolites of phenolic acids in Salvia miltiorrhiza hairy root induced by jasmonate].

PubMed

Li, Wenyuan; Gao, Wei; Zhao, Jing; Cui, Guanghong; Shao, Aijuan; Huang, Luqi

2012-01-01

To study the mechanism of secondary metabolites of some phenolic acids in the hairy roots of Salvia miltiorrhiza induced by methyl jasmonate. The hairy roots of S. miltiorrhiza were induced with methyl jasmonate (100 micromol x L(-1)) and collected at 0, 12, 24, 36 h after treatment. Real-time quantitative PCR was used for detecting the mRNA expression level of the key enzyme genes on the secondary metabolites pathway of rosmarinic acid, while a LC-MS method was developed to determine the content of rosmarinic acid, caffeic acid and salvianolic acid B. The concentration of phenolic acids grew up and accumulated quickly in the hairy roots with exogenous signal molecule MJ induced, and it was showed that the content of CA and RA reached the maximum after 24 h and the content of LAB reached the maximum in 36 h by MJ induced. The induction mechanism may be activated with different levels of RA synthesis in PAL, 4CL, C4H genes on the key enzyme phenylalanine pathway and TAT, HPPR genes on tyrosine pathway. The time of gene expression was different, among them, 4CL and PAL genes were more important. In a word, the result can provide some basis data about the mechanism of secondary metabolites of phenolic acids for further research.
Heterotrimeric G proteins-mediated resistance to necrotrophic pathogens includes mechanisms independent of salicylic acid-, jasmonic acid/ethylene- and abscisic acid-mediated defense signaling.

PubMed

Trusov, Yuri; Sewelam, Nasser; Rookes, James Edward; Kunkel, Matt; Nowak, Ekaterina; Schenk, Peer Martin; Botella, José Ramón

2009-04-01

Heterotrimeric G proteins are involved in the defense response against necrotrophic fungi in Arabidopsis. In order to elucidate the resistance mechanisms involving heterotrimeric G proteins, we analyzed the effects of the Gβ (subunit deficiency in the mutant agb1-2 on pathogenesis-related gene expression, as well as the genetic interaction between agb1-2 and a number of mutants of established defense pathways. Gβ-mediated signaling suppresses the induction of salicylic acid (SA)-, jasmonic acid (JA)-, ethylene (ET)- and abscisic acid (ABA)-dependent genes during the initial phase of the infection with Fusarium oxysporum (up to 48 h after inoculation). However, at a later phase it enhances JA/ET-dependent genes such as PDF1.2 and PR4. Quantification of the Fusarium wilt symptoms revealed that Gβ- and SA-deficient mutants were more susceptible than wild-type plants, whereas JA- and ET-insensitive and ABA-deficient mutants demonstrated various levels of resistance. Analysis of the double mutants showed that the Gβ-mediated resistance to F. oxysporum and Alternaria brassicicola was mostly independent of all of the previously mentioned pathways. However, the progressive decay of agb1-2 mutants was compensated by coi1-21 and jin1-9 mutations, suggesting that at this stage of F. oxysporum infection Gβ acts upstream of COI1 and ATMYC2 in JA signaling. © 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd.
Memory responses of jasmonic acid-associated Arabidopsis genes to a repeated dehydration stress.

PubMed

Liu, Ning; Staswick, Paul E; Avramova, Zoya

2016-11-01

Dehydration stress activates numerous genes co-regulated by diverse signaling pathways. Upon repeated exposures, however, a subset of these genes does not respond maintaining instead transcription at their initial pre-stressed levels ('revised-response' genes). Most of these genes are involved in jasmonic acid (JA) biosynthesis, JA-signaling and JA-mediated stress responses. How these JA-associated genes are regulated to provide different responses to similar dehydration stresses is an enigma. Here, we investigate molecular mechanisms that contribute to this transcriptional behavior. The memory-mechanism is stress-specific: one exposure to dehydration stress or to abscisic acid (ABA) is required to prevent transcription in the second. Both ABA-mediated and JA-mediated pathways are critical for the activation of these genes, but the two signaling pathways interact differently during a single or multiple encounters with dehydration stress. Synthesis of JA during the first (S1) but not the second dehydration stress (S2) accounts for the altered transcriptional responses. We propose a model for these memory responses, wherein lack of MYC2 and of JA synthesis in S2 is responsible for the lack of expression of downstream genes. The similar length of the memory displayed by different memory-type genes suggests biological relevance for transcriptional memory as a gene-regulating mechanism during recurring bouts of drought. © 2016 John Wiley & Sons Ltd.

The sesquiterpene botrydial produced by Botrytis cinerea induces the hypersensitive response on plant tissues and its action is modulated by salicylic acid and jasmonic acid signaling.

PubMed

Rossi, Franco Rubén; Gárriz, Andrés; Marina, María; Romero, Fernando Matías; Gonzalez, María Elisa; Collado, Isidro González; Pieckenstain, Fernando Luis

2011-08-01

Botrytis cinerea, as a necrotrophic fungus, kills host tissues and feeds on the remains. This fungus is able to induce the hypersensitive response (HR) on its hosts, thus taking advantage on the host's defense machinery for generating necrotic tissues. However, the identity of HR effectors produced by B. cinerea is not clear. The aim of this work was to determine whether botrydial, a phytotoxic sesquiterpene produced by B. cinerea, is able to induce the HR on plant hosts, using Arabidopsis thaliana as a model. Botrydial induced the expression of the HR marker HSR3, callose deposition, and the accumulation of reactive oxygen species and phenolic compounds. Botrydial also induced the expression of PR1 and PDF1.2, two pathogenesis-related proteins involved in defense responses regulated by salicylic acid (SA) and jasmonic acid (JA), respectively. A. thaliana and tobacco plants defective in SA signaling were more resistant to botrydial than wild-type plants, as opposed to A. thaliana plants defective in JA signaling, which were more sensitive. It can be concluded that botrydial induces the HR on its hosts and its effects are modulated by host signaling pathways mediated by SA and JA.
Ozone sensitivity in hybrid poplar correlates with insensitivity to both salicylic acid and jasmonic acid. The role of programmed cell death in lesion formation.

PubMed

Koch, J R; Creelman, R A; Eshita, S M; Seskar, M; Mullet, J E; Davis, K R

2000-06-01

Our earlier studies demonstrated that the ozone-sensitive hybrid poplar clone NE-388 displays an attenuated level of ozone-, wound-, and phytopathogen-induced defense gene expression. To determine if this reduced gene activation involves signal transduction pathways dependent on salicylic acid (SA) and/or jasmonic acid (JA), we compared the responses of NE-388 and an ozone-tolerant clone, NE-245, to these signal molecules. JA levels increased in both clones in response to ozone, but only minimal increases in SA levels were measured for either clone. Treatment with SA and methyl jasmonate induced defense gene expression only in NE-245, indicating that NE-388 is insensitive to these signal molecules. DNA fragmentation, an indicator of programmed cell death (PCD), was detected in NE-245 treated with either ozone or an avirulent phytopathogen, but was not detected in NE-388. We conclude that these clones undergo two distinct mechanisms of ozone-induced lesion formation. In NE-388, lesions appear to be due to toxic cell death resulting from a limited ability to perceive and subsequently activate SA- and/or JA-mediated antioxidant defense responses. In NE-245, SA-dependent PCD precedes lesion formation via a process related to the PCD pathway activated by phytopathogenic bacteria. These results support the hypothesis that ozone triggers a hypersensitive response.
Hormone crosstalk in plant disease and defense: more than just jasmonate-salicylate antagonism.

PubMed

Robert-Seilaniantz, Alexandre; Grant, Murray; Jones, Jonathan D G

2011-01-01

Until recently, most studies on the role of hormones in plant-pathogen interactions focused on salicylic acid (SA), jasmonic acid (JA), and ethylene (ET). It is now clear that pathogen-induced modulation of signaling via other hormones contributes to virulence. A picture is emerging of complex crosstalk and induced hormonal changes that modulate disease and resistance, with outcomes dependent on pathogen lifestyles and the genetic constitution of the host. Recent progress has revealed intriguing similarities between hormone signaling mechanisms, with gene induction responses often achieved by derepression. Here, we report on recent advances, updating current knowledge on classical defense hormones SA, JA, and ET, and the roles of auxin, abscisic acid (ABA), cytokinins (CKs), and brassinosteroids in molding plant-pathogen interactions. We highlight an emerging theme that positive and negative regulators of these disparate hormone signaling pathways are crucial regulatory targets of hormonal crosstalk in disease and defense. Copyright © 2011 by Annual Reviews. All rights reserved.
Regulation of growth-defense balance by the JASMONATE ZIM-DOMAIN (JAZ)-MYC transcriptional module

DOE Office of Scientific and Technical Information (OSTI.GOV)

Major, Ian T.; Yoshida, Yuki; Campos, Marcelo L.

The plant hormone jasmonate (JA) promotes the degradation of JASMONATE ZIM-DOMAIN (JAZ) proteins to relieve repression on diverse transcription factors (TFs) that execute JA responses. However, little is known about how combinatorial complexity among JAZ–TF interactions maintains control over myriad aspects of growth, development, reproduction, and immunity. We used loss-of-function mutations to define epistatic interactions within the core JA signaling pathway and to investigate the contribution of MYC TFs to JA responses in Arabidopsis thaliana. Constitutive JA signaling in a jaz quintuple mutant (jazQ) was largely eliminated by mutations that block JA synthesis or perception. Comparison of jazQ and amore » jazQ myc2 myc3 myc4 octuple mutant validated known functions of MYC2/3/4 in root growth, chlorophyll degradation,and susceptibility to the pathogen Pseudomonas syringae. We found that MYC TFs also control both the enhanced resistance of jazQ leaves to insect herbivory and restricted leaf growth of jazQ. Epistatic transcriptional profiles mirrored these phenotypes and further showed that triterpenoid biosynthetic and glucosinolate catabolic genes are up-regulated in jazQ independently of MYC TFs. Lastly, our study highlights the utility of genetic epistasis to unravel the complexities of JAZ–TF interactions and demonstrates that MYC TFs exert master control over a JAZ-repressible transcriptional hierarchy that governs growth–defense balance.« less
Regulation of growth-defense balance by the JASMONATE ZIM-DOMAIN (JAZ)-MYC transcriptional module

DOE PAGES

Major, Ian T.; Yoshida, Yuki; Campos, Marcelo L.; ...

2017-06-26

The plant hormone jasmonate (JA) promotes the degradation of JASMONATE ZIM-DOMAIN (JAZ) proteins to relieve repression on diverse transcription factors (TFs) that execute JA responses. However, little is known about how combinatorial complexity among JAZ–TF interactions maintains control over myriad aspects of growth, development, reproduction, and immunity. We used loss-of-function mutations to define epistatic interactions within the core JA signaling pathway and to investigate the contribution of MYC TFs to JA responses in Arabidopsis thaliana. Constitutive JA signaling in a jaz quintuple mutant (jazQ) was largely eliminated by mutations that block JA synthesis or perception. Comparison of jazQ and amore » jazQ myc2 myc3 myc4 octuple mutant validated known functions of MYC2/3/4 in root growth, chlorophyll degradation,and susceptibility to the pathogen Pseudomonas syringae. We found that MYC TFs also control both the enhanced resistance of jazQ leaves to insect herbivory and restricted leaf growth of jazQ. Epistatic transcriptional profiles mirrored these phenotypes and further showed that triterpenoid biosynthetic and glucosinolate catabolic genes are up-regulated in jazQ independently of MYC TFs. Lastly, our study highlights the utility of genetic epistasis to unravel the complexities of JAZ–TF interactions and demonstrates that MYC TFs exert master control over a JAZ-repressible transcriptional hierarchy that governs growth–defense balance.« less
Jasmonic acid-amino acid conjugation enzyme assays.

PubMed

Rowe, Martha L; Staswick, Paul E

2013-01-01

Jasmonic acid (JA) is activated for signaling by its conjugation to isoleucine (Ile) through an amide linkage. The Arabidopsis thaliana JASMONIC ACID RESISTANT1 (JAR1) enzyme carries out this Mg-ATP-dependent reaction in two steps, adenylation of the free carboxyl of JA, followed by condensation of the activated group to Ile. This chapter details the protocols used to detect and quantify the enzymatic activity obtained from a glutathione-S-transferase:JAR1 fusion protein produced in Escherichia coli, including an isotope exchange assay for the adenylation step and assays for the complete reaction that involve the high-performance liquid chromatography quantitation of adenosine monophosphate, a stoichiometric by-product of the reaction, and detection of the conjugation product by thin-layer chromatography or gas -chromatography/mass spectrometry.
Chloroplast Galactolipids: The Link Between Photosynthesis, Chloroplast Shape, Jasmonates, Phosphate Starvation and Freezing Tolerance.

PubMed

Li, Hsou-Min; Yu, Chun-Wei

2018-06-01

Monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) together constitute approximately 80% of chloroplast lipids. Apart from facilitating the photosynthesis light reaction in the thylakoid membrane, these two lipids are important for maintaining chloroplast morphology and for plant survival under abiotic stresses such as phosphate starvation and freezing. Recently it was shown that severe growth retardation phenotypes of the DGDG-deficient mutant dgd1 were due to jasmonate overproduction, linking MGDG and DGDG homeostasis with phytohormone production and suggesting MGDG as a major substrate for jasmonate biosynthesis. Induction of jasmonate synthesis and jasmonic acid (JA) signaling was also observed under conditions of phosphate starvation. We hypothesize that when DGDG is recruited to substitute for phospholipids in extraplastidic membranes during phosphate deficiency, the altered MGDG to DGDG ratio in the chloroplast envelope triggers the conversion of galactolipids into jasmonates. The conversion may contribute to rebalancing the MGDG to DGDG ratio rapidly to maintain chloroplast shape, and jasmonate production can reduce the growth rate and enhance predator deterrence. We also hypothesize that other conditions, such as suppression of dgd1 phenotypes by trigalactosyldiacylglycerol (tgd) mutations, may all be linked to altered jasmonate production, indicating that caution should be exercised when interpreting phenotypes caused by conditions that may alter the MGDG to DGDG ratio at the chloroplast envelope.
Induction of Jasmonic Acid-Associated Defenses by Thrips Alters Host Suitability for Conspecifics and Correlates with Increased Trichome Densities in Tomato

PubMed Central

Klinkhamer, Peter G.L.; Leiss, Kirsten A.

2017-01-01

Plant defenses inducible by herbivorous arthropods can determine performance of subsequent feeding herbivores. We investigated how infestation of tomato (Solanum lycopersicum) plants with the Western flower thrips (Frankliniella occidentalis) alters host plant suitability and foraging decisions of their conspecifics. We explored the role of delayed-induced jasmonic acid (JA)-mediated plant defense responses in thrips preference by using the tomato mutant def-1, impaired in JA biosynthesis. In particular, we investigated the effect of thrips infestation on trichome-associated tomato defenses. The results showed that when offered a choice, thrips preferred non-infested plants over infested wild-type plants, while no differences were observed in def-1. Exogenous application of methyl jasmonate restored the repellency effect in def-1. Gene expression analysis showed induction of the JA defense signaling pathway in wild-type plants, while activating the ethylene signaling pathway in both genotypes. Activation of JA defenses led to increases in type-VI leaf glandular trichome densities in the wild type, augmenting the production of trichome-associated volatiles, i.e. terpenes. Our study revealed that plant-mediated intraspecific interactions between thrips are determined by JA-mediated defenses in tomato. We report that insects can alter not only trichome densities but also the allelochemicals produced therein, and that this response might depend on the magnitude and/or type of the induction. PMID:28158865
Ozone Sensitivity in Hybrid Poplar Correlates with Insensitivity to Both Salicylic Acid and Jasmonic Acid. The Role of Programmed Cell Death in Lesion Formation1

PubMed Central

Koch, Jennifer Riehl; Creelman, Robert A.; Eshita, Steven M.; Seskar, Mirjana; Mullet, John E.; Davis, Keith R.

2000-01-01

Our earlier studies demonstrated that the ozone-sensitive hybrid poplar clone NE-388 displays an attenuated level of ozone-, wound-, and phytopathogen-induced defense gene expression. To determine if this reduced gene activation involves signal transduction pathways dependent on salicylic acid (SA) and/or jasmonic acid (JA), we compared the responses of NE-388 and an ozone-tolerant clone, NE-245, to these signal molecules. JA levels increased in both clones in response to ozone, but only minimal increases in SA levels were measured for either clone. Treatment with SA and methyl jasmonate induced defense gene expression only in NE-245, indicating that NE-388 is insensitive to these signal molecules. DNA fragmentation, an indicator of programmed cell death (PCD), was detected in NE-245 treated with either ozone or an avirulent phytopathogen, but was not detected in NE-388. We conclude that these clones undergo two distinct mechanisms of ozone-induced lesion formation. In NE-388, lesions appear to be due to toxic cell death resulting from a limited ability to perceive and subsequently activate SA- and/or JA-mediated antioxidant defense responses. In NE-245, SA-dependent PCD precedes lesion formation via a process related to the PCD pathway activated by phytopathogenic bacteria. These results support the hypothesis that ozone triggers a hypersensitive response. PMID:10859179
Role of β-Oxidation in Jasmonate Biosynthesis and Systemic Wound Signaling in TomatoW⃞

PubMed Central

Li, Chuanyou; Schilmiller, Anthony L.; Liu, Guanghui; Lee, Gyu In; Jayanty, Sastry; Sageman, Carolyn; Vrebalov, Julia; Giovannoni, James J.; Yagi, Kaori; Kobayashi, Yuichi; Howe, Gregg A.

2005-01-01

Jasmonic acid (JA) is a lipid-derived signal that regulates plant defense responses to biotic stress. Here, we report the characterization of a JA-deficient mutant of tomato (Lycopersicon esculentum) that lacks local and systemic expression of defensive proteinase inhibitors (PIs) in response to wounding. Map-based cloning studies demonstrated that this phenotype results from loss of function of an acyl-CoA oxidase (ACX1A) that catalyzes the first step in the peroxisomal β-oxidation stage of JA biosynthesis. Recombinant ACX1A exhibited a preference for C12 and C14 straight-chain acyl-CoAs and also was active in the metabolism of C18 cyclopentanoid-CoA precursors of JA. The overall growth, development, and reproduction of acx1 plants were similar to wild-type plants. However, the mutant was compromised in its defense against tobacco hornworm (Manduca sexta) attack. Grafting experiments showed that loss of ACX1A function disrupts the production of the transmissible signal for wound-induced PI expression but does not affect the recognition of this signal in undamaged responding leaves. We conclude that ACX1A is essential for the β-oxidation stage of JA biosynthesis and that JA or its derivatives is required both for antiherbivore resistance and the production of the systemic wound signal. These findings support a role for peroxisomes in the production of lipid-based signaling molecules that promote systemic defense responses. PMID:15722469
Interaction of plant cell signaling molecules, salicylic acid and jasmonic acid, with the mitochondria of Helicoverpa armigera.

PubMed

Akbar, S M D; Sharma, H C; Jayalakshmi, S K; Sreeramulu, K

2012-02-01

The cotton bollworm, Helicoverpa armigera is a polyphagous pest in Asia, Africa, and the Mediterranean Europe. Salicylic acid (SA) and jasmonic acid (JA) are the cell signaling molecules produced in response to insect attack in plants. The effect of these signaling molecules was investigated on the oxidative phosphorylation and oxidative stress of H. armigera. SA significantly inhibited the state III and state IV respiration, respiratory control index (RCI), respiratory complexes I and II, induced mitochondrial swelling, and cytochrome c release in vitro. Under in vivo conditions, SA induced state IV respiration as well as oxidative stress in time- and dose-dependent manner, and also inhibited the larval growth. In contrast, JA did not affect the mitochondrial respiration and oxidative stress. SA affected the growth and development of H. armigera, in addition to its function as signaling molecules involved in both local defense reactions at feeding sites and the induction of systemic acquired resistance in plants.
Jasmonic acid-isoleucine formation in grapevine (Vitis vinifera L.) by two enzymes with distinct transcription profiles.

PubMed

Böttcher, Christine; Burbidge, Crista A; di Rienzo, Valentina; Boss, Paul K; Davies, Christopher

2015-07-01

The plant hormone jasmonic acid (JA) is essential for stress responses and the formation of reproductive organs, but its role in fruit development and ripening is unclear. Conjugation of JA to isoleucine is a crucial step in the JA signaling pathway since only JA-Ile is recognized by the jasmonate receptor. The conjugation reaction is catalyzed by JA-amido synthetases, belonging to the family of Gretchen Hagen3 (GH3) proteins. Here, in vitro studies of two grapevine (Vitis vinifera L. cv Shiraz) GH3 enzymes, VvGH3-7 and VvGH3-9, demonstrated JA-conjugating activities with an overlapping range of amino acid substrates, including isoleucine. Expression studies of the corresponding genes in grape berries combined with JA and JA-Ile measurements suggested a primary role for JA signaling in fruit set and cell division and did not support an involvement of JA in the ripening process. In response to methyl JA (MeJA) treatment, and in wounded and unwounded (distal) leaves, VvGH3-9 transcripts accumulated, indicating a participation in the JA response. In contrast, VvGH3-7 was unresponsive to MeJA and local wounding, demonstrating a differential transcriptional regulation of VvGH3-7 and VvGH3-9. The transient induction of VvGH3-7 in unwounded, distal leaves was suggestive of the involvement of an unknown mobile wound signal. © 2014 Institute of Botany, Chinese Academy of Sciences.
Resistance of Cultivated Tomato to Cell Content-Feeding Herbivores Is Regulated by the Octadecanoid-Signaling Pathway1

PubMed Central

Li, Chuanyou; Williams, Mark M.; Loh, Ying-Tsu; Lee, Gyu In; Howe, Gregg A.

2002-01-01

The octadecanoid signaling pathway has been shown to play an important role in plant defense against various chewing insects and some pathogenic fungi. Here, we examined the interaction of a cell-content feeding arachnid herbivore, the two-spotted spider mite (Tetranychus urticae Koch), with cultivated tomato (Lycopersicon esculentum) and an isogenic mutant line (defenseless-1 [def-1]) that is deficient in the biosynthesis of the octadecanoid pathway-derived signal, jasmonic acid (JA). Spider mite feeding and fecundity on def-1 plants was significantly greater than on wild-type plants. Decreased resistance of def-1 plants was correlated with reduced JA accumulation and expression of defensive proteinase inhibitor (PI) genes, which were induced in mite-damaged wild-type leaves. Treatment of def-1 plants with methyl-JA restored resistance to spider mite feeding and reduced the fecundity of female mites. Plants expressing a 35S::prosystemin transgene that constitutively activates the octadecanoid pathway in a Def-1-dependent manner were highly resistant to attack by spider mites and western flower thrips (Frankliniella occidentalis), another cell-content feeder of economic importance. These findings indicate that activation of the octadecanoid signaling pathway promotes resistance of tomato to a broad spectrum of herbivores. The techniques of amplified fragment length polymorphism (AFLP) and bulk segregant analysis were used to map the Def-1 gene to a region on the long arm of chromosome 3 that is genetically separable from the map position of known JA biosynthetic genes. Tight linkage of Def-1 to a T-DNA insertion harboring the maize (Zea mays) Dissociation transposable element suggests a strategy for directed transposon tagging of the gene. PMID:12226528
Jasmonates trigger prey-induced formation of 'outer stomach' in carnivorous sundew plants.

PubMed

Nakamura, Yoko; Reichelt, Michael; Mayer, Veronika E; Mithöfer, Axel

2013-05-22

It has been widely accepted that the growth-related phytohormone auxin is the endogenous signal that initiates bending movements of plant organs. In 1875, Charles Darwin described how the bending movement of leaves in carnivorous sundew species formed an 'outer stomach' that allowed the plants to enclose and digest captured insect prey. About 100 years later, auxin was suggested to be the factor responsible for this movement. We report that prey capture induces both leaf bending and the accumulation of defence-related jasmonate phytohormones. In Drosera capensis fed with fruitflies, within 3 h after prey capture and simultaneous with leaf movement, we detected an increase in jasmonic acid and its isoleucine conjugate. This accumulation was spatially restricted to the bending segment of the leaves. The application of jasmonates alone was sufficient to trigger leaf bending. Only living fruitflies or the body fluids of crushed fruitflies induced leaf curvature; neither dead flies nor mechanical treatment had any effect. Our findings strongly suggest that the formation of the 'outer stomach' in Drosera is a chemonastic movement that is triggered by accumulation of endogenous jasmonates. These results suggest that in carnivorous sundew plants the jasmonate cascade might have been adapted to facilitate carnivory rather than to defend against herbivores.
Modularized TGFbeta-Smad Signaling Pathway

NASA Technical Reports Server (NTRS)

Li, Yongfeng; Wang, M.; Carra, C.; Cucinotta, F. A.

2011-01-01

The Transforming Growth Factor beta (TGFbeta) signaling pathway is a prominent regulatory signaling pathway controlling various important cellular processes. It can be induced by several factors, including ionizing radiation. It is regulated by Smads in a negative feedback loop through promoting increases in the regulatory Smads in the cell nucleus, and subsequent expression of inhibitory Smad, Smad7 to form a ubiquitin ligase with Smurf targeting active TGF receptors for degradation. In this work, we proposed a mathematical model to study the radiation-induced Smad-regulated TGF signaling pathway. By modularization, we are able to analyze each module (subsystem) and recover the nonlinear dynamics of the entire network system. Meanwhile the excitability, a common feature observed in the biological systems, along the TGF signaling pathway is discussed by mathematical analysis and numerical simulation.
Host and non-host pathogens elicit different jasmonate/ethylene responses in Arabidopsis.

PubMed

Zimmerli, Laurent; Stein, Mónica; Lipka, Volker; Schulze-Lefert, Paul; Somerville, Shauna

2004-12-01

Arabidopsis does not support the growth and asexual reproduction of the barley pathogen, Blumeria graminis f. sp. hordei Bgh). A majority of germlings fail to penetrate the epidermal cell wall and papillae. To gain additional insight into this interaction, we determined whether the salicylic acid (SA) or jasmonate (JA)/ethylene (ET) defence pathways played a role in blocking barley powdery mildew infections. Only the eds1 mutant and NahG transgenics supported a modest increase in penetration success by the barley powdery mildew. We also compared the global gene expression patterns of Arabidopsis inoculated with the non-host barley powdery mildew to those inoculated with a virulent, host powdery mildew, Erysiphe cichoracearum. Genes repressed by inoculations with non-host and host powdery mildews relative to non-inoculated control plants accounted for two-thirds of the differentially expressed genes. A majority of these genes encoded components of photosynthesis and general metabolism. Consistent with this observation, Arabidopsis growth was inhibited following inoculation with Bgh, suggesting a shift in resource allocation from growth to defence. A number of defence-associated genes were induced during both interactions. These genes likely are components of basal defence responses, which do not effectively block host powdery mildew infections. In addition, genes encoding defensins, anti-microbial peptides whose expression is under the control of the JA/ET signalling pathway, were induced exclusively by non-host pathogens. Ectopic activation of JA/ET signalling protected Arabidopsis against two biotrophic host pathogens. Taken together, these data suggest that biotrophic host pathogens must either suppress or fail to elicit the JA/ET signal transduction pathway.
Jasmonate-Dependent Induction of Indole Glucosinolates in Arabidopsis by Culture Filtrates of the Nonspecific Pathogen Erwinia carotovora1

PubMed Central

Brader, Günter; Tas, Éva; Palva, E. Tapio

2001-01-01

Elicitors from the plant pathogen Erwinia carotovora trigger coordinate induction of the tryptophan (Trp) biosynthesis pathway and Trp oxidizing genes in Arabidopsis. To elucidate the biological role of such pathogen-induced activation we characterized the production of secondary defense metabolites such as camalexin and indole glucosinolates derived from precursors of this pathway. Elicitor induction was followed by a specific increase in 3-indolylmethylglucosinolate (IGS) content, but only a barely detectable accumulation of the indole-derived phytoalexin camalexin. The response is mediated by jasmonic acid as shown by lack of IGS induction in the jasmonate-insensitive mutant coi1-1. In accordance with this, methyl jasmonate was able to trigger IGS accumulation in Arabidopsis. In contrast, ethylene and salicylic acid seem to play a minor role in the response. They did not trigger alterations in IGS levels, and methyl jasmonate- or elicitor-induced IGS accumulation in NahG and ethylene-insensitive ein2-1 mutant plants was similar as in the wild type. The breakdown products of IGS and other glucosinolates were able to inhibit growth of E. carotovora. The results suggest that IGS is of importance in the defense against bacterial pathogens. PMID:11402212
Effects of Methyl Jasmonate on the Composition of Volatile Compounds in Pyropia yezoensis

NASA Astrophysics Data System (ADS)

He, Lihong; Wang, Liang; Wang, Linfang; Shen, Songdong

2018-04-01

Volatile organic compounds in marine algae have been reported to comprise characteristic flavor of algae and play an important role in their growth, development and defensive response. Yet their biogeneration remain largely unknown. Here we studied the composition of volatile compouds in Pyropia yezoensis and their variations in response to methyl jasmonate (MeJA) and diethyldithiocarbamic acid (DIECA) treatment using gas chromatography-mass spectrometry (GC-MS). A total of 44 compounds belonging to the following chemical classes (n) were identified, including aldehydes (11), alcohols (8), acids and esters (6), alkanes (5), ketones (5), alkenes (3), and S- or N-containing miscellaneous compounds (6). External treatment with plant hormone MeJA increased the content of 1-dodecanol, 4-heptenal, and 2-propenoic acid-2-methyl dodecylester, but decreased the content of phytol, 3-heptadecene, 2-pentadecanone, and isophytol. When pretreated with DIECA, an inhibitor of the octadecanoid pathway leading to the biosynthesis of endogeneous jasmonates and some secondary metabolites, phytol and isophytol were increased, while 4-heptenal, 1-dodecanol, and 2-propenoic acid-2-methyl dodecylester were decreased, both of which were negatively correlated with their variations under MeJA treatment. Collectively, these results suggest that MeJA does affect the volatile composition of P. yezoensis, and the octadecanoid pathway together with endogenous jasmonate pathway may be involved in the biosynthesis of volatile compounds, thereby providing some preliminary envision on the composition and biogeneration of volatile compounds in P. yezoensis.
Salicylic Acid and Jasmonic Acid Pathways are Activated in Spatially Different Domains Around the Infection Site During Effector-Triggered Immunity in Arabidopsis thaliana.

PubMed

Betsuyaku, Shigeyuki; Katou, Shinpei; Takebayashi, Yumiko; Sakakibara, Hitoshi; Nomura, Nobuhiko; Fukuda, Hiroo

2018-01-01

The innate immune response is, in the first place, elicited at the site of infection. Thus, the host response can be different among the infected cells and the cells surrounding them. Effector-triggered immunity (ETI), a form of innate immunity in plants, is triggered by specific recognition between pathogen effectors and their corresponding plant cytosolic immune receptors, resulting in rapid localized cell death known as hypersensitive response (HR). HR cell death is usually limited to a few cells at the infection site, and is surrounded by a few layers of cells massively expressing defense genes such as Pathogenesis-Related Gene 1 (PR1). This virtually concentric pattern of the cellular responses in ETI is proposed to be regulated by a concentration gradient of salicylic acid (SA), a phytohormone accumulated around the infection site. Recent studies demonstrated that jasmonic acid (JA), another phytohormone known to be mutually antagonistic to SA in many cases, is also accumulated in and required for ETI, suggesting that ETI is a unique case. However, the molecular basis for this uniqueness remained largely to be solved. Here, we found that, using intravital time-lapse imaging, the JA signaling pathway is activated in the cells surrounding the central SA-active cells around the infection sites in Arabidopsis thaliana. This distinct spatial organization explains how these two phythormone pathways in a mutually antagonistic relationship can be activated simultaneously during ETI. Our results re-emphasize that the spatial consideration is a key strategy to gain mechanistic insights into the apparently complex signaling cross-talk in immunity. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.
Multilayered Organization of Jasmonate Signalling in the Regulation of Root Growth

PubMed Central

Gasperini, Debora; Chételat, Aurore; Acosta, Ivan F.; Goossens, Jonas; Pauwels, Laurens; Goossens, Alain; Dreos, René; Alfonso, Esteban; Farmer, Edward E.

2015-01-01

Physical damage can strongly affect plant growth, reducing the biomass of developing organs situated at a distance from wounds. These effects, previously studied in leaves, require the activation of jasmonate (JA) signalling. Using a novel assay involving repetitive cotyledon wounding in Arabidopsis seedlings, we uncovered a function of JA in suppressing cell division and elongation in roots. Regulatory JA signalling components were then manipulated to delineate their relative impacts on root growth. The new transcription factor mutant myc2-322B was isolated. In vitro transcription assays and whole-plant approaches revealed that myc2-322B is a dosage-dependent gain-of-function mutant that can amplify JA growth responses. Moreover, myc2-322B displayed extreme hypersensitivity to JA that totally suppressed root elongation. The mutation weakly reduced root growth in undamaged plants but, when the upstream negative regulator NINJA was genetically removed, myc2-322B powerfully repressed root growth through its effects on cell division and cell elongation. Furthermore, in a JA-deficient mutant background, ninja1 myc2-322B still repressed root elongation, indicating that it is possible to generate JA-responses in the absence of JA. We show that NINJA forms a broadly expressed regulatory layer that is required to inhibit JA signalling in the apex of roots grown under basal conditions. By contrast, MYC2, MYC3 and MYC4 displayed cell layer-specific localisations and MYC3 and MYC4 were expressed in mutually exclusive regions. In nature, growing roots are likely subjected to constant mechanical stress during soil penetration that could lead to JA production and subsequent detrimental effects on growth. Our data reveal how distinct negative regulatory layers, including both NINJA-dependent and -independent mechanisms, restrain JA responses to allow normal root growth. Mechanistic insights from this work underline the importance of mapping JA signalling components to specific

Host perception of jasmonates promotes infection by Fusarium oxysporum formae speciales that produce isoleucine- and leucine-conjugated jasmonates

PubMed Central

Cole, Stephanie J.; Yoon, Alexander J.; Faull, Kym F.; Diener, Andrew C.

2014-01-01

Summary Three pathogenic forms, or formae speciales, of Fusarium oxysporum infect the roots of Arabidopsis thaliana belowground, instigating symptoms of wilt disease in leaves aboveground. In prior reports, Arabidopsis mutants that are deficient in the biosynthesis of abscisic acid or salicylic acid or insensitive to ethylene or jasmonates exhibit more or less wilt disease than wild type, implicating the involvement of hormones in the normal host response to F. oxysporum. Our analysis of hormone-related mutants finds no evidence that endogenous hormones contribute to infection in roots. Mutants that are deficient in abscisic acid and insensitive to ethylene have no less infection than wild type, though they exhibit less disease. Whether a mutant that is insensitive to jasmonates affects infection depends on which forma specialis is infecting roots. Insensitivity to jasmonates suppresses infection by F. oxysporum forma specialis conglutinans and F. oxysporum forma specialis matthioli, which produce isoleucine- and leucine-conjugated jasmonate (JA-Ile/Leu) in culture filtrates; whereas, insensitivity to jasmonates has no effect on infection by F. oxysporum forma specialis raphani, which produces no detectable JA-Ile/Leu. Furthermore, insensitivity to jasmonates has no effect on wilt disease of tomato, and the tomato pathogen F. oxysporum forma specialis lycopersici produces no detectable jasmonates. Thus, some but not all F. oxysporum pathogens appear to utilize jasmonates as effectors, promoting infection in roots and/or development of symptoms in shoots. Only when infection of roots is promoted by jasmonates is wilt disease enhanced in a mutant deficient in salicylic acid biosynthesis. PMID:24387225
Response of tobacco to the Pseudomonas syringae pv. Tomato DC3000 is mainly dependent on salicylic acid signaling pathway.

PubMed

Liu, Yang; Wang, Li; Cai, Guohua; Jiang, Shanshan; Sun, Liping; Li, Dequan

2013-07-01

Pseudomonas syringae pv. Tomato DC3000 (Pst DC3000) was the first pathogen to be demonstrated to infect Arabidopsis and to cause disease symptoms in the laboratory setting. However, the defense response to Pst DC3000 was unclear in tobacco. In this report, the expression profiles of twelve defense response-related genes were analyzed after treatment with salicylic acid (SA), jasmonic acid (JA), and pathogen Pst DC3000 by qRT-PCR. According to our results, it could be presented that the genes primarily induced by SA were also induced to higher levels after Pst DC3000 infection. SA accumulation could be induced to a higher level than that of JA after Pst DC3000 infection. In addition, SA could result in hypersensitive response (HR), which did not completely depend on accumulation of reactive oxygen species. These results indicated that tobacco mainly depended on SA signaling pathway rather than on JA signaling pathway in response to Pst DC3000. Further study demonstrated that JA could significantly inhibit the accumulation of SA and the generation of the HR induced by Pst DC3000. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.
Arabidopsis histone methyltransferase SET DOMAIN GROUP8 mediates induction of the jasmonate/ethylene pathway genes in plant defense response to necrotrophic fungi.

PubMed

Berr, Alexandre; McCallum, Emily J; Alioua, Abdelmalek; Heintz, Dimitri; Heitz, Thierry; Shen, Wen-Hui

2010-11-01

As sessile organisms, plants have to endure a wide variety of biotic and abiotic stresses, and accordingly they have evolved intricate and rapidly inducible defense strategies associated with the activation of a battery of genes. Among other mechanisms, changes in chromatin structure are thought to provide a flexible, global, and stable means for the regulation of gene transcription. In support of this idea, we demonstrate here that the Arabidopsis (Arabidopsis thaliana) histone methyltransferase SET DOMAIN GROUP8 (SDG8) plays a crucial role in plant defense against fungal pathogens by regulating a subset of genes within the jasmonic acid (JA) and/or ethylene signaling pathway. We show that the loss-of-function mutant sdg8-1 displays reduced resistance to the necrotrophic fungal pathogens Alternaria brassicicola and Botrytis cinerea. While levels of JA, a primary phytohormone involved in plant defense, and camalexin, a major phytoalexin against fungal pathogens, remain unchanged or even above normal in sdg8-1, induction of several defense genes within the JA/ethylene signaling pathway is severely compromised in response to fungal infection or JA treatment in mutant plants. Both downstream genes and, remarkably, also upstream mitogen-activated protein kinase kinase genes MKK3 and MKK5 are misregulated in sdg8-1. Accordingly, chromatin immunoprecipitation analysis shows that sdg8-1 impairs dynamic changes of histone H3 lysine 36 methylation at defense marker genes as well as at MKK3 and MKK5, which normally occurs upon infection with fungal pathogens or methyl JA treatment in wild-type plants. Our data indicate that SDG8-mediated histone H3 lysine 36 methylation may serve as a memory of permissive transcription for a subset of defense genes, allowing rapid establishment of transcriptional induction.
Modularized Smad-regulated TGFβ signaling pathway.

PubMed

Li, Yongfeng; Wang, Minli; Carra, Claudio; Cucinotta, Francis A

2012-12-01

The transforming Growth Factor β (TGFβ) signaling pathway is a prominent regulatory signaling pathway controlling various important cellular processes. TGFβ signaling can be induced by several factors including ionizing radiation. The pathway is regulated in a negative feedback loop through promoting the nuclear import of the regulatory Smads and a subsequent expression of inhibitory Smad7, that forms ubiquitin ligase with Smurf2, targeting active TGFβ receptors for degradation. In this work, we proposed a mathematical model to study the Smad-regulated TGFβ signaling pathway. By modularization, we are able to analyze mathematically each component subsystem and recover the nonlinear dynamics of the entire network system. Meanwhile the excitability, a common feature observed in the biological systems, in the TGFβ signaling pathway is discussed and supported as well by numerical simulation, indicating the robustness of the model. Published by Elsevier Inc.
Host perception of jasmonates promotes infection by Fusarium oxysporum formae speciales that produce isoleucine- and leucine-conjugated jasmonates.

PubMed

Cole, Stephanie J; Yoon, Alexander J; Faull, Kym F; Diener, Andrew C

2014-08-01

Three pathogenic forms, or formae speciales (f. spp.), of Fusarium oxysporum infect the roots of Arabidopsis thaliana below ground, instigating symptoms of wilt disease in leaves above ground. In previous reports, Arabidopsis mutants that are deficient in the biosynthesis of abscisic acid or salicylic acid or insensitive to ethylene or jasmonates exhibited either more or less wilt disease, than the wild-type, implicating the involvement of hormones in the normal host response to F. oxysporum. Our analysis of hormone-related mutants finds no evidence that endogenous hormones contribute to infection in roots. Mutants that are deficient in abscisic acid and insensitive to ethylene show no less infection than the wild-type, although they exhibit less disease. Whether a mutant that is insensitive to jasmonates affects infection depends on which forma specialis (f. sp.) is infecting the roots. Insensitivity to jasmonates suppresses infection by F. oxysporum f. sp. conglutinans and F. oxysporum f. sp. matthioli, which produce isoleucine- and leucine-conjugated jasmonate (JA-Ile/Leu), respectively, in culture filtrates, whereas insensitivity to jasmonates has no effect on infection by F. oxysporum f. sp. raphani, which produces no detectable JA-Ile/Leu. Furthermore, insensitivity to jasmonates has no effect on wilt disease of tomato, and the tomato pathogen F. oxysporum f. sp. lycopersici produces no detectable jasmonates. Thus, some, but not all, F. oxysporum pathogens appear to utilize jasmonates as effectors, promoting infection in roots and/or the development of symptoms in shoots. Only when the infection of roots is promoted by jasmonates is wilt disease enhanced in a mutant deficient in salicylic acid biosynthesis. © 2014 BSPP AND JOHN WILEY & SONS LTD.
Defense Priming and Jasmonates: A Role for Free Fatty Acids in Insect Elicitor-Induced Long Distance Signaling

PubMed Central

Li, Ting; Cofer, Tristan; Engelberth, Marie; Engelberth, Jurgen

2016-01-01

Green leaf volatiles (GLV) prime plants against insect herbivore attack resulting in stronger and faster signaling by jasmonic acid (JA). In maize this response is specifically linked to insect elicitor (IE)-induced signaling processes, which cause JA accumulation not only around the damage site, but also in distant tissues, presumably through the activation of electrical signals. Here, we present additional data further characterizing these distal signaling events in maize. Also, we describe how exposure to GLV increases free fatty acid (fFA) levels in maize seedlings, but also in other plants, and how increased fFA levels affect IE-induced JA accumulation. Increased fFA, in particular α-linolenic acid (LnA), caused a significant increase in JA accumulation after IE treatment, while JA induced by mechanical wounding (MW) alone was not affected. We also identified treatments that significantly decreased certain fFA level including simulated wind and rain. In such treated plants, IE-induced JA accumulation was significantly reduced when compared to un-moved control plants, while MW-induced JA accumulation was not significantly affected. Since only IE-induced JA accumulation was altered by changes in the fFA composition, we conclude that changing levels of fFA affect primarily IE-induced signaling processes rather than serving as a substrate for JA. PMID:27135225
Resistance to Hemi-Biotrophic F. graminearum Infection Is Associated with Coordinated and Ordered Expression of Diverse Defense Signaling Pathways

PubMed Central

Yi, Hongying; Yang, Liming; Kong, Zhongxin; Zhang, Lixia; Xue, Shulin; Jia, Haiyan; Ma, Zhengqiang

2011-01-01

Fusarium species cause serious diseases in cereal staple food crops such as wheat and maize. Currently, the mechanisms underlying resistance to Fusarium-caused diseases are still largely unknown. In the present study, we employed a combined proteomic and transcriptomic approach to investigate wheat genes responding to F. graminearum infection that causes Fusarium head blight (FHB). We found a total of 163 genes and 37 proteins that were induced by infection. These genes and proteins were associated with signaling pathways mediated by salicylic acid (SA), jasmonic acid (JA), ethylene (ET), calcium ions, phosphatidic acid (PA), as well as with reactive oxygen species (ROS) production and scavenging, antimicrobial compound synthesis, detoxification, and cell wall fortification. We compared the time-course expression profiles between FHB-resistant Wangshuibai plants and susceptible Meh0106 mutant plants of a selected set of genes that are critical to the plants' resistance and defense reactions. A biphasic phenomenon was observed during the first 24 h after inoculation (hai) in the resistant plants. The SA and Ca2+ signaling pathways were activated within 6 hai followed by the JA mediated defense signaling activated around 12 hai. ET signaling was activated between these two phases. Genes for PA and ROS synthesis were induced during the SA and JA phases, respectively. The delayed activation of the SA defense pathway in the mutant was associated with its susceptibility. After F. graminearum infection, the endogenous contents of SA and JA in Wangshuibai and the mutant changed in a manner similar to the investigated genes corresponding to the individual pathways. A few genes for resistance-related cell modification and phytoalexin production were also identified. This study provided important clues for designing strategies to curb diseases caused by Fusarium. PMID:21533105
Salicylic acid receptors activate jasmonic acid signalling through a non-canonical pathway to promote effector-triggered immunity.

PubMed

Liu, Lijing; Sonbol, Fathi-Mohamed; Huot, Bethany; Gu, Yangnan; Withers, John; Mwimba, Musoki; Yao, Jian; He, Sheng Yang; Dong, Xinnian

2016-10-11

It is an apparent conundrum how plants evolved effector-triggered immunity (ETI), involving programmed cell death (PCD), as a major defence mechanism against biotrophic pathogens, because ETI-associated PCD could leave them vulnerable to necrotrophic pathogens that thrive on dead host cells. Interestingly, during ETI, the normally antagonistic defence hormones, salicylic acid (SA) and jasmonic acid (JA) associated with defence against biotrophs and necrotrophs respectively, both accumulate to high levels. In this study, we made the surprising finding that JA is a positive regulator of RPS2-mediated ETI. Early induction of JA-responsive genes and de novo JA synthesis following SA accumulation is activated through the SA receptors NPR3 and NPR4, instead of the JA receptor COI1. We provide evidence that NPR3 and NPR4 may mediate this effect by promoting degradation of the JA transcriptional repressor JAZs. This unique interplay between SA and JA offers a possible explanation of how plants can mount defence against a biotrophic pathogen without becoming vulnerable to necrotrophic pathogens.
Changes in actin dynamics are involved in salicylic acid signaling pathway.

PubMed

Matoušková, Jindřiška; Janda, Martin; Fišer, Radovan; Sašek, Vladimír; Kocourková, Daniela; Burketová, Lenka; Dušková, Jiřina; Martinec, Jan; Valentová, Olga

2014-06-01

Changes in actin cytoskeleton dynamics are one of the crucial players in many physiological as well as non-physiological processes in plant cells. Positioning of actin filament arrays is necessary for successful establishment of primary lines of defense toward pathogen attack, depolymerization leads very often to the enhanced susceptibility to the invading pathogen. On the other hand it was also shown that the disruption of actin cytoskeleton leads to the induction of defense response leading to the expression of PATHOGENESIS RELATED proteins (PR). In this study we show that pharmacological actin depolymerization leads to the specific induction of genes in salicylic acid pathway but not that involved in jasmonic acid signaling. Life imaging of leafs of Arabidopsis thaliana with GFP-tagged fimbrin (GFP-fABD2) treated with 1 mM salicylic acid revealed rapid disruption of actin filaments resembling the pattern viewed after treatment with 200 nM latrunculin B. The effect of salicylic acid on actin filament fragmentation was prevented by exogenous addition of phosphatidic acid, which binds to the capping protein and thus promotes actin polymerization. The quantitative evaluation of actin filament dynamics is also presented. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
The Akt signaling pathway

PubMed Central

Madhunapantula, SubbaRao V; Mosca, Paul J

2011-01-01

Studies using cultured melanoma cells and patient tumor biopsies have demonstrated deregulated PI3 kinase-Akt3 pathway activity in ∼70% of melanomas. Furthermore, targeting Akt3 and downstream PRAS40 has been shown to inhibit melanoma tumor development in mice. Although these preclinical studies and several other reports using small interfering RNAs and pharmacological agents targeting key members of this pathway have been shown to retard melanoma development, analysis of early Phase I and Phase II clinical trials using pharmacological agents to target this pathway demonstrate the need for (1) selection of patients whose tumors have PI3 kinase-Akt pathway deregulation, (2) further optimization of therapeutic agents for increased potency and reduced toxicity, (3) the identification of additional targets in the same pathway or in other signaling cascades that synergistically inhibit the growth and progression of melanoma, and (4) better methods for targeted delivery of pharmaceutical agents inhibiting this pathway. In this review we discuss key potential targets in PI3K-Akt3 signaling, the status of pharmacological agents targeting these proteins, drugs under clinical development, and strategies to improve the efficacy of therapeutic agents targeting this pathway. PMID:22157148
The canonical Wnt signaling pathway in autism.

PubMed

Zhang, Yinghua; Yuan, Xiangshan; Wang, Zhongping; Li, Ruixi

2014-01-01

Mounting attention is being focused on the canonical Wnt signaling pathway which has been implicated in the pathogenesis of autism in some our and other recent studies. The canonical Wnt pathway is involved in cell proliferation, differentiation and migration, especially during nervous system development. Given its various functions, dysfunction of the canonical Wnt pathway may exert adverse effects on neurodevelopment and therefore leads to the pathogenesis of autism. Here, we review human and animal studies that implicate the canonical Wnt signal transduction pathway in the pathogenesis of autism. We also describe the crosstalk between the canonical Wnt pathway and the Notch signaling pathway in several types of autism spectrum disorders, including Asperger syndrome and Fragile X. Further research on the crosstalk between the canonical Wnt signaling pathway and other signaling cascades in autism may be an efficient avenue to understand the etiology of autism and ultimately lead to alternative medications for autism-like phenotypes.
Exogenous application of methyl jasmonate and salicylic acid on citrus foliage: Effecs on foliar volatiles and aggregation behavior of Asian citrus psyllid (Diaphorina citri)

USDA-ARS?s Scientific Manuscript database

Methyl jasmonate (MeJA) and salicylic acid (SA) are well-known activators of chemical defenses in plants. The SA pathway is involved in citrus response to infection by Candidatus Liberibacter asiaticus (CLas); less is known about the role of jasmonates in citrus defense response. We examined the eff...
Methyl Jasmonate-Induced Lipidomic and Biochemical Alterations in the Intertidal Macroalga Gracilaria dura (Gracilariaceae, Rhodophyta)

PubMed Central

Kumari, Puja; Reddy, C.R.K.; Jha, Bhavanath

2015-01-01

The role of exogenously added methyl jasmonate (MeJA), a lipid-derived signaling compound, in inducing oxidative stress in the marine red macroalga Gracilaria dura was investigated. MeJA at a concentration of 1–100 µM was a strong stimulant of reactive oxygen species (H2O2, HO· and O2·−) (P < 0.05) causing considerable oxidative stress in G. dura. This further led to lipid peroxidation and degradation of the pigments Chl a and phycocyanin, with a concomitant increase in phycoerythrin. The MeJA-induced oxidative burst also led to the induction of a fatty acid oxidation cascade, resulting in the synthesis of hydroxy-oxylipins and the up-regulation of the 13-lipoxygenase pathway. Electrospray ionization-mass spectrometry-based shotgun lipidomic analysis revealed that monogalactosyldiacylglycerol (a chloroplastic glycerolipid) and phosphatidylcholine (extrachloroplastidic phopholipid) were the most affected lipid classes. The degradation of 18:3-fatty acid-containing monogalactosyldiacylglycerol inferred that it provided fatty acyl chains for the biosynthesis of 13-hydroperoxylinolenic acid, which was further directed towards either the jasmonate pathway or other alternative pathways of the fatty acid oxidation cascade, analogous to higher plants. Also, G. dura modulated the lipid acyl chains in such a way that no significant change was observed in the fatty acid profile of the treated thalli as compared with those of the control, except for C16:0, C16:1 (n-9), C20:3 (n-6) and C20:4 (n-6) (P < 0.05). Furthermore, MeJA caused the accumulation of phenolic compounds and the up-regulation of enzymes involved in secondary metabolism such as polyphenol oxidase, shikimate dehydrogenase and phenylalanine ammonia-lyase, indicating a shift towards secondary metabolism as a defense strategy to combat the induced oxidative stress. PMID:26276825
Botrytis cinerea Manipulates the Antagonistic Effects between Immune Pathways to Promote Disease Development in Tomato[C][W][OA

PubMed Central

El Oirdi, Mohamed; El Rahman, Taha Abd; Rigano, Luciano; El Hadrami, Abdelbasset; Rodriguez, María Cecilia; Daayf, Fouad; Vojnov, Adrian; Bouarab, Kamal

2011-01-01

Plants have evolved sophisticated mechanisms to sense and respond to pathogen attacks. Resistance against necrotrophic pathogens generally requires the activation of the jasmonic acid (JA) signaling pathway, whereas the salicylic acid (SA) signaling pathway is mainly activated against biotrophic pathogens. SA can antagonize JA signaling and vice versa. Here, we report that the necrotrophic pathogen Botrytis cinerea exploits this antagonism as a strategy to cause disease development. We show that B. cinerea produces an exopolysaccharide, which acts as an elicitor of the SA pathway. In turn, the SA pathway antagonizes the JA signaling pathway, thereby allowing the fungus to develop its disease in tomato (Solanum lycopersicum). SA-promoted disease development occurs through Nonexpressed Pathogen Related1. We also show that the JA signaling pathway required for tomato resistance against B. cinerea is mediated by the systemin elicitor. These data highlight a new strategy used by B. cinerea to overcome the plant’s defense system and to spread within the host. PMID:21665999
Analysis of defense signals in Arabidopsis thaliana leaves by ultra-performance liquid chromatography/tandem mass spectrometry: jasmonates, salicylic acid, abscisic acid.

PubMed

Stingl, Nadja; Krischke, Markus; Fekete, Agnes; Mueller, Martin J

2013-01-01

Defense signaling compounds and phytohormones play an essential role in the regulation of plant responses to various environmental abiotic and biotic stresses. Among the most severe stresses are herbivory, pathogen infection, and drought stress. The major hormones involved in the regulation of these responses are 12-oxo-phytodienoic acid (OPDA), the pro-hormone jasmonic acid (JA) and its biologically active isoleucine conjugate (JA-Ile), salicylic acid (SA), and abscisic acid (ABA). These signaling compounds are present and biologically active at very low concentrations from ng/g to μg/g dry weight. Accurate and sensitive quantification of these signals has made a significant contribution to the understanding of plant stress responses. Ultra-performance liquid chromatography (UPLC) coupled with a tandem quadrupole mass spectrometer (MS/MS) has become an essential technique for the analysis and quantification of these compounds.
MYC2 Differentially Modulates Diverse Jasmonate-Dependent Functions in Arabidopsis[W

PubMed Central

Dombrecht, Bruno; Xue, Gang Ping; Sprague, Susan J.; Kirkegaard, John A.; Ross, John J.; Reid, James B.; Fitt, Gary P.; Sewelam, Nasser; Schenk, Peer M.; Manners, John M.; Kazan, Kemal

2007-01-01

The Arabidopsis thaliana basic helix-loop-helix Leu zipper transcription factor (TF) MYC2/JIN1 differentially regulates jasmonate (JA)-responsive pathogen defense (e.g., PDF1.2) and wound response (e.g., VSP) genes. In this study, genome-wide transcriptional profiling of wild type and mutant myc2/jin1 plants followed by functional analyses has revealed new roles for MYC2 in the modulation of diverse JA functions. We found that MYC2 negatively regulates Trp and Trp-derived secondary metabolism such as indole glucosinolate biosynthesis during JA signaling. Furthermore, MYC2 positively regulates JA-mediated resistance to insect pests, such as Helicoverpa armigera, and tolerance to oxidative stress, possibly via enhanced ascorbate redox cycling and flavonoid biosynthesis. Analyses of MYC2 cis binding elements and expression of MYC2-regulated genes in T-DNA insertion lines of a subset of MYC2–regulated TFs suggested that MYC2 might modulate JA responses via differential regulation of an intermediate spectrum of TFs with activating or repressing roles in JA signaling. MYC2 also negatively regulates its own expression, and this may be one of the mechanisms used in fine-tuning JA signaling. Overall, these results provide new insights into the function of MYC2 and the transcriptional coordination of the JA signaling pathway. PMID:17616737
Different mechanisms of Trichoderma virens-mediated resistance in tomato against Fusarium wilt involve the jasmonic and salicylic acid pathways.

PubMed

Jogaiah, Sudisha; Abdelrahman, Mostafa; Tran, Lam-Son Phan; Ito, Shin-Ichi

2018-04-01

In the present study, we investigated the role of Trichoderma virens (TriV_JSB100) spores or cell-free culture filtrate in the regulation of growth and activation of the defence responses of tomato (Solanum lycopersicum) plants against Fusarium oxysporum f. sp. lycopersici by the development of a biocontrol-plant-pathogen interaction system. Two-week-old tomato seedlings primed with TriV_JSB100 spores cultured on barley grains (BGS) or with cell-free culture filtrate (CF) were inoculated with Fusarium pathogen under glasshouse conditions; this resulted in significantly lower disease incidence in tomato Oogata-Fukuju plants treated with BGS than in those treated with CF. To dissect the pathways associated with this response, jasmonic acid (JA) and salicylic acid (SA) signalling in BGS- and CF-induced resistance was evaluated using JA- and SA-impaired tomato lines. We observed that JA-deficient mutant def1 plants were susceptible to Fusarium pathogen when they were treated with BGS. However, wild-type (WT) BGS-treated tomato plants showed a higher JA level and significantly lower disease incidence. SA-deficient mutant NahG plants treated with CF were also found to be susceptible to Fusarium pathogen and displayed low SA levels, whereas WT CF-treated tomato plants exhibited moderately lower disease levels and substantially higher SA levels. Expression of the JA-responsive defensin gene PDF1 was induced in WT tomato plants treated with BGS, whereas the SA-inducible pathogenesis-related protein 1 acidic (PR1a) gene was up-regulated in WT tomato plants treated with CF. These results suggest that TriV_JSB100 BGS and CF differentially induce JA and SA signalling cascades for the elicitation of Fusarium oxysporum resistance in tomato. © 2017 BSPP AND JOHN WILEY & SONS LTD.
The Drosophila imd signaling pathway.

PubMed

Myllymäki, Henna; Valanne, Susanna; Rämet, Mika

2014-04-15

The fruit fly, Drosophila melanogaster, has helped us to understand how innate immunity is activated. In addition to the Toll receptor and the Toll signaling pathway, the Drosophila immune response is regulated by another evolutionarily conserved signaling cascade, the immune deficiency (Imd) pathway, which activates NF-κB. In fact, the Imd pathway controls the expression of most of the antimicrobial peptides in Drosophila; thus, it is indispensable for normal immunity in flies. In this article, we review the current literature on the Drosophila Imd pathway, with special emphasis on its role in the (patho)physiology of different organs. We discuss the systemic response, as well as local responses, in the epithelial and mucosal surfaces and the nervous system.
ERβ induces the differentiation of cultured osteoblasts by both Wnt/β-catenin signaling pathway and estrogen signaling pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yin, Xinhua; Wang, Xiaoyuan; Hu, Xiongke

Although 17β-estradial (E2) is known to stimulate bone formation, the underlying mechanisms are not fully understood. Recent studies have implicated the Wnt/β-catenin pathway as a major signaling cascade in bone biology. The interactions between Wnt/β-catenin signaling pathway and estrogen signaling pathways have been reported in many tissues. In this study, E2 significantly increased the expression of β-catenin by inducing phosphorylations of GSK3β at serine 9. ERβ siRNAs were transfected into MC3T3-E1 cells and revealed that ERβ involved E2-induced osteoblasts proliferation and differentiation via Wnt/β-catenin signaling. The osteoblast differentiation genes (BGP, ALP and OPN) and proliferation related gene (cyclin D1) expressionmore » were significantly induced by E2-mediated ERβ. Furthermore immunofluorescence and immunoprecipitation analysis demonstrated that E2 induced the accumulation of β-catenin protein in the nucleus which leads to interaction with T-cell-specific transcription factor/lymphoid enhancer binding factor (TCF/LEF) transcription factors. Taken together, these findings suggest that E2 promotes osteoblastic proliferation and differentiation by inducing proliferation-related and differentiation-related gene expression via ERβ/GSK-3β-dependent Wnt/β-catenin signaling pathway. Our findings provide novel insights into the mechanisms of action of E2 in osteoblastogenesis. - Highlights: • 17β-estradial (E2) promotes GSK3-β phosphorylation. • E2 activates the Wnt/β-catenin signaling pathway. • The Wnt/β-catenin signaling pathway interacts with estrogen signaling pathways. • E2-mediated ER induced osteoblast differentiation and proliferation related genes expression.« less
Salicylic acid signaling inhibits apoplastic reactive oxygen species signaling.

PubMed

Xu, Enjun; Brosché, Mikael

2014-06-04

Reactive oxygen species (ROS) are used by plants as signaling molecules during stress and development. Given the amount of possible challenges a plant face from their environment, plants need to activate and prioritize between potentially conflicting defense signaling pathways. Until recently, most studies on signal interactions have focused on phytohormone interaction, such as the antagonistic relationship between salicylic acid (SA)-jasmonic acid and cytokinin-auxin. In this study, we report an antagonistic interaction between SA signaling and apoplastic ROS signaling. Treatment with ozone (O3) leads to a ROS burst in the apoplast and induces extensive changes in gene expression and elevation of defense hormones. However, Arabidopsis thaliana dnd1 (defense no death1) exhibited an attenuated response to O3. In addition, the dnd1 mutant displayed constitutive expression of defense genes and spontaneous cell death. To determine the exact process which blocks the apoplastic ROS signaling, double and triple mutants involved in various signaling pathway were generated in dnd1 background. Simultaneous elimination of SA-dependent and SA-independent signaling components from dnd1 restored its responsiveness to O3. Conversely, pre-treatment of plants with SA or using mutants that constitutively activate SA signaling led to an attenuation of changes in gene expression elicited by O3. Based upon these findings, we conclude that plants are able to prioritize the response between ROS and SA via an antagonistic action of SA and SA signaling on apoplastic ROS signaling.

Salicylic acid signaling inhibits apoplastic reactive oxygen species signaling

PubMed Central

2014-01-01

Background Reactive oxygen species (ROS) are used by plants as signaling molecules during stress and development. Given the amount of possible challenges a plant face from their environment, plants need to activate and prioritize between potentially conflicting defense signaling pathways. Until recently, most studies on signal interactions have focused on phytohormone interaction, such as the antagonistic relationship between salicylic acid (SA)-jasmonic acid and cytokinin-auxin. Results In this study, we report an antagonistic interaction between SA signaling and apoplastic ROS signaling. Treatment with ozone (O3) leads to a ROS burst in the apoplast and induces extensive changes in gene expression and elevation of defense hormones. However, Arabidopsis thaliana dnd1 (defense no death1) exhibited an attenuated response to O3. In addition, the dnd1 mutant displayed constitutive expression of defense genes and spontaneous cell death. To determine the exact process which blocks the apoplastic ROS signaling, double and triple mutants involved in various signaling pathway were generated in dnd1 background. Simultaneous elimination of SA-dependent and SA-independent signaling components from dnd1 restored its responsiveness to O3. Conversely, pre-treatment of plants with SA or using mutants that constitutively activate SA signaling led to an attenuation of changes in gene expression elicited by O3. Conclusions Based upon these findings, we conclude that plants are able to prioritize the response between ROS and SA via an antagonistic action of SA and SA signaling on apoplastic ROS signaling. PMID:24898702
A calmodulin-binding/CGCG box DNA-binding protein family involved in multiple signaling pathways in plants

NASA Technical Reports Server (NTRS)

Yang, Tianbao; Poovaiah, B. W.

2002-01-01

We reported earlier that the tobacco early ethylene-responsive gene NtER1 encodes a calmodulin-binding protein (Yang, T., and Poovaiah, B. W. (2000) J. Biol. Chem. 275, 38467-38473). Here we demonstrate that there is one NtER1 homolog as well as five related genes in Arabidopsis. These six genes are rapidly and differentially induced by environmental signals such as temperature extremes, UVB, salt, and wounding; hormones such as ethylene and abscisic acid; and signal molecules such as methyl jasmonate, H(2)O(2), and salicylic acid. Hence, they were designated as AtSR1-6 (Arabidopsis thaliana signal-responsive genes). Ca(2+)/calmodulin binds to all AtSRs, and their calmodulin-binding regions are located on a conserved basic amphiphilic alpha-helical motif in the C terminus. AtSR1 targets the nucleus and specifically recognizes a novel 6-bp CGCG box (A/C/G)CGCG(G/T/C). The multiple CGCG cis-elements are found in promoters of genes such as those involved in ethylene signaling, abscisic acid signaling, and light signal perception. The DNA-binding domain in AtSR1 is located on the N-terminal 146 bp where all AtSR1-related proteins share high similarity but have no similarity to other known DNA-binding proteins. The calmodulin-binding nuclear proteins isolated from wounded leaves exhibit specific CGCG box DNA binding activities. These results suggest that the AtSR gene family encodes a family of calmodulin-binding/DNA-binding proteins involved in multiple signal transduction pathways in plants.
Ultrasensitive determination of jasmonic acid in plant tissues using high-performance liquid chromatography with fluorescence detection.

PubMed

Xiong, Xu-Jie; Rao, Wan-Bing; Guo, Xiao-Feng; Wang, Hong; Zhang, Hua-Shan

2012-05-23

An ultrasensitive and selective high-performance liquid chromatographic method for the volatile signaling hormone, jasmonic acid, has been developed based on precolumn derivatization with 1,3,5,7-tetramethyl-8-aminozide-difluoroboradiaza-s-indacene (BODIPY-aminozide). The derivatization reaction was carried out at 60 °C for 30 min in the presence of phosphoric acid. The formed jasmonic acid derivative was eluted using a mobile phase of methanol/pH 6.50 ammonium formate buffer/tetrahydrofuran (67:30:3, v/v/v) in 10 min on a C(18) column and detected with fluorescence detection at excitation and emission wavelengths of 495 and 505 nm, respectively. The detection limit (signal-to-noise ratio = 4) reached 1.14 × 10(-10) M or 2.29 fmol per injection (20 μL), which is the lowest of the existing methods. The proposed method has been successfully applied to the direct determination of trace jasmonic acid in the crude extracts of soybean leaves from soybean mosaic virus-infected and normal plants with recoveries of 95-104%.
Discovering causal signaling pathways through gene-expression patterns

PubMed Central

Parikh, Jignesh R.; Klinger, Bertram; Xia, Yu; Marto, Jarrod A.; Blüthgen, Nils

2010-01-01

High-throughput gene-expression studies result in lists of differentially expressed genes. Most current meta-analyses of these gene lists include searching for significant membership of the translated proteins in various signaling pathways. However, such membership enrichment algorithms do not provide insight into which pathways caused the genes to be differentially expressed in the first place. Here, we present an intuitive approach for discovering upstream signaling pathways responsible for regulating these differentially expressed genes. We identify consistently regulated signature genes specific for signal transduction pathways from a panel of single-pathway perturbation experiments. An algorithm that detects overrepresentation of these signature genes in a gene group of interest is used to infer the signaling pathway responsible for regulation. We expose our novel resource and algorithm through a web server called SPEED: Signaling Pathway Enrichment using Experimental Data sets. SPEED can be freely accessed at http://speed.sys-bio.net/. PMID:20494976
Low concentrations of salicylic acid delay methyl jasmonate-induced leaf senescence by up-regulating nitric oxide synthase activity.

PubMed

Ji, Yingbin; Liu, Jian; Xing, Da

2016-09-01

In plants, extensive efforts have been devoted to understanding the crosstalk between salicylic acid (SA) and jasmonic acid (JA) signaling in pathogen defenses, but this crosstalk has scarcely been addressed during senescence. In this study, the effect of SA application on methyl jasmonate (MeJA)-induced leaf senescence was assessed. We found that low concentrations of SA (1-50 μM) played a delayed role against the senescence promoted by MeJA. Furthermore, low concentrations of SA enhanced plant antioxidant defenses and restricted reactive oxygen species (ROS) accumulation in MeJA-treated leaves. When applied simultaneously with MeJA, low concentrations of SA triggered a nitric oxide (NO) burst, and the elevated NO levels were linked to the nitric oxide associated 1 (NOA1)-dependent pathway via nitric oxide synthase (NOS) activity. The ability of SA to up-regulate plant antioxidant defenses, reduce ROS accumulation, and suppress leaf senescence was lost in NO-deficient Atnoa1 plants. In a converse manner, exogenous addition of NO donors increased the plant antioxidant capacity and lowered the ROS levels in MeJA-treated leaves. Taken together, the results indicate that SA at low concentrations counteracts MeJA-induced leaf senescence through NOA1-dependent NO signaling and strengthening of the antioxidant defense. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Hedgehog signaling pathway in neuroblastoma differentiation.

PubMed

Souzaki, Ryota; Tajiri, Tatsuro; Souzaki, Masae; Kinoshita, Yoshiaki; Tanaka, Sakura; Kohashi, Kenichi; Oda, Yoshinao; Katano, Mitsuo; Taguchi, Tomoaki

2010-12-01

The hedgehog (Hh) signaling pathway is activated in some adult cancers. On the other hand, the Hh signaling pathway plays an important role in the development of the neural crest in embryos. The aim of this study is to show the activation of Hh signaling pathway in neuroblastoma (NB), a pediatric malignancy arising from neural crest cells, and to reveal the meaning of the Hh signaling pathway in NB development. This study analyzed the expression of Sonic hedgehog (Shh), GLI1, and Patched 1 (Ptch1), transactivators of Hh signaling pathway, by immunohistochemistry in 82 NB and 10 ganglioneuroblastoma cases. All 92 cases were evaluated for the status of MYCN amplification. Of the 92 cases, 67 (73%) were positive for Shh, 62 cases (67%) were positive for GLI1, and 73 cases (79%) were positive for Ptch1. Only 2 (10%) of the 20 cases with MYCN amplification were positive for Shh and GLI1, and 4 cases (20%) were positive for Ptch1 (MYCN amplification vs no MYCN amplification, P ≦ .01). The percentage of GLI1-positive cells in the cases with INSS stage 1 without MYCN amplification was significantly higher than that with INSS stage 4. Of 72 cases without MYCN amplification, 60 were GLI1-positive. Twelve cases were GLI1-negative, and the prognosis of the GLI1-positive cases was significantly better than that of the GLI1-negative cases (P = .015). Most of NBs without MYCN amplification were positive for Shh, GLI1, and Ptch1. In the cases without MYCN amplification, the high expression of GLI1 was significantly associated with early clinical stage and a good prognosis of the patients. In contrast to adult cancers, the activation of the Hh signaling pathway in NB may be associated with the differentiation of the NB. Copyright © 2010 Elsevier Inc. All rights reserved.
Oligogalacturonide-mediated induction of a gene involved in jasmonic acid synthesis in response to the cell-wall-degrading enzymes of the plant pathogen Erwinia carotovora.

PubMed

Norman, C; Vidal, S; Palva, E T

1999-07-01

Identification of Arabidopsis thaliana genes responsive to plant cell-wall-degrading enzymes of Erwinia carotovora subsp. carotovora led to the isolation of a cDNA clone with high sequence homology to the gene for allene oxide synthase, an enzyme involved in the biosynthesis of jasmonates. Expression of the corresponding gene was induced by the extracellular enzymes from this pathogen as well as by treatment with methyl jasmonate and short oligogalacturonides (OGAs). This suggests that OGAs are involved in the induction of the jasmonate pathway during plant defense response to E. carotovora subsp. carotovora attack.
Analysis of two potential long-distance signaling molecules, LjCLE-RS1/2 and jasmonic acid, in a hypernodulating mutant too much love.

PubMed

Magori, Shimpei; Kawaguchi, Masayoshi

2010-04-01

Legume plants tightly control the number and development of root nodules. This is partly regulated by a long-distance signaling known as auto-regulation of nodulation (AON). AON signaling involves at least two potential long-distance signals: root-derived signal and shoot-derived signal. However, their molecular characteristics and the mode of action remain unclear. In our recent study, we isolated a novel Lotus japonicus hypernodulating mutant too much love (tml). Based on several grafting experiments, we concluded that its causative gene TML functions as a receptor of the shoot-derived signal. This finding prompted us to ask how the candidates of the long-distance signal molecules, LjCLE-RS1/2 and jasmonic acid (JA), are affected in tml mutants. Expression analysis revealed that rapid induction of LjCLE-RS1/2 upon rhizobial inoculation is still intact in tml, supporting that TML plays a role in reception of the shoot-derived signal but not in generation of the root-derived signal. Furthermore, physiological analysis showed that JA, a candidate of the shoot-derived signal, can suppress tml hypernodulation. Therefore, contrary to the previous report, JA might not be a component of AON signaling.
Cell Signaling Pathways that Regulate Ag Presentation

PubMed Central

Brutkiewicz, Randy R.

2016-01-01

Cell signaling pathways regulate much in the life of a cell: from shuttling cargo through intracellular compartments and onto the cell surface, how it should respond to stress, protecting itself from harm (environmental insults or infections), to ultimately, death by apoptosis. These signaling pathways are important for various aspects of the immune response as well. However, not much is known in terms of the participation of cell signaling pathways in Ag presentation--a necessary first step in the activation of innate and adaptive T cells. In this brief review, I will discuss the known signaling molecules (and pathways) that regulate how Ags are presented to T cells and the mechanism(s) if identified. Studies in this area have important implications in vaccine development and new treatment paradigms against infectious diseases, autoimmunity and cancer. PMID:27824592
Clinical implications of hedgehog signaling pathway inhibitors

PubMed Central

Liu, Hailan; Gu, Dongsheng; Xie, Jingwu

2011-01-01

Hedgehog was first described in Drosophila melanogaster by the Nobel laureates Eric Wieschaus and Christiane Nüsslein-Volhard. The hedgehog (Hh) pathway is a major regulator of cell differentiation, proliferation, tissue polarity, stem cell maintenance, and Carcinogenesis. The first link of Hh signaling to cancer was established through studies of a rare familial disease, Gorlin syndrome, in 1996. Follow-up studies revealed activation of this pathway in basal cell carcinoma, medulloblastoma and, leukemia as well as in gastrointestinal, lung, ovarian, breast, and prostate cancer. Targeted inhibition of Hh signaling is now believed to be effective in the treatment and prevention of human cancer. The discovery and synthesis of specific inhibitors for this pathway are even more exciting. In this review, we summarize major advances in the understanding of Hh signaling pathway activation in human cancer, mouse models for studying Hh-mediated Carcinogenesis, the roles of Hh signaling in tumor development and metastasis, antagonists for Hh signaling and their clinical implications. PMID:21192841
Jasmonates are essential factors inducing gummosis in tulips: mode of action of jasmonates focusing on sugar metabolism.

PubMed

Skrzypek, Edyta; Miyamoto, Kensuke; Saniewski, Marian; Ueda, Junichi

2005-05-01

The purpose of this study was to know the mechanism of jasmonates to induce gummosis in tulip (Tulipa gesneriana L. cv. Apeldoorn) shoots, especially on the focus of sugar metabolism. Gummosis in the first internode of tulip plants was induced by the application of methyl jasmonate (JA-Me, 1% w/w in lanolin) and jasmonic acid (JA, 1% w/w in lanolin) 5 days after application and strongly stimulated by the simultaneous application of ethylene-releasing compound, ethephon (2-chloroethylphosphonic acid, 1% w/w in lanolin), although ethephon alone had little effect. JA-Me stimulated ethylene production of the first internodes of tulips, ethylene production increasing up to more than 5 times at day 1 and day 3 after the application. On the other hand, application of ethephon did not increase endogenous levels of jasmonates in tulip stems. Analysis of composition of tulip gums revealed that they were consisted of glucuronoarabinoxylan with an average molecular weight of ca. 700 kDa. JA-Me strongly decreased the total amount of soluble sugars in tulip stems even in 1 day after application, being ca. 50% of initial values 5 days after application, but ethephon did not. However, both JA-Me and ethephon had almost no effect on the neutral sugar compositions of soluble sugars mainly consisting of glucose, mannose and xylose in ratio of 20:2:1 and traces of arabinose. Both JA-Me and ethephon applied exogenously stimulated senescence of tulip shoots shown by the loss of chlorophyll. These results strongly suggest that the essential factor of gummosis in tulips is jasmonates affecting the sugar metabolism in tulip shoots. The mode of action of jasmonates to induce gummosis of tulip shoots is discussed in relation to ethylene production, sugar metabolism and senescence.
Molecular mechanisms of the mammalian Hippo signaling pathway.

PubMed

Ji, Xin-yan; Zhong, Guoxuan; Zhao, Bin

2017-07-20

The Hippo pathway plays an evolutionarily conserved fundamental role in controlling organ size in multicellular organisms. Importantly, evidence from studies of patient samples and mouse models clearly indicates that deregulation of the Hippo signaling pathway plays a crucial role in the initiation and progression of many different types of human cancers. The Hippo signaling pathway is regulated by various stimuli, such as mechanical stress, G-protein coupled receptor signaling, and cellular energy status. When activated, the Hippo kinase cascade phosphorylates and inhibits the transcription co-activator YAP (Yes-associated protein), and its paralog TAZ (transcriptional coactivator with PDZ-binding motif), resulting in their cytoplasmic retention and degradation. When the Hippo signaling pathway is inactive, dephosphorylated YAP/TAZ translocate into the nucleus and activate gene transcription through binding to TEAD (TEA domain) family and other transcription factors. Such changes in gene expression promote cell proliferation and stem cell/progenitor cell self-renewal but inhibit apoptosis, thereby coordinately promote increase in organ size, tissue regeneration, and tumorigenesis. In this review, we summarize the molecular mechanisms of the mammalian Hippo signaling pathway with special emphasis on the Hippo kinase cascade and its upstream signals, the Hippo signaling pathway regulation of YAP and the mechanisms of YAP in regulation of gene transcription.
Hippo signaling pathway in cardiovascular development and diseases.

PubMed

Wang, Yong-yu; Yu, Wei; Zhou, Bin

2017-07-20

Cardiovascular diseases have become the leading cause of death in the world. Understanding the development of cardiovascular system and the pathogenesis of cardiovascular diseases will promote the generation of novel preventive and therapeutic strategy. The Hippo pathway is a recently identified signaling cascade that plays a critical role in organ size control, cell proliferation, apoptosis and fate determination of stem cells. Gene knockout and transgenic mouse models have revealed that the Hippo signaling pathway is involved in heart development, cardiomyocyte proliferation, apoptosis, hypertrophy and cardiac regeneration. The Hippo signaling pathway also regulates vascular development, differentiation and various functions of vascular cells. Dysregulation of the Hippo signaling pathway leads to different kinds of cardiovascular diseases, such as myocardial infarction, cardiac hypertrophy, neointima formation and atherosclerosis. In this review, we briefly summarize current research on the roles and regulation mechanisms of the Hippo signaling pathway in cardiovascular development and diseases.
The Fibroblast Growth Factor signaling pathway

PubMed Central

Ornitz, David M; Itoh, Nobuyuki

2015-01-01

The signaling component of the mammalian Fibroblast Growth Factor (FGF) family is comprised of eighteen secreted proteins that interact with four signaling tyrosine kinase FGF receptors (FGFRs). Interaction of FGF ligands with their signaling receptors is regulated by protein or proteoglycan cofactors and by extracellular binding proteins. Activated FGFRs phosphorylate specific tyrosine residues that mediate interaction with cytosolic adaptor proteins and the RAS-MAPK, PI3K-AKT, PLCγ, and STAT intracellular signaling pathways. Four structurally related intracellular non-signaling FGFs interact with and regulate the family of voltage gated sodium channels. Members of the FGF family function in the earliest stages of embryonic development and during organogenesis to maintain progenitor cells and mediate their growth, differentiation, survival, and patterning. FGFs also have roles in adult tissues where they mediate metabolic functions, tissue repair, and regeneration, often by reactivating developmental signaling pathways. Consistent with the presence of FGFs in almost all tissues and organs, aberrant activity of the pathway is associated with developmental defects that disrupt organogenesis, impair the response to injury, and result in metabolic disorders, and cancer. © 2015 Wiley Periodicals, Inc. PMID:25772309
Thiol-based Redox Proteins in Brassica napus Guard Cell Abscisic Acid and Methyl Jasmonate Signaling

PubMed Central

Zhu, Mengmeng; Zhu, Ning; Song, Wen-yuan; Harmon, Alice C.; Assmann, Sarah M.; Chen, Sixue

2014-01-01

SUMMARY Reversibly oxidized cysteine sulfhydryl groups serve as redox sensors or targets of redox sensing that are important in different physiological processes. Little is known, however, about redox sensitive proteins in guard cells and how they function in stomatal signaling. In this study, Brassica napus guard cell proteins altered by redox in response to abscisic acid (ABA) or methyl jasmonate (MeJA) were identified by complementary proteomics approaches, saturation differential in-gel electrophoresis (DIGE) and isotope-coded affinity tag (ICAT). In total, 65 and 118 potential redox responsive proteins were identified in ABA and MeJA treated guard cells, respectively. All the proteins contain at least one cysteine, and over half of them are predicted to form intra-molecular disulfide bonds. Most of the proteins fall into the functional groups of energy, stress and defense, and metabolism. Based on the peptide sequences identified by mass spectrometry, 30 proteins were common to ABA and MeJA treated samples. A total of 44 cysteines was mapped in all the identified proteins, and their levels of redox sensitivity were quantified. Two of the proteins, a SNRK2 kinase and an isopropylmalate dehydrogenase were confirmed to be redox regulated and involved in stomatal movement. This study creates an inventory of potential redox switches, and highlights a protein redox regulatory mechanism in guard cell ABA and MeJA signal transduction. PMID:24580573
Identification of Mild Freezing Shock Response Pathways in Barley Based on Transcriptome Profiling.

PubMed

Wang, Xiaolei; Wu, Dezhi; Yang, Qian; Zeng, Jianbin; Jin, Gulei; Chen, Zhong-Hua; Zhang, Guoping; Dai, Fei

2016-01-01

Low temperature is a major abiotic stress affecting crop growth and productivity. A better understanding of low temperature tolerance mechanisms is imperative for developing the crop cultivars with improved tolerance. We herein performed an Illumina RNA-sequencing experiment using two barley genotypes differing in freezing tolerance (Nure, tolerant and Tremois, sensitive), to determine the transcriptome profiling and genotypic difference under mild freezing shock treatment after a very short acclimation for gene induction. A total of 6474 differentially expressed genes, almost evenly distributed on the seven chromosomes, were identified. The key DEGs could be classified into six signaling pathways, i.e., Ca(2+) signaling, PtdOH signaling, CBFs pathway, ABA pathway, jasmonate pathway, and amylohydrolysis pathway. Expression values of DEGs in multiple signaling pathways were analyzed and a hypothetical model of mild freezing shock tolerance mechanism was proposed. Expression and sequence profile of HvCBFs cluster within Frost resistance-H2, a major quantitative trait locus on 5H being closely related to low temperature tolerance in barley, were further illustrated, considering the crucial role of HvCBFs on freezing tolerance. It may be concluded that multiple signaling pathways are activated in concert when barley is exposed to mild freezing shock. The pathway network we presented may provide a platform for further exploring the functions of genes involved in low temperature tolerance in barley.
Synthesis, metabolism and systemic transport of a fluorinated mimic of the endogenous jasmonate precursor OPC-8:0.

PubMed

Jimenez-Aleman, Guillermo H; Scholz, Sandra S; Heyer, Monika; Reichelt, Michael; Mithöfer, Axel; Boland, Wilhelm

2015-12-01

Jasmonates (JAs) are fatty acid derivatives that mediate many developmental processes and stress responses in plants. Synthetic jasmonate derivatives (commonly isotopically labeled), which mimic the action of the endogenous compounds are often employed as internal standards or probes to study metabolic processes. However, stable-isotope labeling of jasmonates does not allow the study of spatial and temporal distribution of these compounds in real time by positron emission tomography (PET). In this study, we explore whether a fluorinated jasmonate could mimic the action of the endogenous compound and therefore, be later employed as a tracer to study metabolic processes by PET. We describe the synthesis and the metabolism of (Z)-7-fluoro-8-(3-oxo-2-(pent-2-en-1-yl)cyclopentyl)octanoic acid (7F-OPC-8:0), a fluorinated analog of the JA precursor OPC-8:0. Like endogenous jasmonates, 7F-OPC-8:0 induces the transcription of marker jasmonate responsive genes (JRG) and the accumulation of jasmonates after its application to Arabidopsis thaliana plants. By using UHPLC-MS/MS, we could show that 7F-OPC-8:0 is metabolized in vivo similarly to the endogenous OPC-8:0. Furthermore, the fluorinated analog was successfully employed as a probe to show its translocation to undamaged systemic leaves when it was applied to wounded leaves. This result suggests that OPC-8:0 - and maybe other oxylipins - may contribute to the mobile signal which triggers systemic defense responses in plants. We highlight the potential of fluorinated oxylipins to study the mode of action of lipid-derived molecules in planta, either by conventional analytical methods or fluorine-based detection techniques. Copyright © 2015 Elsevier B.V. All rights reserved.
Ral signaling pathway in health and cancer.

PubMed

Moghadam, Adel Rezaei; Patrad, Elham; Tafsiri, Elham; Peng, Warner; Fangman, Benjamin; Pluard, Timothy J; Accurso, Anthony; Salacz, Michael; Shah, Kushal; Ricke, Brandon; Bi, Danse; Kimura, Kyle; Graves, Leland; Najad, Marzieh Khajoie; Dolatkhah, Roya; Sanaat, Zohreh; Yazdi, Mina; Tavakolinia, Naeimeh; Mazani, Mohammad; Amani, Mojtaba; Ghavami, Saeid; Gartell, Robyn; Reilly, Colleen; Naima, Zaid; Esfandyari, Tuba; Farassati, Faris

2017-12-01

The Ral (Ras-Like) signaling pathway plays an important role in the biology of cells. A plethora of effects is regulated by this signaling pathway and its prooncogenic effectors. Our team has demonstrated the overactivation of the RalA signaling pathway in a number of human malignancies including cancers of the liver, ovary, lung, brain, and malignant peripheral nerve sheath tumors. Additionally, we have shown that the activation of RalA in cancer stem cells is higher in comparison with differentiated cancer cells. In this article, we review the role of Ral signaling in health and disease with a focus on the role of this multifunctional protein in the generation of therapies for cancer. An improved understanding of this pathway can lead to development of a novel class of anticancer therapies that functions on the basis of intervention with RalA or its downstream effectors. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Jasmonates act positively in adventitious root formation in petunia cuttings.

PubMed

Lischweski, Sandra; Muchow, Anne; Guthörl, Daniela; Hause, Bettina

2015-09-22

Petunia is a model to study the process of adventitious root (AR) formation on leafy cuttings. Excision of cuttings leads to a transient increase in jasmonates, which is regarded as an early, transient and critical event for rooting. Here, the role of jasmonates in AR formation on petunia cuttings has been studied by a reverse genetic approach. To reduce the endogenous levels of jasmonates, transgenic plants were generated expressing a Petunia hybrida ALLENE OXIDE CYCLASE (PhAOC)-RNAi construct. The transgenic plants exhibited strongly reduced PhAOC transcript and protein levels as well as diminished accumulation of cis-12-oxo-phytodienoic acid, jasmonic acid and jasmonoyl-isoleucine after wounding in comparison to wild type and empty vector expressing plants. Reduced levels of endogenous jasmonates resulted in formation of lower numbers of ARs. However, this effect was not accompanied by altered levels of auxin and aminocyclopropane carboxylate (ACC, precursor of ethylene) or by impaired auxin and ethylene-induced gene expression. Neither activity of cell-wall invertases nor accumulation of soluble sugars was altered by jasmonate deficiency. Diminished numbers of AR in JA-deficient cuttings suggest that jasmonates act as positive regulators of AR formation in petunia wild type. However, wound-induced rise in jasmonate levels in petunia wild type cuttings seems not to be causal for increased auxin and ethylene levels and for sink establishment.
Role of the NFκB-signaling pathway in cancer

PubMed Central

Zhou, Yujuan; Lin, Jingguan; Wang, Heran; Oyang, Linda; Tian, Yutong; Liu, Lu; Su, Min; Wang, Hui; Cao, Deliang; Liao, Qianjin

2018-01-01

Cancer is a group of cells that malignantly grow and proliferate uncontrollably. At present, treatment modes for cancer mainly comprise surgery, chemotherapy, radiotherapy, molecularly targeted therapy, gene therapy, and immunotherapy. However, the curative effects of these treatments have been limited thus far by specific characteristics of tumors. Abnormal activation of signaling pathways is involved in tumor pathogenesis and plays critical roles in growth, progression, and relapse of cancers. Targeted therapies against effectors in oncogenic signaling have improved the outcomes of cancer patients. NFκB is an important signaling pathway involved in pathogenesis and treatment of cancers. Excessive activation of the NFκB-signaling pathway has been documented in various tumor tissues, and studies on this signaling pathway for targeted cancer therapy have become a hot topic. In this review, we update current understanding of the NFκB-signaling pathway in cancer. PMID:29695914

Low oleic acid-derived repression of jasmonic acid-inducible defense responses requires the WRKY50 and WRKY51 proteins

USDA-ARS?s Scientific Manuscript database

Signaling induced upon a reduction in oleic acid (18:1) levels simultaneously up-regulates salicylic acid (SA)-mediated responses and inhibits jasmonic acid (JA)-inducible defenses, resulting in enhanced resistance to biotrophs but increased susceptibility to necrotrophs. SA and the signaling compon...
The Fibroblast Growth Factor signaling pathway.

PubMed

Ornitz, David M; Itoh, Nobuyuki

2015-01-01

The signaling component of the mammalian Fibroblast Growth Factor (FGF) family is comprised of eighteen secreted proteins that interact with four signaling tyrosine kinase FGF receptors (FGFRs). Interaction of FGF ligands with their signaling receptors is regulated by protein or proteoglycan cofactors and by extracellular binding proteins. Activated FGFRs phosphorylate specific tyrosine residues that mediate interaction with cytosolic adaptor proteins and the RAS-MAPK, PI3K-AKT, PLCγ, and STAT intracellular signaling pathways. Four structurally related intracellular non-signaling FGFs interact with and regulate the family of voltage gated sodium channels. Members of the FGF family function in the earliest stages of embryonic development and during organogenesis to maintain progenitor cells and mediate their growth, differentiation, survival, and patterning. FGFs also have roles in adult tissues where they mediate metabolic functions, tissue repair, and regeneration, often by reactivating developmental signaling pathways. Consistent with the presence of FGFs in almost all tissues and organs, aberrant activity of the pathway is associated with developmental defects that disrupt organogenesis, impair the response to injury, and result in metabolic disorders, and cancer. For further resources related to this article, please visit the WIREs website. © 2015 The Authors. WIREs Developmental Biology published by Wiley Periodicals, Inc.
Parthenolide accumulation and expression of genes related to parthenolide biosynthesis affected by exogenous application of methyl jasmonate and salicylic acid in Tanacetum parthenium.

PubMed

Majdi, Mohammad; Abdollahi, Mohammad Reza; Maroufi, Asad

2015-11-01

Up-regulation of germacrene A synthase and down-regulation of parthenolide hydroxylase genes play key role in parthenolide accumulation of feverfew plants treated with methyl jasmonate and salicylic acid. Parthenolide is an important sesquiterpene lactone due to its anti-migraine and anti-cancer properties. Parthenolide amount was quantified by high-performance liquid chromatography after foliar application of methyl jasmonate (100 µM) or salicylic acid (1.0 mM) on feverfew leaves in time course experiment (3-96 h). Results indicate that exogenous application of methyl jasmonate or salicylic acid activated parthenolide biosynthesis. Parthenolide content reached its highest amount at 24 h after methyl jasmonate or salicylic acid treatments, which were 3.1- and 1.96-fold higher than control plants, respectively. Parthenolide transiently increased due to methyl jasmonate or salicylic acid treatments until 24 h, but did not show significant difference compared with control plants at 48 and 96 h time points in both treatments. Also, the transcript levels of early pathway (upstream) genes of terpene biosynthesis including 3-hydroxy-3-methylglutaryl-coenzyme A reductase, 1-deoxy-D-xylulose-5-phosphate reductoisomerase and hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase and the biosynthetic genes of parthenolide including germacrene A synthase, germacrene A oxidase, costunolide synthase and parthenolide synthase were increased by methyl jasmonate and salicylic acid treatments, but with different intensity. The transcriptional levels of these genes were higher in methyl jasmonate-treated plants than salicylic acid-treated plants. Parthenolide content measurements along with expression pattern analysis of the aforementioned genes and parthenolide hydroxylase as side branch gene of parthenolide suggest that the expression patterns of early pathway genes were not directly consistent with parthenolide accumulation pattern; hence, parthenolide accumulation is
The Basic Helix-Loop-Helix Transcription Factor MYC2 Directly Represses PLETHORA Expression during Jasmonate-Mediated Modulation of the Root Stem Cell Niche in Arabidopsis[W][OA

PubMed Central

Chen, Qian; Sun, Jiaqiang; Zhai, Qingzhe; Zhou, Wenkun; Qi, Linlin; Xu, Li; Wang, Bao; Chen, Rong; Jiang, Hongling; Qi, Jing; Li, Xugang; Palme, Klaus; Li, Chuanyou

2011-01-01

The root stem cell niche, which in the Arabidopsis thaliana root meristem is an area of four mitotically inactive quiescent cells (QCs) and the surrounding mitotically active stem cells, is critical for root development and growth. We report here that during jasmonate-induced inhibition of primary root growth, jasmonate reduces root meristem activity and leads to irregular QC division and columella stem cell differentiation. Consistently, jasmonate reduces the expression levels of the AP2-domain transcription factors PLETHORA1 (PLT1) and PLT2, which form a developmentally instructive protein gradient and mediate auxin-induced regulation of stem cell niche maintenance. Not surprisingly, the effects of jasmonate on root stem cell niche maintenance and PLT expression require the functioning of MYC2/JASMONATE INSENSITIVE1, a basic helix-loop-helix transcription factor that involves versatile aspects of jasmonate-regulated gene expression. Gel shift and chromatin immunoprecipitation experiments reveal that MYC2 directly binds the promoters of PLT1 and PLT2 and represses their expression. We propose that MYC2-mediated repression of PLT expression integrates jasmonate action into the auxin pathway in regulating root meristem activity and stem cell niche maintenance. This study illustrates a molecular framework for jasmonate-induced inhibition of root growth through interaction with the growth regulator auxin. PMID:21954460
Jasmonate-triggered plant immunity.

PubMed

Campos, Marcelo L; Kang, Jin-Ho; Howe, Gregg A

2014-07-01

The plant hormone jasmonate (JA) exerts direct control over the production of chemical defense compounds that confer resistance to a remarkable spectrum of plant-associated organisms, ranging from microbial pathogens to vertebrate herbivores. The underlying mechanism of JA-triggered immunity (JATI) can be conceptualized as a multi-stage signal transduction cascade involving: i) pattern recognition receptors (PRRs) that couple the perception of danger signals to rapid synthesis of bioactive JA; ii) an evolutionarily conserved JA signaling module that links fluctuating JA levels to changes in the abundance of transcriptional repressor proteins; and iii) activation (de-repression) of transcription factors that orchestrate the expression of myriad chemical and morphological defense traits. Multiple negative feedback loops act in concert to restrain the duration and amplitude of defense responses, presumably to mitigate potential fitness costs of JATI. The convergence of diverse plant- and non-plant-derived signals on the core JA module indicates that JATI is a general response to perceived danger. However, the modular structure of JATI may accommodate attacker-specific defense responses through evolutionary innovation of PRRs (inputs) and defense traits (outputs). The efficacy of JATI as a defense strategy is highlighted by its capacity to shape natural populations of plant attackers, as well as the propensity of plant-associated organisms to subvert or otherwise manipulate JA signaling. As both a cellular hub for integrating informational cues from the environment and a common target of pathogen effectors, the core JA module provides a focal point for understanding immune system networks and the evolution of chemical diversity in the plant kingdom.
Systematic analysis of signaling pathways using an integrative environment.

PubMed

Visvanathan, Mahesh; Breit, Marc; Pfeifer, Bernhard; Baumgartner, Christian; Modre-Osprian, Robert; Tilg, Bernhard

2007-01-01

Understanding the biological processes of signaling pathways as a whole system requires an integrative software environment that has comprehensive capabilities. The environment should include tools for pathway design, visualization, simulation and a knowledge base concerning signaling pathways as one. In this paper we introduce a new integrative environment for the systematic analysis of signaling pathways. This system includes environments for pathway design, visualization, simulation and a knowledge base that combines biological and modeling information concerning signaling pathways that provides the basic understanding of the biological system, its structure and functioning. The system is designed with a client-server architecture. It contains a pathway designing environment and a simulation environment as upper layers with a relational knowledge base as the underlying layer. The TNFa-mediated NF-kB signal trans-duction pathway model was designed and tested using our integrative framework. It was also useful to define the structure of the knowledge base. Sensitivity analysis of this specific pathway was performed providing simulation data. Then the model was extended showing promising initial results. The proposed system offers a holistic view of pathways containing biological and modeling data. It will help us to perform biological interpretation of the simulation results and thus contribute to a better understanding of the biological system for drug identification.
Pathogen exploitation of an abscisic acid- and jasmonate-inducible MAPK phosphatase and its interception by Arabidopsis immunity.

PubMed

Mine, Akira; Berens, Matthias L; Nobori, Tatsuya; Anver, Shajahan; Fukumoto, Kaori; Winkelmüller, Thomas M; Takeda, Atsushi; Becker, Dieter; Tsuda, Kenichi

2017-07-11

Phytopathogens promote virulence by, for example, exploiting signaling pathways mediated by phytohormones such as abscisic acid (ABA) and jasmonate (JA). Some plants can counteract pathogen virulence by invoking a potent form of immunity called effector-triggered immunity (ETI). Here, we report that ABA and JA mediate inactivation of the immune-associated MAP kinases (MAPKs), MPK3 and MPK6, in Arabidopsis thaliana ABA induced expression of genes encoding the protein phosphatases 2C (PP2Cs), HAI1 , HAI2 , and HAI3 through ABF/AREB transcription factors. These three HAI PP2Cs interacted with MPK3 and MPK6 and were required for ABA-mediated MPK3/MPK6 inactivation and immune suppression. The bacterial pathogen Pseudomonas syringae pv. tomato ( Pto ) DC3000 activates ABA signaling and produces a JA-mimicking phytotoxin, coronatine (COR), that promotes virulence. We found that Pto DC3000 induces HAI1 through COR-mediated activation of MYC2, a master transcription factor in JA signaling. HAI1 dephosphorylated MPK3 and MPK6 in vitro and was necessary for COR-mediated suppression of MPK3/MPK6 activation and immunity. Intriguingly, upon ETI activation, A. thaliana plants overcame the HAI1-dependent virulence of COR by blocking JA signaling. Finally, we showed conservation of induction of HAI PP2Cs by ABA and JA in other Brassicaceae species. Taken together, these results suggest that ABA and JA signaling pathways, which are hijacked by the bacterial pathogen, converge on the HAI PP2Cs that suppress activation of the immune-associated MAPKs. Also, our data unveil interception of JA-signaling activation as a host counterstrategy against the bacterial suppression of MAPKs during ETI.
Small RNA-seq analysis in response to methyl jasmonate and abscisic acid treatment in Persicaria minor.

PubMed

Nazaruddin, Nazaruddin; Samad, Abdul Fatah A; Sajad, Muhammad; Jani, Jaeyres; Zainal, Zamri; Ismail, Ismanizan

2017-06-01

Persicaria minor (Kesum) is an important medicinal plant with high level of secondary metabolite contents, especially, terpenoids and flavonoids. Previous studies have revealed that application of exogenous phytohormone could increase secondary metabolite contents of the plant. MicroRNAs (miRNAs) are small RNAs that play important regulatory roles in various biological processes. In order to explore the possible role of miRNA in the regulation of these phytohormones signaling pathway and uncovering their potential correlation, we, for the first time, have generated the smallRNA library of Kesum plant. The library was developed in response to methyl jasmonate (MJ) and abscisic acid (ABA) treatment by using next-generation sequencing technology. Raw reads have been deposited to SRA database with the accession numbers, SRX2655642 and SRX2655643 (MJ-treated), SRXSRX2655644 and SRX2655645 (ABA-treated) and SRX2655646and SRX2655647 (Control).
Redox signaling in plants.

PubMed

Foyer, Christine H; Noctor, Graham

2013-06-01

Our aim is to deliver an authoritative and challenging perspective of current concepts in plant redox signaling, focusing particularly on the complex interface between the redox and hormone-signaling pathways that allow precise control of plant growth and defense in response to metabolic triggers and environmental constraints and cues. Plants produce significant amounts of singlet oxygen and other reactive oxygen species (ROS) as a result of photosynthetic electron transport and metabolism. Such pathways contribute to the compartment-specific redox-regulated signaling systems in plant cells that convey information to the nucleus to regulate gene expression. Like the chloroplasts and mitochondria, the apoplast-cell wall compartment makes a significant contribution to the redox signaling network, but unlike these organelles, the apoplast has a low antioxidant-buffering capacity. The respective roles of ROS, low-molecular antioxidants, redox-active proteins, and antioxidant enzymes are considered in relation to the functions of plant hormones such as salicylic acid, jasmonic acid, and auxin, in the composite control of plant growth and defense. Regulation of redox gradients between key compartments in plant cells such as those across the plasma membrane facilitates flexible and multiple faceted opportunities for redox signaling that spans the intracellular and extracellular environments. In conclusion, plants are recognized as masters of the art of redox regulation that use oxidants and antioxidants as flexible integrators of signals from metabolism and the environment.
Jasmonic acid distribution and action in plants: regulation during development and response to biotic and abiotic stress.

PubMed Central

Creelman, R A; Mullet, J E

1995-01-01

Jasmonic acid (JA) is a naturally occurring growth regulator found in higher plants. Several physiological roles have been described for this compound (or a related compound, methyl jasmonate) during plant development and in response to biotic and abiotic stress. To accurately determine JA levels in plant tissue, we have synthesized JA containing 13C for use as an internal standard with an isotopic composition of [225]:[224] 0.98:0.02 compared with [225]:[224] 0.15:0.85 for natural material. GC analysis (flame ionization detection and MS) indicate that the internal standard is composed of 92% 2-(+/-)-[13C]JA and 8% 2-(+/-)-7-iso-[13C]JA. In soybean plants, JA levels were highest in young leaves, flowers, and fruit (highest in the pericarp). In soybean seeds and seedlings, JA levels were highest in the youngest organs including the hypocotyl hook, plumule, and 12-h axis. In soybean leaves that had been dehydrated to cause a 15% decrease in fresh weight, JA levels increased approximately 5-fold within 2 h and declined to approximately control levels by 4 h. In contrast, a lag time of 1-2 h occurred before abscisic acid accumulation reached a maximum. These results will be discussed in the context of multiple pathways for JA biosynthesis and the role of JA in plant development and responses to environmental signals. PMID:11607536
Jasmonic acid distribution and action in plants: regulation during development and response to biotic and abiotic stress.

PubMed

Creelman, R A; Mullet, J E

1995-05-09

Jasmonic acid (JA) is a naturally occurring growth regulator found in higher plants. Several physiological roles have been described for this compound (or a related compound, methyl jasmonate) during plant development and in response to biotic and abiotic stress. To accurately determine JA levels in plant tissue, we have synthesized JA containing 13C for use as an internal standard with an isotopic composition of [225]:[224] 0.98:0.02 compared with [225]:[224] 0.15:0.85 for natural material. GC analysis (flame ionization detection and MS) indicate that the internal standard is composed of 92% 2-(+/-)-[13C]JA and 8% 2-(+/-)-7-iso-[13C]JA. In soybean plants, JA levels were highest in young leaves, flowers, and fruit (highest in the pericarp). In soybean seeds and seedlings, JA levels were highest in the youngest organs including the hypocotyl hook, plumule, and 12-h axis. In soybean leaves that had been dehydrated to cause a 15% decrease in fresh weight, JA levels increased approximately 5-fold within 2 h and declined to approximately control levels by 4 h. In contrast, a lag time of 1-2 h occurred before abscisic acid accumulation reached a maximum. These results will be discussed in the context of multiple pathways for JA biosynthesis and the role of JA in plant development and responses to environmental signals.
ORA47 (octadecanoid-responsive AP2/ERF-domain transcription factor 47) regulates jasmonic acid and abscisic acid biosynthesis and signaling through binding to a novel cis-element.

PubMed

Chen, Hsing-Yu; Hsieh, En-Jung; Cheng, Mei-Chun; Chen, Chien-Yu; Hwang, Shih-Ying; Lin, Tsan-Piao

2016-07-01

ORA47 (octadecanoid-responsive AP2/ERF-domain transcription factor 47) of Arabidopsis thaliana is an AP2/ERF domain transcription factor that regulates jasmonate (JA) biosynthesis and is induced by methyl JA treatment. The regulatory mechanism of ORA47 remains unclear. ORA47 is shown to bind to the cis-element (NC/GT)CGNCCA, which is referred to as the O-box, in the promoter of ABI2. We proposed that ORA47 acts as a connection between ABA INSENSITIVE1 (ABI1) and ABI2 and mediates an ABI1-ORA47-ABI2 positive feedback loop. PORA47:ORA47-GFP transgenic plants were used in a chromatin immunoprecipitation (ChIP) assay to show that ORA47 participates in the biosynthesis and/or signaling pathways of nine phytohormones. Specifically, many abscisic acid (ABA) and JA biosynthesis and signaling genes were direct targets of ORA47 under stress conditions. The JA content of the P35S:ORA47-GR lines was highly induced under wounding and moderately induced under water stress relative to that of the wild-type plants. The wounding treatment moderately increased ABA accumulation in the transgenic lines, whereas the water stress treatment repressed the ABA content. ORA47 is proposed to play a role in the biosynthesis of JA and ABA and in regulating the biosynthesis and/or signaling of a suite of phytohormone genes when plants are subjected to wounding and water stress. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.
Molecular Pathways: Hippo Signaling, a Critical Tumor Suppressor.

PubMed

Sebio, Ana; Lenz, Heinz-Josef

2015-11-15

The Salvador-Warts-Hippo pathway controls cell fate and tissue growth. The main function of the Hippo pathway is to prevent YAP and TAZ translocation to the nucleus where they induce the transcription of genes involved in cell proliferation, survival, and stem cell maintenance. Hippo signaling is, thus, a complex tumor suppressor, and its deregulation is a key feature in many cancers. Recent mounting evidence suggests that the overexpression of Hippo components can be useful prognostic biomarkers. Moreover, Hippo signaling appears to be intimately linked to some of the most important signaling pathways involved in cancer development and progression. A better understanding of the Hippo pathway is thus essential to untangle tumor biology and to develop novel anticancer therapies. Here, we comment on the progress made in understanding Hippo signaling and its connections, and also on how new drugs modulating this pathway, such as Verteporfin and C19, are highly promising cancer therapeutics. ©2015 American Association for Cancer Research.
Rhamnolipids elicit defense responses and induce disease resistance against biotrophic, hemibiotrophic, and necrotrophic pathogens that require different signaling pathways in Arabidopsis and highlight a central role for salicylic acid.

PubMed

Sanchez, Lisa; Courteaux, Barbara; Hubert, Jane; Kauffmann, Serge; Renault, Jean-Hugues; Clément, Christophe; Baillieul, Fabienne; Dorey, Stéphan

2012-11-01

Plant resistance to phytopathogenic microorganisms mainly relies on the activation of an innate immune response usually launched after recognition by the plant cells of microbe-associated molecular patterns. The plant hormones, salicylic acid (SA), jasmonic acid, and ethylene have emerged as key players in the signaling networks involved in plant immunity. Rhamnolipids (RLs) are glycolipids produced by bacteria and are involved in surface motility and biofilm development. Here we report that RLs trigger an immune response in Arabidopsis (Arabidopsis thaliana) characterized by signaling molecules accumulation and defense gene activation. This immune response participates to resistance against the hemibiotrophic bacterium Pseudomonas syringae pv tomato, the biotrophic oomycete Hyaloperonospora arabidopsidis, and the necrotrophic fungus Botrytis cinerea. We show that RL-mediated resistance involves different signaling pathways that depend on the type of pathogen. Ethylene is involved in RL-induced resistance to H. arabidopsidis and to P. syringae pv tomato whereas jasmonic acid is essential for the resistance to B. cinerea. SA participates to the restriction of all pathogens. We also show evidence that SA-dependent plant defenses are potentiated by RLs following challenge by B. cinerea or P. syringae pv tomato. These results highlight a central role for SA in RL-mediated resistance. In addition to the activation of plant defense responses, antimicrobial properties of RLs are thought to participate in the protection against the fungus and the oomycete. Our data highlight the intricate mechanisms involved in plant protection triggered by a new type of molecule that can be perceived by plant cells and that can also act directly onto pathogens.
Signaling Pathways in Cardiac Myocyte Apoptosis

PubMed Central

Xia, Peng; Liu, Yuening

2016-01-01

Cardiovascular diseases, the number 1 cause of death worldwide, are frequently associated with apoptotic death of cardiac myocytes. Since cardiomyocyte apoptosis is a highly regulated process, pharmacological intervention of apoptosis pathways may represent a promising therapeutic strategy for a number of cardiovascular diseases and disorders including myocardial infarction, ischemia/reperfusion injury, chemotherapy cardiotoxicity, and end-stage heart failure. Despite rapid growth of our knowledge in apoptosis signaling pathways, a clinically applicable treatment targeting this cellular process is currently unavailable. To help identify potential innovative directions for future research, it is necessary to have a full understanding of the apoptotic pathways currently known to be functional in cardiac myocytes. Here, we summarize recent progress in the regulation of cardiomyocyte apoptosis by multiple signaling molecules and pathways, with a focus on the involvement of these pathways in the pathogenesis of heart disease. In addition, we provide an update regarding bench to bedside translation of this knowledge and discuss unanswered questions that need further investigation. PMID:28101515
Targeting the Hippo signalling pathway for cancer treatment.

PubMed

Nakatani, Keisuke; Maehama, Tomohiko; Nishio, Miki; Goto, Hiroki; Kato, Wakako; Omori, Hirofumi; Miyachi, Yosuke; Togashi, Hideru; Shimono, Yohei; Suzuki, Akira

2017-03-01

The Hippo signalling pathway monitors cell-cell contact and external factors that shape tissue structure. In mice, tumourigenesis and developmental abnormalities are common consequences of dysregulated Hippo signalling. Expression of Hippo pathway components is also frequently altered in human tumours and correlates with poor prognosis and reduced patient survival. Thus, the Hippo pathway is an attractive anti-cancer target. Here, we provide an overview of the function and regulation of Hippo signalling components and summarize progress to date on the development of agents able to regulate Hippo signalling for cancer therapy. © The Authors 2016. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.
Sink limitation induces the expression of multiple soybean vegetative lipoxygenase mRNAs while the endogenous jasmonic acid level remains low.

PubMed Central

Bunker, T W; Koetje, D S; Stephenson, L C; Creelman, R A; Mullet, J E; Grimes, H D

1995-01-01

The response of individual members of the lipoxygenase multigene family in soybeans to sink deprivation was analyzed. RNase protection assays indicated that a novel vegetative lipoxygenase gene, vlxC, and three other vegetative lipoxygenase mRNAs accumulated in mature leaves in response to a variety of sink limitations. These data suggest that several members of the lipoxygenase multigene family are involved in assimilate partitioning. The possible involvement of jasmonic acid as a signaling molecule regulating assimilate partitioning into the vegetative storage proteins and lipoxygenases was directly assessed by determining the endogenous level of jasmonic acid in leaves from plants with their pods removed. There was no rise in the level of endogenous jasmonic acid coincident with the strong increase in both vlxC and vegetative storage protein VspB transcripts in response to sink limitation. Thus, expression of the vegetative lipoxygenases and vegetative storage proteins is not regulated by jasmonic acid in sink-limited leaves. PMID:7549487
Sink limitation induces the expression of multiple soybean vegetative lipoxygenase mRNAs while the endogenous jasmonic acid level remains low.

PubMed

Bunker, T W; Koetje, D S; Stephenson, L C; Creelman, R A; Mullet, J E; Grimes, H D

1995-08-01

The response of individual members of the lipoxygenase multigene family in soybeans to sink deprivation was analyzed. RNase protection assays indicated that a novel vegetative lipoxygenase gene, vlxC, and three other vegetative lipoxygenase mRNAs accumulated in mature leaves in response to a variety of sink limitations. These data suggest that several members of the lipoxygenase multigene family are involved in assimilate partitioning. The possible involvement of jasmonic acid as a signaling molecule regulating assimilate partitioning into the vegetative storage proteins and lipoxygenases was directly assessed by determining the endogenous level of jasmonic acid in leaves from plants with their pods removed. There was no rise in the level of endogenous jasmonic acid coincident with the strong increase in both vlxC and vegetative storage protein VspB transcripts in response to sink limitation. Thus, expression of the vegetative lipoxygenases and vegetative storage proteins is not regulated by jasmonic acid in sink-limited leaves.
Control of Carbon Assimilation and Partitioning by Jasmonate: An Accounting of Growth-Defense Tradeoffs.

PubMed

Havko, Nathan E; Major, Ian T; Jewell, Jeremy B; Attaran, Elham; Browse, John; Howe, Gregg A

2016-01-15

Plant growth is often constrained by the limited availability of resources in the microenvironment. Despite the continuous threat of attack from insect herbivores and pathogens, investment in defense represents a lost opportunity to expand photosynthetic capacity in leaves and absorption of nutrients and water by roots. To mitigate the metabolic expenditure on defense, plants have evolved inducible defense strategies. The plant hormone jasmonate (JA) is a key regulator of many inducible defenses. Synthesis of JA in response to perceived danger leads to the deployment of a variety of defensive structures and compounds, along with a potent inhibition of growth. Genetic studies have established an important role for JA in mediating tradeoffs between growth and defense. However, several gaps remain in understanding of how JA signaling inhibits growth, either through direct transcriptional control of JA-response genes or crosstalk with other signaling pathways. Here, we highlight recent progress in uncovering the role of JA in controlling growth-defense balance and its relationship to resource acquisition and allocation. We also discuss tradeoffs in the context of the ability of JA to promote increased leaf mass per area (LMA), which is a key indicator of leaf construction costs and leaf life span.
Computational identification of signalling pathways in Plasmodium falciparum.

PubMed

Oyelade, Jelili; Ewejobi, Itunu; Brors, Benedikt; Eils, Roland; Adebiyi, Ezekiel

2011-06-01

Malaria is one of the world's most common and serious diseases causing death of about 3 million people each year. Its most severe occurrence is caused by the protozoan Plasmodium falciparum. Reports have shown that the resistance of the parasite to existing drugs is increasing. Therefore, there is a huge and urgent need to discover and validate new drug or vaccine targets to enable the development of new treatments for malaria. The ability to discover these drug or vaccine targets can only be enhanced from our deep understanding of the detailed biology of the parasite, for example how cells function and how proteins organize into modules such as metabolic, regulatory and signal transduction pathways. It has been noted that the knowledge of signalling transduction pathways in Plasmodium is fundamental to aid the design of new strategies against malaria. This work uses a linear-time algorithm for finding paths in a network under modified biologically motivated constraints. We predicted several important signalling transduction pathways in Plasmodium falciparum. We have predicted a viable signalling pathway characterized in terms of the genes responsible that may be the PfPKB pathway recently elucidated in Plasmodium falciparum. We obtained from the FIKK family, a signal transduction pathway that ends up on a chloroquine resistance marker protein, which indicates that interference with FIKK proteins might reverse Plasmodium falciparum from resistant to sensitive phenotype. We also proposed a hypothesis that showed the FIKK proteins in this pathway as enabling the resistance parasite to have a mechanism for releasing chloroquine (via an efflux process). Furthermore, we also predicted a signalling pathway that may have been responsible for signalling the start of the invasion process of Red Blood Cell (RBC) by the merozoites. It has been noted that the understanding of this pathway will give insight into the parasite virulence and will facilitate rational vaccine design

Intricacies of hedgehog signaling pathways: A perspective in tumorigenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kar, Swayamsiddha; Deb, Moonmoon; Sengupta, Dipta

The hedgehog (HH) signaling pathway is a crucial negotiator of developmental proceedings in the embryo governing a diverse array of processes including cell proliferation, differentiation, and tissue patterning. The overall activity of the pathway is significantly curtailed after embryogenesis as well as in adults, yet it retains many of its functional capacities. However, aberration in HH signaling mediates the initiation, proliferation and continued sustenance of malignancy in different tissues to varying degrees through different mechanisms. In this review, we provide an overview of the role of constitutively active aberrant HH signaling pathway in different types of human cancer and themore » underlying molecular and genetic mechanisms that drive tumorigenesis in that particular tissue. An insight into the various modes of anomalous HH signaling in different organs will provide a comprehensive knowledge of the pathway in these tissues and open a window for individually tailored, tissue-specific therapeutic interventions. The synergistic cross talking of HH pathway with many other regulatory molecules and developmentally inclined signaling pathways may offer many avenues for pharmacological advances. Understanding the molecular basis of abnormal HH signaling in cancer will provide an opportunity to inhibit the deregulated pathway in many aggressive and therapeutically challenging cancers where promising options are not available.« less
Effects of jasmonic acid, ethylene, and salicylic acid signaling on the rhizosphere bacterial community of Arabidopsis thaliana.

PubMed

Doornbos, Rogier F; Geraats, Bart P J; Kuramae, Eiko E; Van Loon, L C; Bakker, Peter A H M

2011-04-01

Systemically induced resistance is a promising strategy to control plant diseases, as it affects numerous pathogens. However, since induced resistance reduces one or both growth and activity of plant pathogens, the indigenous microflora may also be affected by an enhanced defensive state of the plant. The aim of this study was to elucidate how much the bacterial rhizosphere microflora of Arabidopsis is affected by induced systemic resistance (ISR) or systemic acquired resistance (SAR). Therefore, the bacterial microflora of wild-type plants and plants affected in their defense signaling was compared. Additionally, ISR was induced by application of methyl jasmonate and SAR by treatment with salicylic acid or benzothiadiazole. As a comparative model, we also used wild type and ethylene-insensitive tobacco. Some of the Arabidopsis genotypes affected in defense signaling showed altered numbers of culturable bacteria in their rhizospheres; however, effects were dependent on soil type. Effects of plant genotype on rhizosphere bacterial community structure could not be related to plant defense because chemical activation of ISR or SAR had no significant effects on density and structure of the rhizosphere bacterial community. These findings support the notion that control of plant diseases by elicitation of systemic resistance will not significantly affect the resident soil bacterial microflora.
[Signaling pathways mTOR and AKT in epilepsy].

PubMed

Romero-Leguizamon, C R; Ramirez-Latorre, J A; Mora-Munoz, L; Guerrero-Naranjo, A

2016-07-01

The signaling pathway AKT/mTOR is a central axis in regulating cellular processes, particularly in neurological diseases. In the case of epilepsy, it has been observed alteration in the pathophysiological process of the same. However, they have not described all the mechanisms of these signaling pathways that could open the opportunity to new research and therapeutic strategies. To review existing partnerships between intracellular signaling pathways AKT and mTOR in the pathophysiology of epilepsy. Epilepsy is a disease with a high epidemiological impact globally, so it is widely investigated regarding the pathophysiological components thereof. In that search they have been involved different intracellular signaling pathways in neurons, as determinants epileptogenic. Advances in this field have even allowed the successful implementation of new therapeutic strategies and to open the way to new research in the field. Improving knowledge about the pathophysiological role of the signaling pathway mTOR/AKT in epilepsy can raise new investigations regarding therapeutic alternatives. The use of mTOR inhibitors, has emerged in recent years as effective in treating this disease entity alternative however is clear the necessity of continue the research for new drug therapies.
The Hippo signaling pathway provides novel anti-cancer drug targets

PubMed Central

Bae, June Sung; Kim, Sun Mi; Lee, Ho

2017-01-01

The Hippo signaling pathway plays a crucial role in cell proliferation, apoptosis, differentiation, and development. Major effectors of the Hippo signaling pathway include the transcriptional co-activators Yes-associated protein 1 (YAP) and WW domain-containing transcription regulator protein 1 (TAZ). The transcriptional activities of YAP and TAZ are affected by interactions with proteins from many diverse signaling pathways as well as responses to the external environment. High YAP and TAZ activity has been observed in many cancer types, and functional dysregulation of Hippo signaling enhances the oncogenic properties of YAP and TAZ and promotes cancer development. Many biological elements, including mechanical strain on the cell, cell polarity/adhesion molecules, other signaling pathways (e.g., G-protein-coupled receptor, epidermal growth factor receptor, Wnt, Notch, and transforming growth factor β/bone morphogenic protein), and cellular metabolic status, can promote oncogenesis through synergistic association with components of the Hippo signaling pathway. Here, we review the signaling networks that interact with the Hippo signaling pathway and discuss the potential of using drugs that inhibit YAP and TAZ activity for cancer therapy. PMID:28035075
The Hippo signaling pathway provides novel anti-cancer drug targets.

PubMed

Bae, June Sung; Kim, Sun Mi; Lee, Ho

2017-02-28

The Hippo signaling pathway plays a crucial role in cell proliferation, apoptosis, differentiation, and development. Major effectors of the Hippo signaling pathway include the transcriptional co-activators Yes-associated protein 1 (YAP) and WW domain-containing transcription regulator protein 1 (TAZ). The transcriptional activities of YAP and TAZ are affected by interactions with proteins from many diverse signaling pathways as well as responses to the external environment. High YAP and TAZ activity has been observed in many cancer types, and functional dysregulation of Hippo signaling enhances the oncogenic properties of YAP and TAZ and promotes cancer development. Many biological elements, including mechanical strain on the cell, cell polarity/adhesion molecules, other signaling pathways (e.g., G-protein-coupled receptor, epidermal growth factor receptor, Wnt, Notch, and transforming growth factor β/bone morphogenic protein), and cellular metabolic status, can promote oncogenesis through synergistic association with components of the Hippo signaling pathway. Here, we review the signaling networks that interact with the Hippo signaling pathway and discuss the potential of using drugs that inhibit YAP and TAZ activity for cancer therapy.
Triggering signaling pathways using F-actin self-organization.

PubMed

Colin, A; Bonnemay, L; Gayrard, C; Gautier, J; Gueroui, Z

2016-10-04

The spatiotemporal organization of proteins within cells is essential for cell fate behavior. Although it is known that the cytoskeleton is vital for numerous cellular functions, it remains unclear how cytoskeletal activity can shape and control signaling pathways in space and time throughout the cell cytoplasm. Here we show that F-actin self-organization can trigger signaling pathways by engineering two novel properties of the microfilament self-organization: (1) the confinement of signaling proteins and (2) their scaffolding along actin polymers. Using in vitro reconstitutions of cellular functions, we found that both the confinement of nanoparticle-based signaling platforms powered by F-actin contractility and the scaffolding of engineered signaling proteins along actin microfilaments can drive a signaling switch. Using Ran-dependent microtubule nucleation, we found that F-actin dynamics promotes the robust assembly of microtubules. Our in vitro assay is a first step towards the development of novel bottom-up strategies to decipher the interplay between cytoskeleton spatial organization and signaling pathway activity.
Triggering signaling pathways using F-actin self-organization

PubMed Central

Colin, A.; Bonnemay, L.; Gayrard, C.; Gautier, J.; Gueroui, Z.

2016-01-01

The spatiotemporal organization of proteins within cells is essential for cell fate behavior. Although it is known that the cytoskeleton is vital for numerous cellular functions, it remains unclear how cytoskeletal activity can shape and control signaling pathways in space and time throughout the cell cytoplasm. Here we show that F-actin self-organization can trigger signaling pathways by engineering two novel properties of the microfilament self-organization: (1) the confinement of signaling proteins and (2) their scaffolding along actin polymers. Using in vitro reconstitutions of cellular functions, we found that both the confinement of nanoparticle-based signaling platforms powered by F-actin contractility and the scaffolding of engineered signaling proteins along actin microfilaments can drive a signaling switch. Using Ran-dependent microtubule nucleation, we found that F-actin dynamics promotes the robust assembly of microtubules. Our in vitro assay is a first step towards the development of novel bottom-up strategies to decipher the interplay between cytoskeleton spatial organization and signaling pathway activity. PMID:27698406
Circadian Stress Regimes Affect the Circadian Clock and Cause Jasmonic Acid-Dependent Cell Death in Cytokinin-Deficient Arabidopsis Plants[OPEN

PubMed Central

Nitschke, Silvia; Cortleven, Anne; Iven, Tim; Havaux, Michel; Schmülling, Thomas

2016-01-01

The circadian clock helps plants measure daylength and adapt to changes in the day-night rhythm. We found that changes in the light-dark regime triggered stress responses, eventually leading to cell death, in leaves of Arabidopsis thaliana plants with reduced cytokinin levels or defective cytokinin signaling. Prolonged light treatment followed by a dark period induced stress and cell death marker genes while reducing photosynthetic efficiency. This response, called circadian stress, is also characterized by altered expression of clock and clock output genes. In particular, this treatment strongly reduced the expression of CIRCADIAN CLOCK ASSOCIATED1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY). Intriguingly, similar changes in gene expression and cell death were observed in clock mutants lacking proper CCA1 and LHY function. Circadian stress caused strong changes in reactive oxygen species- and jasmonic acid (JA)-related gene expression. The activation of the JA pathway, involving the accumulation of JA metabolites, was crucial for the induction of cell death, since the cell death phenotype was strongly reduced in the jasmonate resistant1 mutant background. We propose that adaptation to circadian stress regimes requires a normal cytokinin status which, acting primarily through the AHK3 receptor, supports circadian clock function to guard against the detrimental effects of circadian stress. PMID:27354555
SPV: a JavaScript Signaling Pathway Visualizer.

PubMed

Calderone, Alberto; Cesareni, Gianni

2018-03-24

The visualization of molecular interactions annotated in web resources is useful to offer to users such information in a clear intuitive layout. These interactions are frequently represented as binary interactions that are laid out in free space where, different entities, cellular compartments and interaction types are hardly distinguishable. SPV (Signaling Pathway Visualizer) is a free open source JavaScript library which offers a series of pre-defined elements, compartments and interaction types meant to facilitate the representation of signaling pathways consisting of causal interactions without neglecting simple protein-protein interaction networks. freely available under Apache version 2 license; Source code: https://github.com/Sinnefa/SPV_Signaling_Pathway_Visualizer_v1.0. Language: JavaScript; Web technology: Scalable Vector Graphics; Libraries: D3.js. sinnefa@gmail.com.
Aldolase positively regulates of the canonical Wnt signaling pathway

PubMed Central

2014-01-01

The Wnt signaling pathway is an evolutionary conserved system, having pivotal roles during animal development. When over-activated, this signaling pathway is involved in cancer initiation and progression. The canonical Wnt pathway regulates the stability of β-catenin primarily by a destruction complex containing a number of different proteins, including Glycogen synthase kinase 3β (GSK-3β) and Axin, that promote proteasomal degradation of β-catenin. As this signaling cascade is modified by various proteins, novel screens aimed at identifying new Wnt signaling regulators were conducted in our laboratory. One of the different genes that were identified as Wnt signaling activators was Aldolase C (ALDOC). Here we report that ALDOC, Aldolase A (ALDOA) and Aldolase B (ALDOB) activate Wnt signaling in a GSK-3β-dependent mechanism, by disrupting the GSK-3β-Axin interaction and targeting Axin to the dishevelled (Dvl)-induced signalosomes that positively regulate the Wnt pathway thus placing the Aldolase proteins as novel Wnt signaling regulators. PMID:24993527
Occurrence of jasmonates during cystocarp development in the red alga Grateloupia imbricata.

PubMed

Pilar, Garcia-Jimenez; Olegario, Brito-Romano; Rafael, Robaina R

2016-12-01

In this study, we highlight the effects of methyl jasmonate (MeJa) on cystocarp development in the red macroscopic alga Grateloupia imbricata. In G. imbricata, jasmonate release is related to the reproductive state, as fertile thalli (i.e., those that have cystocarps) released significant amounts of this volatile compound (1.27 ± 0.20 mM · mg fw -1 · h -1 ) compared with infertile thalli (0.95 ± 0.12 mM · mg fw -1 · h -1 ). Treating G. imbricata thalli with MeJa revealed a significant increase in cystocarp number (1.5 ± 0.27 cystocarps · mm -2 ), which was ~7.5-fold greater than in untreated thalli (0.2 ± 0.07 cystocarps · mm -2 ). Maturation was completed within 48 h with MeJa treatment, a shortening of the typical >3-week maturation period, and included the opening of cystocarps and the presence of dehiscent cavities. Release rates of jasmonates after exogenous MeJa treatment were also modified based on the cystocarp maturation level. All of these effects were reduced in the presence of phenidone, which blocks MeJa production, indicating that the MeJa action is genuine. The effects of MeJa during cystocarp maturation were not replicated by derivatives of reactive oxygen species from the same jasmonic acid biosynthetic pathway, as the activities of scavenger enzymes and lipid peroxidation were unchanged between infertile and fertile thalli. Therefore, a reactive oxygen species-based mechanism is not involved during cystocarp development. We conclude that MeJa has an independent function as a growth regulator during G. imbricata reproduction. © 2016 Phycological Society of America.
Genetic Polymorphism in Extracellular Regulators of Wnt Signaling Pathway

PubMed Central

Sharma, Ashish Ranjan; Seo, Eun-Min; Nam, Ju-Suk

2015-01-01

The Wnt signaling pathway is mediated by a family of secreted glycoproteins through canonical and noncanonical mechanism. The signaling pathways are regulated by various modulators, which are classified into two classes on the basis of their interaction with either Wnt or its receptors. Secreted frizzled-related proteins (sFRPs) are the member of class that binds to Wnt protein and antagonizes Wnt signaling pathway. The other class consists of Dickkopf (DKK) proteins family that binds to Wnt receptor complex. The present review discusses the disease related association of various polymorphisms in Wnt signaling modulators. Furthermore, this review also highlights that some of the sFRPs and DKKs are unable to act as an antagonist for Wnt signaling pathway and thus their function needs to be explored more extensively. PMID:25945348
Wnt and the Wnt signaling pathway in bone development and disease

PubMed Central

Wang, Yiping; Li, Yi-Ping; Paulson, Christie; Shao, Jian-Zhong; Zhang, Xiaoling; Wu, Mengrui; Chen, Wei

2014-01-01

Wnt signaling affects both bone modeling, which occurs during development, and bone remodeling, which is a lifelong process involving tissue renewal. Wnt signals are especially known to affect the differentiation of osteoblasts. In this review, we summarize recent advances in understanding the mechanisms of Wnt signaling, which is divided into two major branches: the canonical pathway and the noncanonical pathway. The canonical pathway is also called the Wnt/β-catenin pathway. There are two major noncanonical pathways: the Wnt-planar cell polarity pathway (Wnt-PCP pathway) and the Wnt-calcium pathway (Wnt-Ca2+ pathway). This review also discusses how Wnt ligands, receptors, intracellular effectors, transcription factors, and antagonists affect both the bone modeling and bone remodeling processes. We also review the role of Wnt ligands, receptors, intracellular effectors, transcription factors, and antagonists in bone as demonstrated in mouse models. Disrupted Wnt signaling is linked to several bone diseases, including osteoporosis, van Buchem disease, and sclerosteosis. Studying the mechanism of Wnt signaling and its interactions with other signaling pathways in bone will provide potential therapeutic targets to treat these bone diseases. PMID:24389191
Silverleaf whitefly induces salicylic acid defenses and suppresses effectual jasmonic acid defenses.

PubMed

Zarate, Sonia I; Kempema, Louisa A; Walling, Linda L

2007-02-01

The basal defenses important in curtailing the development of the phloem-feeding silverleaf whitefly (Bemisia tabaci type B; SLWF) on Arabidopsis (Arabidopsis thaliana) were investigated. Sentinel defense gene RNAs were monitored in SLWF-infested and control plants. Salicylic acid (SA)-responsive gene transcripts accumulated locally (PR1, BGL2, PR5, SID2, EDS5, PAD4) and systemically (PR1, BGL2, PR5) during SLWF nymph feeding. In contrast, jasmonic acid (JA)- and ethylene-dependent RNAs (PDF1.2, VSP1, HEL, THI2.1, FAD3, ERS1, ERF1) were repressed or not modulated in SLWF-infested leaves. To test for a role of SA and JA pathways in basal defense, SLWF development on mutant and transgenic lines that constitutively activate or impair defense pathways was determined. By monitoring the percentage of SLWF nymphs in each instar, we show that mutants that activate SA defenses (cim10) or impair JA defenses (coi1) accelerated SLWF nymphal development. Reciprocally, mutants that activate JA defenses (cev1) or impair SA defenses (npr1, NahG) slowed SLWF nymphal development. Furthermore, when npr1 plants, which do not activate downstream SA defenses, were treated with methyl jasmonate, a dramatic delay in nymph development was observed. Collectively, these results showed that SLWF-repressed, JA-regulated defenses were associated with basal defense to the SLWF.
The effect of methyl jasmonate and light irradiation treatments on the stilbenoid biosynthetic pathway in Vitis vinifera cell suspension cultures.

PubMed

Andi, Seyed Ali; Gholami, Mansour; Ford, Christopher M

2018-04-01

Grape stilbenes are a well-known family of plant polyphenolics that have been confirmed to have many biological activities in relation to health benefits. In the present study, we investigated the effect of methyl jasmonate (MeJA) elicitor at four different concentrations (25, 50, 100 and 200 μM) in combination or not with high-level light irradiation (10,000 LUX) on a cell line obtained from the pulp of Vitis vinifera cv. Shahani. Our results showed that the stilbene synthesis pathway is inhibited by high-light conditions. A concentration of 50 μM MeJA was optimum for efficient production and high accumulation of total phenolics and total flavonoids as well as total stilbenoids. Furthermore, we showed that there is a significant negative correlation between the production of these metabolites and cell growth. These data provide valuable information for the future scale-up of cell cultures for the production of these very high value compounds in bioreactor system.
Emerging roles in plant defense for cis-jasmone-induced cytochrome P450 CYP81D11.

PubMed

Matthes, Michaela; Bruce, Toby; Chamberlain, Keith; Pickett, John; Napier, Johnathan

2011-04-01

cis-Jasmone is a volatile organic compound emitted constitutively by flowers or leaves of several plant species where it acts as an attractant for pollinators and as a chemical cue for host localisation (or avoidance) for insects. ( 1-3) It is also released by some plant species after feeding damage inflicted by herbivorous insects and in this case might serve as a chemical cue for parasitoids to guide them to their prey (so called "indirect defense"). ( 4,5) Moreover, we have recently shown that plants can perceive cis-jasmone and that it acts as a signaling molecule in A. thaliana, inducing a discrete and distinctive suite of genes, of which a large subset is putatively involved in metabolism and defense responses. ( 6) Cytochrome P450s feature prominently in these functional subsets and of these the highest fold change upon cis-jasmone treatment occurred with the cytochrome CYP81D11 (At3g28740). ( 6) Hence this gene was chosen for a more thorough analysis of the potential biological relevance of the cis-jasmone induced defense response. Although the precise function of CYP81D11 remains to be determined, we could previously demonstrate its involvement in the indirect defense response in Arabidopsis, as plants exposed to cis-jasmone ceased to be attractive to the aphid parasitoid Aphidius ervi when this P450 was inactivated by T-DNA insertion mutagenesis. ( 6) Here we report additional experiments which give further support to a role of CYP81D11 in the direct or indirect defense response of A. thaliana.
Premetazoan origin of the Hippo signaling pathway

PubMed Central

Sebé-Pedrós, Arnau; Zheng, Yonggang; Ruiz-Trillo, Iñaki; Pan, Duojia

2012-01-01

Summary Non-aggregative multicellularity requires strict control of cell number. The Hippo signaling pathway coordinates cell proliferation and apoptosis and is a central regulator of organ size in animals. Recent studies have shown the presence of key members of the Hippo pathway in non-bilaterian animals, but failed to identify this pathway outside Metazoa. Through comparative analyses of recently sequenced holozoan genomes, we show that Hippo pathway components, such as the kinases Hippo and Warts, the co-activator Yorkie and the transcription factor Scalloped, were already present in the unicellular ancestors of animals. Remarkably, functional analysis of Hippo components of the amoeboid holozoan Capsaspora owczarzaki, performed in Drosophila, demonstrate that the growth-regulatory activity of the Hippo pathway is conserved in this unicellular lineage. Our findings show that the Hippo pathway evolved well before the origin of Metazoa and highlight the importance of Hippo signaling as a key developmental mechanism pre-dating the origin of Metazoa. PMID:22832104
Frontier of Epilepsy Research - mTOR signaling pathway

PubMed Central

2011-01-01

Studies of epilepsy have mainly focused on the membrane proteins that control neuronal excitability. Recently, attention has been shifting to intracellular proteins and their interactions, signaling cascades and feedback regulation as they relate to epilepsy. The mTOR (mammalian target of rapamycin) signal transduction pathway, especially, has been suggested to play an important role in this regard. These pathways are involved in major physiological processes as well as in numerous pathological conditions. Here, involvement of the mTOR pathway in epilepsy will be reviewed by presenting; an overview of the pathway, a brief description of key signaling molecules, a summary of independent reports and possible implications of abnormalities of those molecules in epilepsy, a discussion of the lack of experimental data, and questions raised for the understanding its epileptogenic mechanism. PMID:21467839
The merged basins of signal transduction pathways in spatiotemporal cell biology.

PubMed

Hou, Yingchun; Hou, Yang; He, Siyu; Ma, Caixia; Sun, Mengyao; He, Huimin; Gao, Ning

2014-03-01

Numerous evidences have indicated that a signal system is composed by signal pathways, each pathway is composed by sub-pathways, and the sub-pathway is composed by the original signal terminals initiated with a protein/gene. We infer the terminal signals merged signal transduction system as "signal basin". In this article, we discussed the composition and regulation of signal basins, and the relationship between the signal basin control and triple W of spatiotemporal cell biology. Finally, we evaluated the importance of the systemic regulation to gene expression by signal basins under triple W. We hope our discussion will be the beginning to cause the attention for this area from the scientists of life science. © 2013 Wiley Periodicals, Inc.
Arabidopsis AGAMOUS Regulates Sepal Senescence by Driving Jasmonate Production

PubMed Central

Jibran, Rubina; Tahir, Jibran; Cooney, Janine; Hunter, Donald A.; Dijkwel, Paul P.

2017-01-01

The signal that initiates the age-regulated senescence program in flowers is still unknown. Here we propose for the ephemeral Arabidopsis thaliana flower that it dies because of continued expression of the MADS-box transcription factor AGAMOUS (AG). AG is necessary for specifying the reproductive structures of the flower. Flowers of ag-1, which lack AG, exhibited delayed sepal senescence and abscission. The flowers also had reduced jasmonic acid (JA) content. Other anther-defective sterile mutants deficient in JA, defective in anther dehiscence 1 (dad1) and delayed dehiscence 2 (dde2), exhibited delayed sepal senescence and abscission as well. Manually pollinated dad1 flowers produced siliques but still had delayed senescence, demonstrating that absence of pollination does not cause delayed senescence. When ag-1, dad1 and dde2 flowers were sprayed with 100 μM methyl jasmonate, the sepal senescence and abscission phenotypes were rescued, suggesting that JA has a role in these processes. Our study uncovers a novel role for AG in determining the timing of death of the flower it helps develop and highlights a role for JA in sepal senescence. PMID:29312374

The common molecular players in plant hormone crosstalk and signaling.

PubMed

Ohri, Puja; Bhardwaj, Renu; Bali, Shagun; Kaur, Ravinderjit; Jasrotia, Shivam; Khajuria, Anjali; Parihar, Ripu D

2015-01-01

Plant growth and development is under the control of mutual interactions among plant hormones. The five classical categories of plant hormones include auxins, cytokinins, gibberellins, abscisic acid and ethylene. Additionally, newer classes of plant hormones have been recognized like brassinosteroids, jasmonic acid, salicylic acid and polyamines. These hormones play significant roles in regulating the plant growth and development. Various receptors and key signaling components of these hormones have been studied and identified. At genetic level, crosstalk among the various plant hormones is found to be antagonistic or synergistic. In addition, components of signaling pathway of one plant hormone interact with the signaling components of other hormone. Thus, an attempt has been made to review the literature regarding the role of plant hormones in plant physiology and the common molecular players in their signaling and crosstalk.
AT1 receptor signaling pathways in the cardiovascular system.

PubMed

Kawai, Tatsuo; Forrester, Steven J; O'Brien, Shannon; Baggett, Ariele; Rizzo, Victor; Eguchi, Satoru

2017-11-01

The importance of the renin angiotensin aldosterone system in cardiovascular physiology and pathophysiology has been well described whereas the detailed molecular mechanisms remain elusive. The angiotensin II type 1 receptor (AT1 receptor) is one of the key players in the renin angiotensin aldosterone system. The AT1 receptor promotes various intracellular signaling pathways resulting in hypertension, endothelial dysfunction, vascular remodeling and end organ damage. Accumulating evidence shows the complex picture of AT1 receptor-mediated signaling; AT1 receptor-mediated heterotrimeric G protein-dependent signaling, transactivation of growth factor receptors, NADPH oxidase and ROS signaling, G protein-independent signaling, including the β-arrestin signals and interaction with several AT1 receptor interacting proteins. In addition, there is functional cross-talk between the AT1 receptor signaling pathway and other signaling pathways. In this review, we will summarize an up to date overview of essential AT1 receptor signaling events and their functional significances in the cardiovascular system. Copyright © 2017 Elsevier Ltd. All rights reserved.
Ethylene-Inhibited Jasmonic Acid Biosynthesis Promotes Mesocotyl/Coleoptile Elongation of Etiolated Rice Seedlings[OPEN

PubMed Central

Xiong, Qing; Ma, Biao; Lu, Xiang; Huang, Yi-Hua; He, Si-Jie; Yang, Chao; Yin, Cui-Cui; Zhou, Yang; Wang, Wen-Sheng; Li, Zhi-Kang; Chen, Shou-Yi

2017-01-01

Elongation of the mesocotyl and coleoptile facilitates the emergence of rice (Oryza sativa) seedlings from soil and is affected by various genetic and environment factors. The regulatory mechanism underlying this process remains largely unclear. Here, we examined the regulation of mesocotyl and coleoptile growth by characterizing a gaoyao1 (gy1) mutant that exhibits a longer mesocotyl and longer coleoptile than its original variety of rice. GY1 was identified through map-based cloning and encodes a PLA1-type phospholipase that localizes in chloroplasts. GY1 functions at the initial step of jasmonic acid (JA) biosynthesis to repress mesocotyl and coleoptile elongation in etiolated rice seedlings. Ethylene inhibits the expression of GY1 and other genes in the JA biosynthesis pathway to reduce JA levels and enhance mesocotyl and coleoptile growth by promoting cell elongation. Genetically, GY1 acts downstream of the OsEIN2-mediated ethylene signaling pathway to regulate mesocotyl/coleoptile growth. Through analysis of the resequencing data from 3000 rice accessions, we identified a single natural variation of the GY1 gene, GY1376T, which contributes to mesocotyl elongation in rice varieties. Our study reveals novel insights into the regulatory mechanism of mesocotyl/coleoptile elongation and should have practical applications in rice breeding programs. PMID:28465411
Transcriptome Profiling Reveals the Negative Regulation of Multiple Plant Hormone Signaling Pathways Elicited by Overexpression of C-Repeat Binding Factors.

PubMed

Li, Aixin; Zhou, Mingqi; Wei, Donghui; Chen, Hu; You, Chenjiang; Lin, Juan

2017-01-01

C-repeat binding factors (CBF) are a subfamily of AP2 transcription factors that play critical roles in the regulation of plant cold tolerance and growth in low temperature. In the present work, we sought to perform a detailed investigation into global transcriptional regulation of plant hormone signaling associated genes in transgenic plants engineered with CBF genes. RNA samples from Arabidopsis thaliana plants overexpressing two CBF genes, CBF2 and CBF3 , were subjected to Illumina HiSeq 2000 RNA sequencing (RNA-Seq). Our results showed that more than half of the hormone associated genes that were differentially expressed in CBF2 or CBF3 transgenic plants were related to auxin signal transduction and metabolism. Most of these alterations in gene expression could lead to repression of auxin signaling. Accordingly, the IAA content was significantly decreased in young tissues of plants overexpressing CBF2 and CBF3 compared with wild type. In addition, genes associated with the biosynthesis of Jasmonate (JA) and Salicylic acid (SA), as well as the signal sensing of Brassinolide (BR) and SA, were down-regulated, while genes associated with Gibberellin (GA) deactivation were up-regulated. In general, overexpression of CBF2 and CBF3 negatively affects multiple plant hormone signaling pathways in Arabidopsis . The transcriptome analysis using CBF2 and CBF3 transgenic plants provides novel and integrated insights into the interaction between CBFs and plant hormones, particularly the modulation of auxin signaling, which may contribute to the improvement of crop yields under abiotic stress via molecular engineering using CBF genes.
Transcriptome Profiling Reveals the Negative Regulation of Multiple Plant Hormone Signaling Pathways Elicited by Overexpression of C-Repeat Binding Factors

PubMed Central

Li, Aixin; Zhou, Mingqi; Wei, Donghui; Chen, Hu; You, Chenjiang; Lin, Juan

2017-01-01

C-repeat binding factors (CBF) are a subfamily of AP2 transcription factors that play critical roles in the regulation of plant cold tolerance and growth in low temperature. In the present work, we sought to perform a detailed investigation into global transcriptional regulation of plant hormone signaling associated genes in transgenic plants engineered with CBF genes. RNA samples from Arabidopsis thaliana plants overexpressing two CBF genes, CBF2 and CBF3, were subjected to Illumina HiSeq 2000 RNA sequencing (RNA-Seq). Our results showed that more than half of the hormone associated genes that were differentially expressed in CBF2 or CBF3 transgenic plants were related to auxin signal transduction and metabolism. Most of these alterations in gene expression could lead to repression of auxin signaling. Accordingly, the IAA content was significantly decreased in young tissues of plants overexpressing CBF2 and CBF3 compared with wild type. In addition, genes associated with the biosynthesis of Jasmonate (JA) and Salicylic acid (SA), as well as the signal sensing of Brassinolide (BR) and SA, were down-regulated, while genes associated with Gibberellin (GA) deactivation were up-regulated. In general, overexpression of CBF2 and CBF3 negatively affects multiple plant hormone signaling pathways in Arabidopsis. The transcriptome analysis using CBF2 and CBF3 transgenic plants provides novel and integrated insights into the interaction between CBFs and plant hormones, particularly the modulation of auxin signaling, which may contribute to the improvement of crop yields under abiotic stress via molecular engineering using CBF genes. PMID:28983312
Thiol-based redox proteins in abscisic acid and methyl jasmonate signaling in Brassica napus guard cells.

PubMed

Zhu, Mengmeng; Zhu, Ning; Song, Wen-yuan; Harmon, Alice C; Assmann, Sarah M; Chen, Sixue

2014-05-01

Reversibly oxidized cysteine sulfhydryl groups serve as redox sensors or targets of redox sensing that are important in various physiological processes. However, little is known about redox-sensitive proteins in guard cells and how they function in stomatal signaling. In this study, Brassica napus guard-cell proteins altered by redox in response to abscisic acid (ABA) or methyl jasmonate (MeJA) were identified by complementary proteomics approaches, saturation differential in-gel electrophoresis and isotope-coded affinity tagging. In total, 65 and 118 potential redox-responsive proteins were identified in ABA- and MeJA-treated guard cells, respectively. All the proteins contain at least one cysteine, and over half of them are predicted to form intra-molecular disulfide bonds. Most of the proteins fall into the functional groups of 'energy', 'stress and defense' and 'metabolism'. Based on the peptide sequences identified by mass spectrometry, 30 proteins were common to ABA- and MeJA-treated samples. A total of 44 cysteines were mapped in the identified proteins, and their levels of redox sensitivity were quantified. Two of the proteins, a sucrose non-fermenting 1-related protein kinase and an isopropylmalate dehydrogenase, were confirmed to be redox-regulated and involved in stomatal movement. This study creates an inventory of potential redox switches, and highlights a protein redox regulatory mechanism in ABA and MeJA signal transduction in guard cells. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.
Circadian Stress Regimes Affect the Circadian Clock and Cause Jasmonic Acid-Dependent Cell Death in Cytokinin-Deficient Arabidopsis Plants.

PubMed

Nitschke, Silvia; Cortleven, Anne; Iven, Tim; Feussner, Ivo; Havaux, Michel; Riefler, Michael; Schmülling, Thomas

2016-07-01

The circadian clock helps plants measure daylength and adapt to changes in the day-night rhythm. We found that changes in the light-dark regime triggered stress responses, eventually leading to cell death, in leaves of Arabidopsis thaliana plants with reduced cytokinin levels or defective cytokinin signaling. Prolonged light treatment followed by a dark period induced stress and cell death marker genes while reducing photosynthetic efficiency. This response, called circadian stress, is also characterized by altered expression of clock and clock output genes. In particular, this treatment strongly reduced the expression of CIRCADIAN CLOCK ASSOCIATED1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY). Intriguingly, similar changes in gene expression and cell death were observed in clock mutants lacking proper CCA1 and LHY function. Circadian stress caused strong changes in reactive oxygen species- and jasmonic acid (JA)-related gene expression. The activation of the JA pathway, involving the accumulation of JA metabolites, was crucial for the induction of cell death, since the cell death phenotype was strongly reduced in the jasmonate resistant1 mutant background. We propose that adaptation to circadian stress regimes requires a normal cytokinin status which, acting primarily through the AHK3 receptor, supports circadian clock function to guard against the detrimental effects of circadian stress. © 2016 American Society of Plant Biologists. All rights reserved.
Plant hormone jasmonate prioritizes defense over growth by interfering with gibberellin signaling cascade.

PubMed

Yang, Dong-Lei; Yao, Jian; Mei, Chuan-Sheng; Tong, Xiao-Hong; Zeng, Long-Jun; Li, Qun; Xiao, Lang-Tao; Sun, Tai-ping; Li, Jigang; Deng, Xing-Wang; Lee, Chin Mei; Thomashow, Michael F; Yang, Yinong; He, Zuhua; He, Sheng Yang

2012-05-08

Plants must effectively defend against biotic and abiotic stresses to survive in nature. However, this defense is costly and is often accompanied by significant growth inhibition. How plants coordinate the fluctuating growth-defense dynamics is not well understood and remains a fundamental question. Jasmonate (JA) and gibberellic acid (GA) are important plant hormones that mediate defense and growth, respectively. Binding of bioactive JA or GA ligands to cognate receptors leads to proteasome-dependent degradation of specific transcriptional repressors (the JAZ or DELLA family of proteins), which, at the resting state, represses cognate transcription factors involved in defense (e.g., MYCs) or growth [e.g. phytochrome interacting factors (PIFs)]. In this study, we found that the coi1 JA receptor mutants of rice (a domesticated monocot crop) and Arabidopsis (a model dicot plant) both exhibit hallmark phenotypes of GA-hypersensitive mutants. JA delays GA-mediated DELLA protein degradation, and the della mutant is less sensitive to JA for growth inhibition. Overexpression of a selected group of JAZ repressors in Arabidopsis plants partially phenocopies GA-associated phenotypes of the coi1 mutant, and JAZ9 inhibits RGA (a DELLA protein) interaction with transcription factor PIF3. Importantly, the pif quadruple (pifq) mutant no longer responds to JA-induced growth inhibition, and overexpression of PIF3 could partially overcome JA-induced growth inhibition. Thus, a molecular cascade involving the COI1-JAZ-DELLA-PIF signaling module, by which angiosperm plants prioritize JA-mediated defense over growth, has been elucidated.
Regulation of the Hippo signaling pathway by ubiquitin modification.

PubMed

Kim, Youngeun; Jho, Eek-Hoon

2018-03-01

The Hippo signaling pathway plays an essential role in adult tissue homeostasis and organ size control. Abnormal regulation of Hippo signaling can be a cause for multiple types of human cancers. Since the awareness of the importance of the Hippo signaling in a wide range of biological fields has been continually grown, it is also understood that a thorough and well-rounded comprehension of the precise dynamics could provide fundamental insights for therapeutic applications. Several components in the Hippo signaling pathway are known to be targeted for proteasomal degradation via ubiquitination by E3 ligases. β-TrCP is a well-known E3 ligase of YAP/TAZ, which leads to the reduction of YAP/TAZ levels. The Hippo signaling pathway can also be inhibited by the E3 ligases (such as ITCH) which target LATS1/2 for degradation. Regulation via ubiquitination involves not only complex network of E3 ligases but also deubiquitinating enzymes (DUBs), which remove ubiquitin from its targets. Interestingly, non-degradative ubiquitin modifications are also known to play important roles in the regulation of Hippo signaling. Although there has been much advanced progress in the investigation of ubiquitin modifications acting as regulators of the Hippo signaling pathway, research done to date still remains inadequate due to the sheer complexity and diversity of the subject. Herein, we review and discuss recent developments that implicate ubiquitin-mediated regulatory mechanisms at multiple steps of the Hippo signaling pathway. [BMB Reports 2018; 51(3): 143-150].
Jasmonic acid-mediated defense suppresses brassinosteroid-mediated susceptibility to Rice black streaked dwarf virus infection in rice.

PubMed

He, Yuqing; Zhang, Hehong; Sun, Zongtao; Li, Junmin; Hong, Gaojie; Zhu, Qisong; Zhou, Xuebiao; MacFarlane, Stuart; Yan, Fei; Chen, Jianping

2017-04-01

Plant hormones play a vital role in plant immune responses. However, in contrast to the relative wealth of information on hormone-mediated immunity in dicot plants, little information is available on monocot-virus defense systems. We used a high-throughput-sequencing approach to compare the global gene expression of Rice black-streaked dwarf virus (RBSDV)-infected rice plants with that of healthy plants. Exogenous hormone applications and transgenic rice were used to test RBSDV infectivity and pathogenicity. Our results revealed that the jasmonic acid (JA) pathway was induced while the brassinosteroid (BR) pathway was suppressed in infected plants. Foliar application of methyl jasmonate (MeJA) or brassinazole (BRZ) resulted in a significant reduction in RBSDV incidence, while epibrassinolide (BL) treatment increased RBSDV infection. Infection studies using coi1-13 and Go mutants demonstrated JA-mediated resistance and BR-mediated susceptibility to RBSDV infection. A mixture of MeJA and BL treatment resulted in a significant reduction in RBSDV infection compared with a single BL treatment. MeJA application efficiently suppressed the expression of BR pathway genes, and this inhibition depended on the JA coreceptor OsCOI1. Collectively, our results reveal that JA-mediated defense can suppress the BR-mediated susceptibility to RBSDV infection. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.
The Hippo-YAP signaling pathway and contact inhibition of growth

PubMed Central

Gumbiner, Barry M.; Kim, Nam-Gyun

2014-01-01

ABSTRACT The Hippo-YAP pathway mediates the control of cell proliferation by contact inhibition as well as other attributes of the physical state of cells in tissues. Several mechanisms sense the spatial and physical organization of cells, and function through distinct upstream modules to stimulate Hippo-YAP signaling: adherens junction or cadherin–catenin complexes, epithelial polarity and tight junction complexes, the FAT-Dachsous morphogen pathway, as well as cell shape, actomyosin or mechanotransduction. Soluble extracellular factors also regulate Hippo pathway signaling, often inhibiting its activity. Indeed, the Hippo pathway mediates a reciprocal relationship between contact inhibition and mitogenic signaling. As a result, cells at the edges of a colony, a wound in a tissue or a tumor are more sensitive to ambient levels of growth factors and more likely to proliferate, migrate or differentiate through a YAP and/or TAZ-dependent process. Thus, the Hippo-YAP pathway senses and responds to the physical organization of cells in tissues and coordinates these physical cues with classic growth-factor-mediated signaling pathways. This Commentary is focused on the biological significance of Hippo-YAP signaling and how upstream regulatory modules of the pathway interact to produce biological outcomes. PMID:24532814
Control of Carbon Assimilation and Partitioning by Jasmonate: An Accounting of Growth–Defense Tradeoffs

PubMed Central

Havko, Nathan E.; Major, Ian T.; Jewell, Jeremy B.; Attaran, Elham; Browse, John; Howe, Gregg A.

2016-01-01

Plant growth is often constrained by the limited availability of resources in the microenvironment. Despite the continuous threat of attack from insect herbivores and pathogens, investment in defense represents a lost opportunity to expand photosynthetic capacity in leaves and absorption of nutrients and water by roots. To mitigate the metabolic expenditure on defense, plants have evolved inducible defense strategies. The plant hormone jasmonate (JA) is a key regulator of many inducible defenses. Synthesis of JA in response to perceived danger leads to the deployment of a variety of defensive structures and compounds, along with a potent inhibition of growth. Genetic studies have established an important role for JA in mediating tradeoffs between growth and defense. However, several gaps remain in understanding of how JA signaling inhibits growth, either through direct transcriptional control of JA-response genes or crosstalk with other signaling pathways. Here, we highlight recent progress in uncovering the role of JA in controlling growth-defense balance and its relationship to resource acquisition and allocation. We also discuss tradeoffs in the context of the ability of JA to promote increased leaf mass per area (LMA), which is a key indicator of leaf construction costs and leaf life span. PMID:27135227
Targeting Notch signalling pathway of cancer stem cells.

PubMed

Venkatesh, Vandana; Nataraj, Raghu; Thangaraj, Gopenath S; Karthikeyan, Murugesan; Gnanasekaran, Ashok; Kaginelli, Shanmukhappa B; Kuppanna, Gobianand; Kallappa, Chandrashekrappa Gowdru; Basalingappa, Kanthesh M

2018-01-01

Cancer stem cells (CSCs) have been defined as cells within tumor that possess the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. CSCs have been increasingly identified in blood cancer, prostate, ovarian, lung, melanoma, pancreatic, colon, brain and many more malignancies. CSCs have slow growth rate and are resistant to chemotherapy and radiotherapy that lead to the failure of traditional current therapy. Eradicating the CSCs and recurrence, is promising aspect for the cure of cancer. The CSCs like any other stem cells activate the signal transduction pathways that involve the development and tissue homeostasis, which include Notch signaling pathway. The new treatment targets these pathway that control stem-cell replication, survival and differentiation that are under development. Notch inhibitors either single or in combination with chemotherapy drugs have been developed to treat cancer and its recurrence. This approach of targeting signaling pathway of CSCs represents a promising future direction for the therapeutic strategy to cure cancer.
A comprehensive pathway map of epidermal growth factor receptor signaling

PubMed Central

Oda, Kanae; Matsuoka, Yukiko; Funahashi, Akira; Kitano, Hiroaki

2005-01-01

The epidermal growth factor receptor (EGFR) signaling pathway is one of the most important pathways that regulate growth, survival, proliferation, and differentiation in mammalian cells. Reflecting this importance, it is one of the best-investigated signaling systems, both experimentally and computationally, and several computational models have been developed for dynamic analysis. A map of molecular interactions of the EGFR signaling system is a valuable resource for research in this area. In this paper, we present a comprehensive pathway map of EGFR signaling and other related pathways. The map reveals that the overall architecture of the pathway is a bow-tie (or hourglass) structure with several feedback loops. The map is created using CellDesigner software that enables us to graphically represent interactions using a well-defined and consistent graphical notation, and to store it in Systems Biology Markup Language (SBML). PMID:16729045
Interleukins and their signaling pathways in the Reactome biological pathway database.

PubMed

Jupe, Steve; Ray, Keith; Roca, Corina Duenas; Varusai, Thawfeek; Shamovsky, Veronica; Stein, Lincoln; D'Eustachio, Peter; Hermjakob, Henning

2018-04-01

much molecular detail as possible and are linked to literature citations that contain supporting experimental details. All newly created events undergo a peer-review process before they are added to the database and made available on the associated Web site. New content is added quarterly. The 63rd release of Reactome in December 2017 contains 10,996 human proteins participating in 11,426 events in 2,179 pathways. In addition, analytic tools allow data set submission for the identification and visualization of pathway enrichment and representation of expression profiles as an overlay on Reactome pathways. Protein-protein and compound-protein interactions from several sources, including custom user data sets, can be added to extend pathways. Pathway diagrams and analytic result displays can be downloaded as editable images, human-readable reports, and files in several standard formats that are suitable for computational reuse. Reactome content is available programmatically through a REpresentational State Transfer (REST)-based content service and as a Neo4J graph database. Signaling pathways for IL-1 to IL-38 are hierarchically classified within the pathway "signaling by interleukins." The classification used is largely derived from Akdis et al. The addition to Reactome of a complete set of the known human interleukins, their receptors, and established signaling pathways linked to annotations of relevant aspects of immune function provides a significant computationally accessible resource of information about this important family. This information can be extended easily as new discoveries become accepted as the consensus in the field. A key aim for the future is to increase coverage of gene expression changes induced by interleukin signaling. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
Jasmonic acid/methyl jasmonate accumulate in wounded soybean hypocotyls and modulate wound gene expression.

PubMed

Creelman, R A; Tierney, M L; Mullet, J E

1992-06-01

Jasmonic acid (JA) and its methyl ester, methyl jasmonate (MeJA), are plant lipid derivatives that resemble mammalian eicosanoids in structure and biosynthesis. These compounds are proposed to play a role in plant wound and pathogen responses. Here we report the quantitative determination of JA/MeJA in planta by a procedure based on the use of [13C,2H3]MeJA as an internal standard. Wounded soybean (Glycine max [L] Merr. cv. Williams) stems rapidly accumulated MeJA and JA. Addition of MeJA to soybean suspension cultures also increased mRNA levels for three wound-responsive genes (chalcone synthase, vegetative storage protein, and proline-rich cell wall protein) suggesting a role for MeJA/JA in the mediation of several changes in gene expression associated with the plants' response to wounding.
Modeling of cell signaling pathways in macrophages by semantic networks

PubMed Central

Hsing, Michael; Bellenson, Joel L; Shankey, Conor; Cherkasov, Artem

2004-01-01

Background Substantial amounts of data on cell signaling, metabolic, gene regulatory and other biological pathways have been accumulated in literature and electronic databases. Conventionally, this information is stored in the form of pathway diagrams and can be characterized as highly "compartmental" (i.e. individual pathways are not connected into more general networks). Current approaches for representing pathways are limited in their capacity to model molecular interactions in their spatial and temporal context. Moreover, the critical knowledge of cause-effect relationships among signaling events is not reflected by most conventional approaches for manipulating pathways. Results We have applied a semantic network (SN) approach to develop and implement a model for cell signaling pathways. The semantic model has mapped biological concepts to a set of semantic agents and relationships, and characterized cell signaling events and their participants in the hierarchical and spatial context. In particular, the available information on the behaviors and interactions of the PI3K enzyme family has been integrated into the SN environment and a cell signaling network in human macrophages has been constructed. A SN-application has been developed to manipulate the locations and the states of molecules and to observe their actions under different biological scenarios. The approach allowed qualitative simulation of cell signaling events involving PI3Ks and identified pathways of molecular interactions that led to known cellular responses as well as other potential responses during bacterial invasions in macrophages. Conclusions We concluded from our results that the semantic network is an effective method to model cell signaling pathways. The semantic model allows proper representation and integration of information on biological structures and their interactions at different levels. The reconstruction of the cell signaling network in the macrophage allowed detailed
Continuous exposure to the deterrents cis-jasmone and methyl jasmonate does not alter the behavioural responses of Frankliniella occidentalis.

PubMed

Egger, Barbara; Spangl, Bernhard; Koschier, Elisabeth Helene

2016-01-01

Behavioural responses of Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae), a generalist, cell sap-feeding insect species with piercing-sucking mouthparts, after continuous exposure to two deterrent secondary plant compounds are investigated. We compared in choice assays on bean leaf discs, the settling, feeding, and oviposition preferences of F. occidentalis females that had no experience with the two fatty acid derivatives methyl jasmonate and cis -jasmone before testing (naïve thrips) vs. females that had been exposed to the deterrent compounds before testing (experienced thrips). The thrips were exposed to the deterrents at low or high concentrations for varied time periods and subsequently tested on bean leaf discs treated with the respective deterrent at either a low or a high concentration. Frankliniella occidentalis females avoided settling on the deterrent-treated bean leaf discs for an observation period of 6 h, independent of their previous experience. Our results demonstrate that feeding and oviposition deterrence of the jasmonates to the thrips were not altered by continuous exposure of the thrips to the jasmonates. Habituation was not induced, neither by exposure to the low concentration of the deterrents nor by exposure to the high concentration. These results indicate that the risk of habituation to two volatile deterrent compounds after repeated exposure is not evident in F. occidentalis . This makes the two compounds potential candidates to be integrated in pest management strategies.
Wnt pathway in Dupuytren disease: connecting profibrotic signals.

PubMed

van Beuge, Marike M; Ten Dam, Evert-Jan P M; Werker, Paul M N; Bank, Ruud A

2015-12-01

A role of Wnt signaling in Dupuytren disease, a fibroproliferative disease of the hand and fingers, has not been fully elucidated. We examined a large set of Wnt pathway components and signaling targets and found significant dysregulation of 41 Wnt-related genes in tissue from the Dupuytren nodules compared with patient-matched control tissue. A large proportion of genes coding for Wnt proteins themselves was downregulated. However, both canonical Wnt targets and components of the noncanonical signaling pathway were upregulated. Immunohistochemical analysis revealed that protein expression of Wnt1-inducible secreted protein 1 (WISP1), a known Wnt target, was increased in nodules compared with control tissue, but knockdown of WISP1 using small interfering RNA (siRNA) in the Dupuytren myofibroblasts did not confirm a functional role. The protein expression of noncanonical pathway components Wnt5A and VANGL2 as well as noncanonical coreceptors Ror2 and Ryk was increased in nodules. On the contrary, the strongest downregulated genes in this study were 4 antagonists of Wnt signaling (DKK1, FRZB, SFRP1, and WIF1). Downregulation of these genes in the Dupuytren tissue was mimicked in vitro by treating normal fibroblasts with transforming growth factor β1 (TGF-β1), suggesting cross talk between different profibrotic pathways. Furthermore, siRNA-mediated knockdown of these antagonists in normal fibroblasts led to increased nuclear translocation of Wnt target β-catenin in response to TGF-β1 treatment. In conclusion, we have shown extensive dysregulation of Wnt signaling in affected tissue from Dupuytren disease patients. Components of both the canonical and the noncanonical pathways are upregulated, whereas endogenous antagonists are downregulated, possibly via interaction with other profibrotic pathways. Copyright © 2015 Elsevier Inc. All rights reserved.
Quantitative Biology of Exercise-Induced Signal Transduction Pathways.

PubMed

Liu, Timon Cheng-Yi; Liu, Gang; Hu, Shao-Juan; Zhu, Ling; Yang, Xiang-Bo; Zhang, Quan-Guang

2017-01-01

Exercise is essential in regulating energy metabolism. Exercise activates cellular, molecular, and biochemical pathways with regulatory roles in training response adaptation. Among them, endurance/strength training of an individual has been shown to activate its respective signal transduction pathways in skeletal muscle. This was further studied from the viewpoint of quantitative difference (QD). For the mean values, [Formula: see text], of two sets of data, their QD is defined as [Formula: see text] ([Formula: see text]). The function-specific homeostasis (FSH) of a function of a biosystem is a negative-feedback response of the biosystem to maintain the function-specific conditions inside the biosystem so that the function is perfectly performed. A function in/far from its FSH is called a normal/dysfunctional function. A cellular normal function can resist the activation of other signal transduction pathways so that there are normal function-specific signal transduction pathways which full activation maintains the normal function. An acute endurance/strength training may be dysfunctional, but its regular training may be normal. The normal endurance/strength training of an individual may resist the activation of other signal transduction pathways in skeletal muscle so that there may be normal endurance/strength training-specific signal transduction pathways (NEPs/NSPs) in skeletal muscle. The endurance/strength training may activate NSPs/NEPs, but the QD from the control is smaller than 0.80. The simultaneous activation of both NSPs and NEPs may enhance their respective activation, and the QD from the control is larger than 0.80. The low level laser irradiation pretreatment of rats may promote the activation of NSPs in endurance training skeletal muscle. There may be NEPs/NSPs in skeletal muscle trained by normal endurance/strength training.

The JAK-STAT signaling pathway: input and output integration.

PubMed

Murray, Peter J

2007-03-01

Universal and essential to cytokine receptor signaling, the JAK-STAT pathway is one of the best understood signal transduction cascades. Almost 40 cytokine receptors signal through combinations of four JAK and seven STAT family members, suggesting commonality across the JAK-STAT signaling system. Despite intense study, there remain substantial gaps in understanding how the cascades are activated and regulated. Using the examples of the IL-6 and IL-10 receptors, I will discuss how diverse outcomes in gene expression result from regulatory events that effect the JAK1-STAT3 pathway, common to both receptors. I also consider receptor preferences by different STATs and interpretive problems in the use of STAT-deficient cells and mice. Finally, I consider how the suppressor of cytokine signaling (SOCS) proteins regulate the quality and quantity of STAT signals from cytokine receptors. New data suggests that SOCS proteins introduce additional diversity into the JAK-STAT pathway by adjusting the output of activated STATs that alters downstream gene activation.
Salicylic and jasmonic acid pathways are necessary for defence against Dickeya solani as revealed by a novel method for Blackleg disease screening of in vitro grown potato.

PubMed

Burra, D D; Mühlenbock, P; Andreasson, E

2015-09-01

Potato is major crop ensuring food security in Europe, and blackleg disease is increasingly causing losses in yield and during storage. Recently, one blackleg pathogen, Dickeya solani has been shown to be spreading in Northern Europe that causes aggressive disease development. Currently, identification of tolerant commercial potato varieties has been unsuccessful; this is confounded by the complicated etiology of the disease and a strong environmental influence on disease development. There is currently a lack of efficient testing systems. Here, we describe a system for quantification of blackleg symptoms on shoots of sterile in vitro potato plants, which saves time and space compared to greenhouse and existing field assays. We found no evidence for differences in infection between the described in vitro-based screening method and existing greenhouse assays. This system facilitates efficient screening of blackleg disease response of potato plants independent of other microorganisms and variable environmental conditions. We therefore used the in vitro screening method to increase understanding of plant mechanisms involved in blackleg disease development by analysing disease response of hormone- related (salicylic and jasmonic acid) transgenic potato plants. We show that both jasmonic (JA) and salicylic (SA) acid pathways regulate tolerance to blackleg disease in potato, a result unlike previous findings in Arabidopsis defence response to necrotrophic bacteria. We confirm this by showing induction of a SA marker, pathogenesis-related protein 1 (StPR1), and a JA marker, lipoxygenase (StLOX), in Dickeya solani infected in vitro potato plants. We also observed that tubers of transgenic potato plants were more susceptible to soft rot compared to wild type, suggesting a role for SA and JA pathways in general tolerance to Dickeya. © 2015 German Botanical Society and The Royal Botanical Society of the Netherlands.
NetPath: a public resource of curated signal transduction pathways

PubMed Central

2010-01-01

We have developed NetPath as a resource of curated human signaling pathways. As an initial step, NetPath provides detailed maps of a number of immune signaling pathways, which include approximately 1,600 reactions annotated from the literature and more than 2,800 instances of transcriptionally regulated genes - all linked to over 5,500 published articles. We anticipate NetPath to become a consolidated resource for human signaling pathways that should enable systems biology approaches. PMID:20067622
Jasmonate-induced biosynthesis of andrographolide in Andrographis paniculata.

PubMed

Sharma, Shiv Narayan; Jha, Zenu; Sinha, Rakesh Kumar; Geda, Arvind Kumar

2015-02-01

Andrographolide is a prominent secondary metabolite found in Andrographis paniculata that exhibits enormous pharmacological effects. In spite of immense value, the normal biosynthesis of andrographolide results in low amount of the metabolite. To induce the biosynthesis of andrographolide, we attempted elicitor-induced activation of andrographolide biosynthesis in cell cultures of A. paniculata. This was carried out by using methyl jasmonate (MeJA) as an elicitor. Among the various concentrations of MeJA tested at different time periods, 5 µM MeJA yielded 5.25 times more andrographolide content after 24 h of treatment. The accumulation of andrographolide was correlated with the expression level of known regulatory genes (hmgs, hmgr, dxs, dxr, isph and ggps) of mevalonic acid (MVA) and 2-C-methyl-d-erythritol-4-phosphate (MEP) pathways. These results established the involvement of MeJA in andrographolide biosynthesis by inducing the transcription of its biosynthetic pathways genes. The coordination of isph, ggps and hmgs expression highly influenced the andrographolide biosynthesis. © 2014 Scandinavian Plant Physiology Society.
Modulation of ethylene- and heat-controlled hyponastic leaf movement in Arabidopsis thaliana by the plant defence hormones jasmonate and salicylate.

PubMed

van Zanten, Martijn; Ritsema, Tita; Polko, Joanna K; Leon-Reyes, Antonio; Voesenek, Laurentius A C J; Millenaar, Frank F; Pieterse, Corné M J; Peeters, Anton J M

2012-04-01

Upward leaf movement (hyponastic growth) is adopted by several plant species including Arabidopsis thaliana, as a mechanism to escape adverse growth conditions. Among the signals that trigger hyponastic growth are, the gaseous hormone ethylene, low light intensities, and supra-optimal temperatures (heat). Recent studies indicated that the defence-related phytohormones jasmonic acid (JA) and salicylic acid (SA) synthesized by the plant upon biotic infestation repress low light-induced hyponastic growth. The hyponastic growth response induced by high temperature (heat) treatment and upon application of the gaseous hormone ethylene is highly similar to the response induced by low light. To test if these environmental signals induce hyponastic growth via parallel pathways or converge downstream, we studied here the roles of Methyl-JA (MeJA) and SA on ethylene- and heat-induced hyponastic growth. For this, we used a time-lapse camera setup. Our study includes pharmacological application of MeJA and SA and biological infestation using the JA-inducing caterpillar Pieris rapae as well as mutants lacking JA or SA signalling components. The data demonstrate that MeJA is a positive, and SA, a negative regulator of ethylene-induced hyponastic growth and that both hormones repress the response to heat. Taking previous studies into account, we conclude that SA is the first among many tested components which is repressing hyponastic growth under all tested inductive environmental stimuli. However, since MeJA is a positive regulator of ethylene-induced hyponastic growth and is inhibiting low light- and heat-induced leaf movement, we conclude that defence hormones control hyponastic growth by affecting stimulus-specific signalling pathways.
Molecular Pathways: Translational and Therapeutic Implications of the Notch Signaling Pathway in Cancer

PubMed Central

Previs, Rebecca A.; Coleman, Robert L.; Harris, Adrian L.; Sood, Anil K.

2014-01-01

Over 100 years have passed since the first observation of the notched wing phenotype in Drosophila melanogaster, and significant progress has been made to characterize the role of the Notch receptor, its ligands, downstream targets, and crosstalk with other signaling pathways. The canonical Notch pathway with four Notch receptors (Notch1-4) and five ligands (DLL1, 3–4, Jagged 1–2) is an evolutionarily conserved cell signaling pathway that plays critical roles in cell-fate determination, differentiation, development, tissue patterning, cell proliferation, and death. In cancer, these roles have a critical impact on tumor behavior and response to therapy. Since the role of Notch remains tissue and context dependent, alterations within this pathway may lead to tumor suppressive or oncogenic phenotypes. Although no FDA approved therapies currently exist for the Notch pathway, multiple therapeutics (e.g., demcizumab, tarextumab, GSI MK0752, R04929097, and PF63084014) have been developed to target different aspects of this pathway for both hematologic and solid malignancies. Understanding the context-specific effects of the Notch pathway will be important for individualized therapies targeting this pathway. PMID:25388163
Elevated O3 increases volatile organic compounds via jasmonic acid pathway that promote the preference of parasitoid Encarsia formosa for tomato plants.

PubMed

Cui, Hongying; Wei, Jianing; Su, Jianwei; Li, Chuanyou; Ge, Feng

2016-12-01

The elevated atmospheric O 3 level may change the interactions of plants and insects, which potentially affects direct and indirect plant defences. However, the underlying mechanism of the impact of elevated O 3 on indirect plant defence, namely the efficacy of natural enemies, is unclear. Here we tested a hypothesis that linked the effects of elevated O 3 and whitefly herbivory on tomato volatile releases mediated by the jasmonic acid (JA) pathway with the preferences of parasitoid Encarsia formosa for two different tomato genotypes (wild-type (Wt) and JA-deficient genotype (spr2)). The O 3 and whitefly herbivory significantly increased the production of volatile organic compounds (VOCs), including monoterpenes and green leaf volatiles (GLVs). The Wt plants released higher volatile levels, particularly monoterpenes, than did the spr2 plants. In Y-tube tests, limonene and Z-3-hexanol played key roles in the attraction of E. formosa. Moreover, regardless of plant genotype, the two plant genotypes were preferred by adult E. formosa under the O 3 and O 3 + herbivory treatments. Our results suggest that under elevated O 3 , the activation of the JA pathway significantly up-regulates the emission rates of volatiles, through which the efficacy of natural enemy might be promoted. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Plastic Transcriptomes Stabilize Immunity to Pathogen Diversity: The Jasmonic Acid and Salicylic Acid Networks within the Arabidopsis/Botrytis Pathosystem.

PubMed

Zhang, Wei; Corwin, Jason A; Copeland, Daniel; Feusier, Julie; Eshbaugh, Robert; Chen, Fang; Atwell, Susana; Kliebenstein, Daniel J

2017-11-01

To respond to pathogen attack, selection and associated evolution has led to the creation of plant immune system that are a highly effective and inducible defense system. Central to this system are the plant defense hormones jasmonic acid (JA) and salicylic acid (SA) and crosstalk between the two, which may play an important role in defense responses to specific pathogens or even genotypes. Here, we used the Arabidopsis thaliana - Botrytis cinerea pathosystem to test how the host's defense system functions against genetic variation in a pathogen. We measured defense-related phenotypes and transcriptomic responses in Arabidopsis wild-type Col-0 and JA- and SA-signaling mutants, coi1-1 and npr1-1 , individually challenged with 96 diverse B. cinerea isolates. Those data showed genetic variation in the pathogen influences on all components within the plant defense system at the transcriptional level. We identified four gene coexpression networks and two vectors of defense variation triggered by genetic variation in B. cinerea This showed that the JA and SA signaling pathways functioned to constrain/canalize the range of virulence in the pathogen population, but the underlying transcriptomic response was highly plastic. These data showed that plants utilize major defense hormone pathways to buffer disease resistance, but not the metabolic or transcriptional responses to genetic variation within a pathogen. © 2017 American Society of Plant Biologists. All rights reserved.
Effect of methyl jasmonate on sugarbeet yield and storage properties

USDA-ARS?s Scientific Manuscript database

Methyl jasmonate is an endogenous plant hormone that induces plant defense mechanisms against environmental stresses and pathogens. Applied exogenously, methyl jasmonate has been shown to provide protection against a wide array of pathogens and environmental stresses in a variety of crop plants and ...
Jasmonic acid/methyl jasmonate accumulate in wounded soybean hypocotyls and modulate wound gene expression.

PubMed Central

Creelman, R A; Tierney, M L; Mullet, J E

1992-01-01

Jasmonic acid (JA) and its methyl ester, methyl jasmonate (MeJA), are plant lipid derivatives that resemble mammalian eicosanoids in structure and biosynthesis. These compounds are proposed to play a role in plant wound and pathogen responses. Here we report the quantitative determination of JA/MeJA in planta by a procedure based on the use of [13C,2H3]MeJA as an internal standard. Wounded soybean (Glycine max [L] Merr. cv. Williams) stems rapidly accumulated MeJA and JA. Addition of MeJA to soybean suspension cultures also increased mRNA levels for three wound-responsive genes (chalcone synthase, vegetative storage protein, and proline-rich cell wall protein) suggesting a role for MeJA/JA in the mediation of several changes in gene expression associated with the plants' response to wounding. Images PMID:1594598
Estradiol targets T cell signaling pathways in human systemic lupus.

PubMed

Walters, Emily; Rider, Virginia; Abdou, Nabih I; Greenwell, Cindy; Svojanovsky, Stan; Smith, Peter; Kimler, Bruce F

2009-12-01

The major risk factor for developing systemic lupus erythematosus (SLE) is being female. The present study utilized gene profiles of activated T cells from females with SLE and healthy controls to identify signaling pathways uniquely regulated by estradiol that could contribute to SLE pathogenesis. Selected downstream pathway genes (+/- estradiol) were measured by real time polymerase chain amplification. Estradiol uniquely upregulated six pathways in SLE T cells that control T cell function including interferon-alpha signaling. Measurement of interferon-alpha pathway target gene expression revealed significant differences (p= 0.043) in DRIP150 (+/- estradiol) in SLE T cell samples while IFIT1 expression was bimodal and correlated moderately (r= 0.55) with disease activity. The results indicate that estradiol alters signaling pathways in activated SLE T cells that control T cell function. Differential expression of transcriptional coactivators could influence estrogen-dependent gene regulation in T cell signaling and contribute to SLE onset and disease pathogenesis.
A lateral signalling pathway coordinates shape volatility during cell migration

PubMed Central

Zhang, Liang; Luga, Valbona; Armitage, Sarah K.; Musiol, Martin; Won, Amy; Yip, Christopher M.; Plotnikov, Sergey V.; Wrana, Jeffrey L.

2016-01-01

Cell migration is fundamental for both physiological and pathological processes. Migrating cells usually display high dynamics in morphology, which is orchestrated by an integrative array of signalling pathways. Here we identify a novel pathway, we term lateral signalling, comprised of the planar cell polarity (PCP) protein Pk1 and the RhoGAPs, Arhgap21/23. We show that the Pk1–Arhgap21/23 complex inhibits RhoA, is localized on the non-protrusive lateral membrane cortex and its disruption leads to the disorganization of the actomyosin network and altered focal adhesion dynamics. Pk1-mediated lateral signalling confines protrusive activity and is regulated by Smurf2, an E3 ubiquitin ligase in the PCP pathway. Furthermore, we demonstrate that dynamic interplay between lateral and protrusive signalling generates cyclical fluctuations in cell shape that we quantify here as shape volatility, which strongly correlates with migration speed. These studies uncover a previously unrecognized lateral signalling pathway that coordinates shape volatility during productive cell migration. PMID:27226243
Murine Polyomavirus Cell Surface Receptors Activate Distinct Signaling Pathways Required for Infection.

PubMed

O'Hara, Samantha D; Garcea, Robert L

2016-11-01

Virus binding to the cell surface triggers an array of host responses, including activation of specific signaling pathways that facilitate steps in virus entry. Using mouse polyomavirus (MuPyV), we identified host signaling pathways activated upon virus binding to mouse embryonic fibroblasts (MEFs). Pathways activated by MuPyV included the phosphatidylinositol 3-kinase (PI3K), FAK/SRC, and mitogen-activated protein kinase (MAPK) pathways. Gangliosides and α4-integrin are required receptors for MuPyV infection. MuPyV binding to both gangliosides and the α4-integrin receptors was required for activation of the PI3K pathway; however, either receptor interaction alone was sufficient for activation of the MAPK pathway. Using small-molecule inhibitors, we confirmed that the PI3K and FAK/SRC pathways were required for MuPyV infection, while the MAPK pathway was dispensable. Mechanistically, the PI3K pathway was required for MuPyV endocytosis, while the FAK/SRC pathway enabled trafficking of MuPyV along microtubules. Thus, MuPyV interactions with specific cell surface receptors facilitate activation of signaling pathways required for virus entry and trafficking. Understanding how different viruses manipulate cell signaling pathways through interactions with host receptors could lead to the identification of new therapeutic targets for viral infection. Virus binding to cell surface receptors initiates outside-in signaling that leads to virus endocytosis and subsequent virus trafficking. How different viruses manipulate cell signaling through interactions with host receptors remains unclear, and elucidation of the specific receptors and signaling pathways required for virus infection may lead to new therapeutic targets. In this study, we determined that gangliosides and α4-integrin mediate mouse polyomavirus (MuPyV) activation of host signaling pathways. Of these pathways, the PI3K and FAK/SRC pathways were required for MuPyV infection. Both the PI3K and FAK/SRC pathways
Jasmonate-responsive transcription factors regulating plant secondary metabolism.

PubMed

Zhou, Meiliang; Memelink, Johan

2016-01-01

Plants produce a large variety of secondary metabolites including alkaloids, glucosinolates, terpenoids and phenylpropanoids. These compounds play key roles in plant-environment interactions and many of them have pharmacological activity in humans. Jasmonates (JAs) are plant hormones which induce biosynthesis of many secondary metabolites. JAs-responsive transcription factors (TFs) that regulate the JAs-induced accumulation of secondary metabolites belong to different families including AP2/ERF, bHLH, MYB and WRKY. Here, we give an overview of the types and functions of TFs that have been identified in JAs-induced secondary metabolite biosynthesis, and highlight their similarities and differences in regulating various biosynthetic pathways. We review major recent developments regarding JAs-responsive TFs mediating secondary metabolite biosynthesis, and provide suggestions for further studies. Copyright © 2016 Elsevier Inc. All rights reserved.
Continuous exposure to the deterrents cis-jasmone and methyl jasmonate does not alter the behavioural responses of Frankliniella occidentalis

PubMed Central

Egger, Barbara; Spangl, Bernhard; Koschier, Elisabeth Helene

2016-01-01

Behavioural responses of Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae), a generalist, cell sap-feeding insect species with piercing-sucking mouthparts, after continuous exposure to two deterrent secondary plant compounds are investigated. We compared in choice assays on bean leaf discs, the settling, feeding, and oviposition preferences of F. occidentalis females that had no experience with the two fatty acid derivatives methyl jasmonate and cis-jasmone before testing (naïve thrips) vs. females that had been exposed to the deterrent compounds before testing (experienced thrips). The thrips were exposed to the deterrents at low or high concentrations for varied time periods and subsequently tested on bean leaf discs treated with the respective deterrent at either a low or a high concentration. Frankliniella occidentalis females avoided settling on the deterrent-treated bean leaf discs for an observation period of 6 h, independent of their previous experience. Our results demonstrate that feeding and oviposition deterrence of the jasmonates to the thrips were not altered by continuous exposure of the thrips to the jasmonates. Habituation was not induced, neither by exposure to the low concentration of the deterrents nor by exposure to the high concentration. These results indicate that the risk of habituation to two volatile deterrent compounds after repeated exposure is not evident in F. occidentalis. This makes the two compounds potential candidates to be integrated in pest management strategies. PMID:26726263
The epiphytic fungus Pseudozyma aphidis induces jasmonic acid- and salicylic acid/nonexpressor of PR1-independent local and systemic resistance.

PubMed

Buxdorf, Kobi; Rahat, Ido; Gafni, Aviva; Levy, Maggie

2013-04-01

Pseudozyma spp. are yeast-like fungi, classified in the Ustilaginales, which are mostly epiphytic or saprophytic and are not pathogenic to plants. Several Pseudozyma species have been reported to exhibit biological activity against powdery mildews. However, previous studies have reported that Pseudozyma aphidis, which can colonize plant surfaces, is not associated with the collapse of powdery mildew colonies. In this report, we describe a novel P. aphidis strain and study its interactions with its plant host and the plant pathogen Botrytis cinerea. This isolate was found to secrete extracellular metabolites that inhibit various fungal pathogens in vitro and significantly reduce B. cinerea infection in vivo. Moreover, P. aphidis sensitized Arabidopsis (Arabidopsis thaliana) plants' defense machinery via local and systemic induction of pathogenesis-related1 (PR1) and plant defensin1.2 (PDF1.2) expression. P. aphidis also reduced B. cinerea infection, locally and systemically, in Arabidopsis mutants impaired in jasmonic acid (JA) or salicylic acid (SA) signaling. Thus, in addition to direct inhibition, P. aphidis may inhibit B. cinerea infection via induced resistance in a manner independent of SA, JA, and Nonexpressor of PR1 (NPR1). P. aphidis primed the plant defense machinery and induced stronger activation of PDF1.2 after B. cinerea infection. Finally, P. aphidis fully or partially reconstituted PR1 and PDF1.2 expression in npr1-1 mutant and in plants with the SA hydroxylase NahG transgene, but not in a jasmonate resistant1-1 mutant, after B. cinerea infection, suggesting that P. aphidis can bypass the SA/NPR1, but not JA, pathway to activate PR genes. Thus, either partial gene activation is sufficient to induce resistance, or the resistance is not directed solely through PR1 and PDF1.2 but probably through other pathogen-resistance genes or pathways as well.
Basic helix-loop-helix transcription factors JASMONATE-ASSOCIATED MYC2-LIKE1 (JAM1), JAM2, and JAM3 are negative regulators of jasmonate responses in Arabidopsis.

PubMed

Sasaki-Sekimoto, Yuko; Jikumaru, Yusuke; Obayashi, Takeshi; Saito, Hikaru; Masuda, Shinji; Kamiya, Yuji; Ohta, Hiroyuki; Shirasu, Ken

2013-09-01

Jasmonates regulate transcriptional reprogramming during growth, development, and defense responses. Jasmonoyl-isoleucine, an amino acid conjugate of jasmonic acid (JA), is perceived by the protein complex composed of the F-box protein CORONATINE INSENSITIVE1 (COI1) and JASMONATE ZIM DOMAIN (JAZ) proteins, leading to the ubiquitin-dependent degradation of JAZ proteins. This activates basic helix-loop-helix-type MYC transcription factors to regulate JA-responsive genes. Here, we show that the expression of genes encoding other basic helix-loop-helix transcription factors, JASMONATE ASSOCIATED MYC2-LIKE1 (JAM1), JAM2, and JAM3, is positively regulated in a COI1- and MYC2-dependent manner in Arabidopsis (Arabidopsis thaliana). However, contrary to myc2, the jam1jam2jam3 triple mutant exhibited shorter roots when treated with methyl jasmonate (MJ), indicating enhanced responsiveness to JA. Our genome-wide expression analyses revealed that key jasmonate metabolic genes as well as a set of genes encoding transcription factors that regulate the JA-responsive metabolic genes are negatively regulated by JAMs after MJ treatment. Consistently, loss of JAM genes resulted in higher accumulation of anthocyanin in MJ-treated plants as well as higher accumulation of JA and 12-hydroxyjasmonic acid in wounded plants. These results show that JAMs negatively regulate the JA responses in a manner that is mostly antagonistic to MYC2.
Purinergic signaling pathways in endocrine system.

PubMed

Bjelobaba, Ivana; Janjic, Marija M; Stojilkovic, Stanko S

2015-09-01

Adenosine-5'-triphosphate is released by neuroendocrine, endocrine, and other cell types and acts as an extracellular agonist for ligand-gated P2X cationic channels and G protein-coupled P2Y receptors in numerous organs and tissues, including the endocrine system. The breakdown of ATP by ectonucleotidases not only terminates its extracellular messenger functions, but also provides a pathway for the generation of two additional agonists: adenosine 5'-diphosphate, acting via some P2Y receptors, and adenosine, a native agonist for G protein-coupled adenosine receptors, also expressed in the endocrine system. This article provides a review of purinergic signaling pathways in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. We attempted to summarize current knowledge of purinergic receptor subtypes expressed in the endocrine system, including their roles in intracellular signaling, hormone secretion, and other cell functions. We also briefly review the release mechanism for adenosine-5'-triphosphate by neuroendocrine, endocrine and surrounding cells, the enzymes involved in adenosine-5'-triphosphate hydrolysis to adenosine-5'-diphosphate and adenosine, and the relevance of this pathway for sequential activation of receptors and termination of signaling. Published by Elsevier B.V.
Purinergic Signaling Pathways in Endocrine System

PubMed Central

Bjelobaba, Ivana; Janjic, Marija M.; Stojilkovic, Stanko S.

2015-01-01

Adenosine-5′-triphosphate is released by neuroendocrine, endocrine, and other cell types and acts as an extracellular agonist for ligand-gated P2X cationic channels and G protein-coupled P2Y receptors in numerous organs and tissues, including the endocrine system. The breakdown of ATP by ectonucleotidases not only terminates its extracellular messenger functions, but also provides a pathway for the generation of two additional agonists: adenosine 5′-diphosphate, acting via some P2Y receptors, and adenosine, a native agonist for G protein-coupled adenosine receptors, also expressed in the endocrine system. This article provides a review of purinergic signaling pathways in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. We attempted to summarize current knowledge of purinergic receptor subtypes expressed in the endocrine system, including their roles in intracellular signaling, hormone secretion, and other cell functions. We also briefly review the release mechanism for adenosine-5′-triphosphate by neuroendocrine, endocrine and surrounding cells, the enzymes involved in adenosine-5′-triphosphate hydrolysis to adenosine-5′-diphosphate and adenosine, and the relevance of this pathway for sequential activation of receptors and termination of signaling. PMID:25960051
Intercellular signaling pathways active during intervertebral disc growth, differentiation, and aging.

PubMed

Dahia, Chitra Lekha; Mahoney, Eric J; Durrani, Atiq A; Wylie, Christopher

2009-03-01

Intervertebral discs at different postnatal ages were assessed for active intercellular signaling pathways. To generate a spatial and temporal map of the signaling pathways active in the postnatal intervertebral disc (IVD). The postnatal IVD is a complex structure, consisting of 3 histologically distinct components, the nucleus pulposus, fibrous anulus fibrosus, and endplate. These differentiate and grow during the first 9 weeks of age in the mouse. Identification of the major signaling pathways active during and after the growth and differentiation period will allow functional analysis using mouse genetics and identify targets for therapy for individual components of the disc. Antibodies specific for individual cell signaling pathways were used on cryostat sections of IVD at different postnatal ages to identify which components of the IVD were responding to major classes of intercellular signal, including sonic hedgehog, Wnt, TGFbeta, FGF, and BMPs. We present a spatial/temporal map of these signaling pathways during growth, differentiation, and aging of the disc. During growth and differentiation of the disc, its different components respond at different times to different intercellular signaling ligands. Most of these are dramatically downregulated at the end of disc growth.

Endogenous jasmonic and salicylic acids levels in the Cd-hyperaccumulator Noccaea (Thlaspi) praecox exposed to fungal infection and/or mechanical stress.

PubMed

Llugany, M; Martin, S R; Barceló, J; Poschenrieder, C

2013-08-01

Sensitivity to Erysiphe in Noccaea praecox with low metal supply is related to the failure in enhancing SA. Cadmium protects against fungal-infection by direct toxicity and/or enhanced fungal-induced JA signaling. Metal-based defense against biotic stress is an attractive hypothesis on evolutionary advantages of plant metal hyperaccumulation. Metals may compensate for a defect in biotic stress signaling in hyperaccumulators (metal-therapy) by either or both direct toxicity to pathogens and by metal-induced alternative signaling pathways. Jasmonic acid (JA) and salicylic acid (SA) are well-established components of stress signaling pathways. However, few studies evaluate the influence of metals on endogenous concentrations of these defense-related hormones. Even less data are available for metal hyperaccumulators. To further test the metal-therapy hypothesis we analyzed endogenous SA and JA concentrations in Noccaea praecox, a cadmium (Cd) hyperaccumulator. Plants treated or not with Cd, were exposed to mechanical wounding, expected to enhance JA signaling, and/or to infection by biotrophic fungus Erysiphe cruciferarum for triggering SA. JA and SA were analyzed in leaf extracts using LC-ESI(-)-MS/MS. Plants without Cd were more susceptible to fungal attack than plants receiving Cd. Cadmium alone tended to increase leaf SA but not JA. Either or both fungal attack and mechanical wounding decreased SA levels and enhanced JA in the Cd-rich leaves of plants exposed to Cd. High leaf Cd in N. praecox seems to hamper biotic-stress-induced SA, while triggering JA signaling in response to fungal attack and wounding. To the best of our knowledge, this is the first report on the endogenous JA and SA levels in a Cd-hyperaccumulator exposed to different biotic and abiotic stresses. Our results support the view of a defect in SA stress signaling in Cd hyperaccumulating N. praecox.
Pharmacology of intracellular signalling pathways

PubMed Central

Nahorski, Stefan R

2006-01-01

This article provides a brief and somewhat personalized review of the dramatic developments that have occurred over the last 45 years in our understanding of intracellular signalling pathways associated with G-protein-coupled receptor activation. Signalling via cyclic AMP, the phosphoinositides and Ca2+ is emphasized and these systems have already been revealed as new pharmacological targets. The therapeutic benefits of most of such targets are, however, yet to be realized, but it is certain that the discipline of pharmacology needs to widen its boundaries to meet these challenges in the future. PMID:16402119
A novel class I Chitinase from Hippophae rhamnoides: Indications for participating in ICE-CBF cold stress signaling pathway.

PubMed

Kashyap, Prakriti; Deswal, Renu

2017-06-01

Plant chitinases are the members of PR (Pathogenesis related) proteins family and protect plants from biotic and abiotic stress. A novel chitinase HrCHI1 (Accession number JQ289153) of 954bp ORF encoding 317 amino acids protein was cloned, expressed and characterized from seabuckthorn, a cold/freeze tolerant shrub. The 3D structure (predicted with I-TASSER server) showed highest homology with Oryza sativa class I chitinase (PDB 2dkvA). Putative promoter region (obtained by genome walking) showed GCC box, E-boxes, the binding site for bHLH proteins and DRE elements, the CBF (C-repeat binding factor) binding site besides TATA and CAAT boxes. The gel shift assay with the nuclear extract indicated that the HrCHI1 might be participating in CBF/ERF dependent cold stress signaling pathway. The quantitative transcript profiling supported this observation as cold induced expression of HrCBF peaked earlier (at 1h) while HrCHI1 peaked latter (after 3h) indicating HrCHI1 expression might be induced by HrCBF. Further, HrCHI1 expression was methyl jasmonate (MeJa) dependent and salicylic acid (SA) independent. HrCHI1 was expressed in E. coli and purified using chitin affinity chromatography. It showed 512U/mg chitinase hydrolytic activity and resolved as a 34kDa spot with a slightly basic pI (8.5) on a 2-D gel. The E. coli cells containing recombinant chitinase showed higher rate of growth in cold in comparison with the cells containing the empty vector. In conclusion, we have isolated and characterized a cold responsive basic class I chitinase which is regulated by MeJa and seems to be functioning via CBF/ERF dependent cold stress signaling pathway. Copyright © 2017 Elsevier B.V. All rights reserved.
Plastic Transcriptomes Stabilize Immunity to Pathogen Diversity: The Jasmonic Acid and Salicylic Acid Networks within the Arabidopsis/Botrytis Pathosystem[OPEN

PubMed Central

Eshbaugh, Robert; Chen, Fang; Atwell, Susana

2017-01-01

To respond to pathogen attack, selection and associated evolution has led to the creation of plant immune system that are a highly effective and inducible defense system. Central to this system are the plant defense hormones jasmonic acid (JA) and salicylic acid (SA) and crosstalk between the two, which may play an important role in defense responses to specific pathogens or even genotypes. Here, we used the Arabidopsis thaliana-Botrytis cinerea pathosystem to test how the host’s defense system functions against genetic variation in a pathogen. We measured defense-related phenotypes and transcriptomic responses in Arabidopsis wild-type Col-0 and JA- and SA-signaling mutants, coi1-1 and npr1-1, individually challenged with 96 diverse B. cinerea isolates. Those data showed genetic variation in the pathogen influences on all components within the plant defense system at the transcriptional level. We identified four gene coexpression networks and two vectors of defense variation triggered by genetic variation in B. cinerea. This showed that the JA and SA signaling pathways functioned to constrain/canalize the range of virulence in the pathogen population, but the underlying transcriptomic response was highly plastic. These data showed that plants utilize major defense hormone pathways to buffer disease resistance, but not the metabolic or transcriptional responses to genetic variation within a pathogen. PMID:29042403
Obesity-Induced Hypertension: Brain Signaling Pathways

PubMed Central

da Silva, Alexandre A.; Wang, Zhen; Fang, Taolin; Aberdein, Nicola; de Lara Rodriguez, Cecilia E. P.; Hall, John E.

2017-01-01

Obesity greatly increases the risk for cardiovascular, metabolic, and renal diseases and is one of the most significant and preventable causes of increased blood pressure (BP) in patients with essential hypertension. This review high-lights recent advances in our understanding of central nervous system (CNS) signaling pathways that contribute to the etiology and pathogenesis of obesity-induced hypertension. We discuss the role of excess adiposity and activation of the brain leptin-melanocortin system in causing increased sympathetic activity in obesity. In addition, we highlight other potential brain mechanisms by which increased weight gain modulates metabolic and cardiovascular functions. Unraveling the CNS mechanisms responsible for increased sympathetic activation and hypertension and how circulating hormones activate brain signaling pathways to control BP offer potentially important therapeutic targets for obesity and hypertension. PMID:27262997
The expression pattern of the Picea glauca Defensin 1 promoter is maintained in Arabidopsis thaliana, indicating the conservation of signalling pathways between angiosperms and gymnosperms.

PubMed

Germain, Hugo; Lachance, Denis; Pelletier, Gervais; Fossdal, Carl Gunnar; Solheim, Halvor; Séguin, Armand

2012-01-01

A 1149 bp genomic fragment corresponding to the 5' non-coding region of the PgD1 (Picea glauca Defensin 1) gene was cloned, characterized, and compared with all Arabidopsis thaliana defensin promoters. The cloned fragment was found to contain several motifs specific to defence or hormonal response, including a motif involved in the methyl jasmonate reponse, a fungal elicitor responsive element, and TC-rich repeat cis-acting element involved in defence and stress responsiveness. A functional analysis of the PgD1 promoter was performed using the uidA (GUS) reporter system in stably transformed Arabidopsis and white spruce plants. The PgD1 promoter was responsive to jasmonic acid (JA), to infection by fungus and to wounding. In transgenic spruce embryos, GUS staining was clearly restricted to the shoot apical meristem. In Arabidopsis, faint GUS coloration was observed in leaves and flowers and a strong blue colour was observed in guard cells and trichomes. Transgenic Arabidopsis plants expressing the PgD1::GUS construct were also infiltrated with the hemibiotrophic pathogen Pseudomonas syringae pv. tomato DC3000. It caused a suppression of defensin expression probably resulting from the antagonistic relationship between the pathogen-stimulated salicylic acid pathway and the jasmonic acid pathway. It is therefore concluded that the PgD1 promoter fragment cloned appears to contain most if not all the elements for proper PgD1 expression and that these elements are also recognized in Arabidopsis despite the phylogenetic and evolutionary differences that separates them.
Jasmonate Hormone: Regulating Synthesis of Reduced Carbon Compounds in Plants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Browse, John

Our original interest in understanding the role of jasmonate (JA) in regulating the final stages of stamen and pollen development led to our discovery of the JAZ repressors, and the molecular mechanism of JA action is now a second important focus of our research. The specific goals for this grant period are to: 1. Investigate the generation and clearance of the hormone with emphasis on the regulation of the OPR3 enzyme and the hydrolysis of JA-Ile. 2. Use dominant-negative and overexpression constructs to explore the role of the MYC5 transcription factor in initiating and regulating JA responses. 3. Investigate specificmore » JAZ protein interactions that will help us to recognize and understand the extended network of processes, such as sulfur nutrition, that interface with JA signaling. The COI1 F-Box protein is a JA-Ile coreceptor and coi1 mutant plants lack JA responses. We have tested the possibility that sites of JA action can be probed by using tissue-specific promoters to drive expression of a COI1-YFP fusion protein in coi1 mutant plants deficient in stamen and pollen function. When we expressed COI1 behind a filament-specific promoter (from the DAD1 gene), filament elongation was restored but not anther dehiscence or pollen function. Three tapetum specific promoters, all failed to restore any of these three functions but, unexpectedly, a promoter active in the stomium and epidermal cells, restored both pollen function and anther dehiscence. Most importantly, our results demonstrate the power of promoter::COI1-YFP constructs in revealing the primary sites of JA-regulated gene expression that control developmental and other responses in neighboring tissues. We now plan to use this new tool to test current hypotheses about JA action in other organs of the plant. The MYC2, MYC3, and MYC4 proteins are the primary transcription factors initiating defense and root growth responses to JA signaling. However, transgenic plants overexpressing these proteins do not
The Wnt signaling pathway in familial exudative vitreoretinopathy and Norrie disease.

PubMed

Warden, Scott M; Andreoli, Christopher M; Mukai, Shizuo

2007-01-01

The Wnt signaling pathway is highly conserved among species and has an important role in many cell biological processes throughout the body. This signaling cascade is involved in regulating ocular growth and development, and recent findings indicate that this is particularly true in the retina. Mutations involving different aspects of the Wnt signaling pathway are being linked to several diseases of retinal development. The aim of this article is to first review the Wnt signaling pathway. We will then describe two conditions, familial exudative vitreoretinopathy (FEVR) and Norrie disease (ND), which have been shown to be caused in part by defects in the Wnt signaling cascade.
Genome-wide characterization of JASMONATE-ZIM DOMAIN transcription repressors in wheat (Triticum aestivum L.).

PubMed

Wang, Yukun; Qiao, Linyi; Bai, Jianfang; Wang, Peng; Duan, Wenjing; Yuan, Shaohua; Yuan, Guoliang; Zhang, Fengting; Zhang, Liping; Zhao, Changping

2017-02-13

The JASMONATE-ZIM DOMAIN (JAZ) repressor family proteins are jasmonate co-receptors and transcriptional repressor in jasmonic acid (JA) signaling pathway, and they play important roles in regulating the growth and development of plants. Recently, more and more researches on JAZ gene family are reported in many plants. Although the genome sequencing of common wheat (Triticum aestivum L.) and its relatives is complete, our knowledge about this gene family remains vacant. Fourteen JAZ genes were identified in the wheat genome. Structural analysis revealed that the TaJAZ proteins in wheat were as conserved as those in other plants, but had structural characteristics. By phylogenetic analysis, all JAZ proteins from wheat and other plants were clustered into 11 sub-groups (G1-G11), and TaJAZ proteins shared a high degree of similarity with some JAZ proteins from Aegliops tauschii, Brachypodium distachyon and Oryza sativa. The Ka/Ks ratios of TaJAZ genes ranged from 0.0016 to 0.6973, suggesting that the TaJAZ family had undergone purifying selection in wheat. Gene expression patterns obtained by quantitative real-time PCR (qRT-PCR) revealed differential temporal and spatial regulation of TaJAZ genes under multifarious abiotic stress treatments of high salinity, drought, cold and phytohormone. Among these, TaJAZ7, 8 and 12 were specifically expressed in the anther tissues of the thermosensitive genic male sterile (TGMS) wheat line BS366 and normal control wheat line Jing411. Compared with the gene expression patterns in the normal wheat line Jing411, TaJAZ7, 8 and 12 had different expression patterns in abnormally dehiscent anthers of BS366 at the heading stage 6, suggesting that specific up- or down-regulation of these genes might be associated with the abnormal anther dehiscence in TGMS wheat line. This study analyzed the size and composition of the JAZ gene family in wheat, and investigated stress responsive and differential tissue-specific expression profiles of each
Silverleaf Whitefly Induces Salicylic Acid Defenses and Suppresses Effectual Jasmonic Acid Defenses1[W][OA

PubMed Central

Zarate, Sonia I.; Kempema, Louisa A.; Walling, Linda L.

2007-01-01

The basal defenses important in curtailing the development of the phloem-feeding silverleaf whitefly (Bemisia tabaci type B; SLWF) on Arabidopsis (Arabidopsis thaliana) were investigated. Sentinel defense gene RNAs were monitored in SLWF-infested and control plants. Salicylic acid (SA)-responsive gene transcripts accumulated locally (PR1, BGL2, PR5, SID2, EDS5, PAD4) and systemically (PR1, BGL2, PR5) during SLWF nymph feeding. In contrast, jasmonic acid (JA)- and ethylene-dependent RNAs (PDF1.2, VSP1, HEL, THI2.1, FAD3, ERS1, ERF1) were repressed or not modulated in SLWF-infested leaves. To test for a role of SA and JA pathways in basal defense, SLWF development on mutant and transgenic lines that constitutively activate or impair defense pathways was determined. By monitoring the percentage of SLWF nymphs in each instar, we show that mutants that activate SA defenses (cim10) or impair JA defenses (coi1) accelerated SLWF nymphal development. Reciprocally, mutants that activate JA defenses (cev1) or impair SA defenses (npr1, NahG) slowed SLWF nymphal development. Furthermore, when npr1 plants, which do not activate downstream SA defenses, were treated with methyl jasmonate, a dramatic delay in nymph development was observed. Collectively, these results showed that SLWF-repressed, JA-regulated defenses were associated with basal defense to the SLWF. PMID:17189328
How Hippo Signaling Pathway Modulates Cardiovascular Development and Diseases.

PubMed

Zhou, Wenyi; Zhao, Mingyi

2018-01-01

Cardiovascular disease remains the leading cause of death around the globe. Cardiac deterioration is associated with irreversible cardiomyocyte loss. Understanding how the cardiovascular system develops and the pathological processes of cardiac disease will contribute to finding novel and preventive therapeutic methods. The canonical Hippo tumor suppressor pathway in mammalian cells is primarily composed of the MST1/2-SAV1-LATS1/2-MOB1-YAP/TAZ cascade. Continuing research on this pathway has identified other factors like RASSF1A, Nf2, MAP4Ks, and NDR1/2, further enriching our knowledge of the Hippo-YAP pathway. YAP, the core effecter of the Hippo pathway, may accumulate in the nucleus and initiate transcriptional activity if the pathway is inhibited. The role of Hippo signaling has been widely investigated in organ development and cancers. A heart of normal size and function which is critical for survival could not be generated without the proper regulation of the Hippo tumor suppressor pathway. Recent research has demonstrated a novel role of Hippo signaling in cardiovascular disease in the context of development, hypertrophy, angiogenesis, regeneration, apoptosis, and autophagy. In this review, we summarize the current knowledge of how Hippo signaling modulates pathological processes in cardiovascular disease and discuss potential molecular therapeutic targets.
Oncogenic Signaling Pathways in The Cancer Genome Atlas.

PubMed

Sanchez-Vega, Francisco; Mina, Marco; Armenia, Joshua; Chatila, Walid K; Luna, Augustin; La, Konnor C; Dimitriadoy, Sofia; Liu, David L; Kantheti, Havish S; Saghafinia, Sadegh; Chakravarty, Debyani; Daian, Foysal; Gao, Qingsong; Bailey, Matthew H; Liang, Wen-Wei; Foltz, Steven M; Shmulevich, Ilya; Ding, Li; Heins, Zachary; Ochoa, Angelica; Gross, Benjamin; Gao, Jianjiong; Zhang, Hongxin; Kundra, Ritika; Kandoth, Cyriac; Bahceci, Istemi; Dervishi, Leonard; Dogrusoz, Ugur; Zhou, Wanding; Shen, Hui; Laird, Peter W; Way, Gregory P; Greene, Casey S; Liang, Han; Xiao, Yonghong; Wang, Chen; Iavarone, Antonio; Berger, Alice H; Bivona, Trever G; Lazar, Alexander J; Hammer, Gary D; Giordano, Thomas; Kwong, Lawrence N; McArthur, Grant; Huang, Chenfei; Tward, Aaron D; Frederick, Mitchell J; McCormick, Frank; Meyerson, Matthew; Van Allen, Eliezer M; Cherniack, Andrew D; Ciriello, Giovanni; Sander, Chris; Schultz, Nikolaus

2018-04-05

Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFβ signaling, p53 and β-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these pathways, and 57% percent of tumors had at least one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy. Copyright © 2018. Published by Elsevier Inc.
Genome-wide identification of jasmonate biosynthetic genes and their characterization of their expression profiles during apple (Malus x domestica) fruit maturation

USDA-ARS?s Scientific Manuscript database

The plant hormones regulate many physiological processes including apple fruit ripening by integrating diverse developmental cues and environmental signals. In addition to the well-characterized role of ethylene, jasmonic acid (JA) and its derivatives have also been suggested to play an important ro...
Colored Petri net modeling and simulation of signal transduction pathways.

PubMed

Lee, Dong-Yup; Zimmer, Ralf; Lee, Sang Yup; Park, Sunwon

2006-03-01

Presented herein is a methodology for quantitatively analyzing the complex signaling network by resorting to colored Petri nets (CPN). The mathematical as well as Petri net models for two basic reaction types were established, followed by the extension to a large signal transduction system stimulated by epidermal growth factor (EGF) in an application study. The CPN models based on the Petri net representation and the conservation and kinetic equations were used to examine the dynamic behavior of the EGF signaling pathway. The usefulness of Petri nets is demonstrated for the quantitative analysis of the signal transduction pathway. Moreover, the trade-offs between modeling capability and simulation efficiency of this pathway are explored, suggesting that the Petri net model can be invaluable in the initial stage of building a dynamic model.
Signalling Network Construction for Modelling Plant Defence Response

PubMed Central

Miljkovic, Dragana; Stare, Tjaša; Mozetič, Igor; Podpečan, Vid; Petek, Marko; Witek, Kamil; Dermastia, Marina; Lavrač, Nada; Gruden, Kristina

2012-01-01

Plant defence signalling response against various pathogens, including viruses, is a complex phenomenon. In resistant interaction a plant cell perceives the pathogen signal, transduces it within the cell and performs a reprogramming of the cell metabolism leading to the pathogen replication arrest. This work focuses on signalling pathways crucial for the plant defence response, i.e., the salicylic acid, jasmonic acid and ethylene signal transduction pathways, in the Arabidopsis thaliana model plant. The initial signalling network topology was constructed manually by defining the representation formalism, encoding the information from public databases and literature, and composing a pathway diagram. The manually constructed network structure consists of 175 components and 387 reactions. In order to complement the network topology with possibly missing relations, a new approach to automated information extraction from biological literature was developed. This approach, named Bio3graph, allows for automated extraction of biological relations from the literature, resulting in a set of (component1, reaction, component2) triplets and composing a graph structure which can be visualised, compared to the manually constructed topology and examined by the experts. Using a plant defence response vocabulary of components and reaction types, Bio3graph was applied to a set of 9,586 relevant full text articles, resulting in 137 newly detected reactions between the components. Finally, the manually constructed topology and the new reactions were merged to form a network structure consisting of 175 components and 524 reactions. The resulting pathway diagram of plant defence signalling represents a valuable source for further computational modelling and interpretation of omics data. The developed Bio3graph approach, implemented as an executable language processing and graph visualisation workflow, is publically available at http://ropot.ijs.si/bio3graph/and can be utilised for
Effect of methyl jasmonate application to grapevine leaves on grape amino acid content.

PubMed

Garde-Cerdán, Teresa; Portu, Javier; López, Rosa; Santamaría, Pilar

2016-07-15

Over the last few years, considerable attention has been paid to the application of elicitors to vineyard. However, research about the effect of elicitors on grape amino acid content is scarce. Therefore, the aim of this study was to evaluate the influence of foliar application of methyl jasmonate on must amino acid content. Results revealed that total amino acid content was not modified by the application of methyl jasmonate. However, the individual content of certain amino acids was increased as consequence of methyl jasmonate foliar application, i.e., histidine, serine, tryptophan, phenylalanine, tyrosine, asparagine, methionine, and lysine. Among them, phenylalanine content was considerably increased; this amino acid is precursor of phenolic and aromatic compounds. In conclusion, foliar application of methyl jasmonate improved must nitrogen composition. This finding suggests that methyl jasmonate treatment might be conducive to obtain wines of higher quality since must amino acid composition could affect the wine volatile composition and the fermentation kinetics. Copyright © 2016 Elsevier Ltd. All rights reserved.
The Hippo signaling pathway in stem cell biology and cancer

PubMed Central

Mo, Jung-Soon; Park, Hyun Woo; Guan, Kun-Liang

2014-01-01

The Hippo signaling pathway, consisting of a highly conserved kinase cascade (MST and Lats) and downstream transcription coactivators (YAP and TAZ), plays a key role in tissue homeostasis and organ size control by regulating tissue-specific stem cells. Moreover, this pathway plays a prominent role in tissue repair and regeneration. Dysregulation of the Hippo pathway is associated with cancer development. Recent studies have revealed a complex network of upstream inputs, including cell density, mechanical sensation, and G-protein-coupled receptor (GPCR) signaling, that modulate Hippo pathway activity. This review focuses on the role of the Hippo pathway in stem cell biology and its potential implications in tissue homeostasis and cancer. PMID:24825474
Epidermal jasmonate perception is sufficient for all aspects of jasmonate-mediated male fertility in Arabidopsis.

PubMed

Jewell, Jeremy B; Browse, John

2016-03-01

Jasmonate (JA) signaling is essential for several environmental responses and reproductive development in many plant species. In Arabidopsis thaliana, the most obvious phenotype of JA biosynthetic and perception mutants is profound sporophytic male sterility characterized by failure of stamen filament elongation, severe delay of anther dehiscence and pollen inviability. The site of action of JA in the context of reproductive development has been discussed, but the ideas have not been tested experimentally. To this end we used targeted expression of a COI1-YFP transgene in the coi1-1 mutant background. As COI1 is an essential component of the JA co-receptor complex, the null coi1-1 mutant is male sterile due to lack of JA perception. We show that expression of COI1-YFP in the epidermis of the stamen filament and anther in coi1 mutant plants is sufficient to rescue filament elongation, anther dehiscence and pollen viability. In contrast, filament expression alone or expression in the tapetum do not restore dehiscence and pollen viability. These results demonstrate that epidermal JA perception is sufficient for anther function and pollen viability, and suggest the presence of a JA-dependent non-autonomous signal produced in the anther epidermis to synchronize both anther dehiscence and pollen maturation. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.
Optimization of a cAMP response element signal pathway reporter system.

PubMed

Shan, Qiang; Storm, Daniel R

2010-08-15

A sensitive cAMP response element (CRE) reporter system is essential for studying the cAMP/protein kinase A/cAMP response element binding protein signal pathway. Here we have tested a few CRE promoters and found one with high sensitivity to external stimuli. Using this optimal CRE promoter and the enhanced green fluorescent protein as the reporter, we have established a CRE reporter cell line. This cell line can be used to study the signal pathway by fluorescent microscope, fluorescence-activated cell analysis and luciferase assay. This cell line's sensitivity to forskolin, using the technique of fluorescence-activated cell sorting, was increased to approximately seven times that of its parental HEK 293 cell line, which is currently the most commonly used cell line in the field for the signal pathway study. Therefore, this newly created cell line is potentially useful for studying the signal pathway's modulators, which generally have weaker effect than its mediators. Our research has also established a general procedure for optimizing transcription-based reporter cell lines, which might be useful in performing the same task when studying many other transcription-based signal pathways. (c) 2010 Elsevier B.V. All rights reserved.
Mapping methyl jasmonate-mediated transcriptional reprogramming of metabolism and cell cycle progression in cultured Arabidopsis cells

PubMed Central

Pauwels, Laurens; Morreel, Kris; De Witte, Emilie; Lammertyn, Freya; Van Montagu, Marc; Boerjan, Wout; Inzé, Dirk; Goossens, Alain

2008-01-01

Jasmonates (JAs) are plant-specific signaling molecules that steer a diverse set of physiological and developmental processes. Pathogen attack and wounding inflicted by herbivores induce the biosynthesis of these hormones, triggering defense responses both locally and systemically. We report on alterations in the transcriptome of a fast-dividing cell culture of the model plant Arabidopsis thaliana after exogenous application of methyl JA (MeJA). Early MeJA response genes encoded the JA biosynthesis pathway proteins and key regulators of MeJA responses, including most JA ZIM domain proteins and MYC2, together with transcriptional regulators with potential, but yet unknown, functions in MeJA signaling. In a second transcriptional wave, MeJA reprogrammed cellular metabolism and cell cycle progression. Up-regulation of the monolignol biosynthesis gene set resulted in an increased production of monolignols and oligolignols, the building blocks of lignin. Simultaneously, MeJA repressed activation of M-phase genes, arresting the cell cycle in G2. MeJA-responsive transcription factors were screened for their involvement in early signaling events, in particular the regulation of JA biosynthesis. Parallel screens based on yeast one-hybrid and transient transactivation assays identified both positive (MYC2 and the AP2/ERF factor ORA47) and negative (the C2H2 Zn finger proteins STZ/ZAT10 and AZF2) regulators, revealing a complex control of the JA autoregulatory loop and possibly other MeJA-mediated downstream processes. PMID:18216250

Gene Regulation and Signal Transduction in the ICE-CBF-COR Signaling Pathway during Cold Stress in Plants.

PubMed

Wang, Da-Zhi; Jin, Ya-Nan; Ding, Xi-Han; Wang, Wen-Jia; Zhai, Shan-Shan; Bai, Li-Ping; Guo, Zhi-Fu

2017-10-01

Low temperature is an abiotic stress that adversely affects the growth and production of plants. Resistance and adaptation of plants to cold stress is dependent upon the activation of molecular networks and pathways involved in signal transduction and the regulation of cold-stress related genes. Because it has numerous and complex genes, regulation factors, and pathways, research on the ICE-CBF-COR signaling pathway is the most studied and detailed, which is thought to be rather important for cold resistance of plants. In this review, we focus on the function of each member, interrelation among members, and the influence of manipulators and repressors in the ICE-CBF-COR pathway. In addition, regulation and signal transduction concerning plant hormones, circadian clock, and light are discussed. The studies presented provide a detailed picture of the ICE-CBF-COR pathway.
Targeting the Notch signaling pathway in autoimmune diseases.

PubMed

Ma, Daoxin; Zhu, Yuanchao; Ji, Chunyan; Hou, Ming

2010-05-01

The Notch signaling pathway regulates a variety of processes and has been linked to diverse effects. Aberrant Notch function is important in several disorders. Pre-clinical studies have suggested that inhibition of Notch is an attractive approach to treat hematologic and solid malignancies. Many patients with refractory autoimmune diseases respond poorly to therapy and have significant morbidity and the treatment is highly toxic, so more effective therapies for autoimmune diseases are being examined. The role of the Notch pathway and therapeutic strategies targeting it in many illnesses, especially autoimmune diseases. The Notch pathway has unique and attractive advantages for targeting. Targeting it has already been trialed in many experiments, which may show better efficacy and fewer side effects compared with classical drugs for the treatment. Targeting Notch might provide etiological rather than symptomatic treatment. Various methods targeting the Notch pathway have been under investigation. Rational targeting of the Notch signaling pathway in cancer and some autoimmune diseases has proven to be successful. Classical drugs for the treatment of autoimmune diseases are inefficient and toxic to some extent, and targeting the Notch pathway is a promising therapeutic concept. However, there are still many questions about targeting Notch in autoimmune diseases, and further investigation will be needed.
The Hippo signaling pathway in liver regeneration and tumorigenesis.

PubMed

Hong, Lixin; Cai, Yabo; Jiang, Mingting; Zhou, Dawang; Chen, Lanfen

2015-01-01

The Hippo signaling pathway is an evolutionarily conserved signaling module that plays critical roles in liver size control and tumorigenesis. The Hippo pathway consists of a core kinase cascade in which the mammalian Ste20-like kinases (Mst1/2, orthologs of Drosophila Hippo) and their cofactor Salvador (Sav1) form a complex to phosphorylate and activate the large tumor suppressor (Lats1/2). Lats1/2 kinases in turn phosphorylate and inhibit the transcription co-activators, the Yes-associated protein (YAP) and the transcriptional co-activator with PDZ-binding motif (TAZ), two major downstream effectors of the Hippo pathway. Losses of the Hippo pathway components induce aberrant hepatomegaly and tumorigenesis, in which YAP coordinates regulation of cell proliferation and apoptosis and plays an essential role. This review summarizes the current findings of the regulation of Hippo signaling in liver regeneration and tumorigenesis, focusing on how the loss of tumor suppressor components of the Hippo pathway results in liver cancers and discussing the molecular mechanisms that regulate the expression and activation of its downstream effector YAP in liver tumorigenesis. © The Author 2014. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.
Basic Helix-Loop-Helix Transcription Factors JASMONATE-ASSOCIATED MYC2-LIKE1 (JAM1), JAM2, and JAM3 Are Negative Regulators of Jasmonate Responses in Arabidopsis1[W][OPEN

PubMed Central

Sasaki-Sekimoto, Yuko; Jikumaru, Yusuke; Obayashi, Takeshi; Saito, Hikaru; Masuda, Shinji; Kamiya, Yuji; Ohta, Hiroyuki; Shirasu, Ken

2013-01-01

Jasmonates regulate transcriptional reprogramming during growth, development, and defense responses. Jasmonoyl-isoleucine, an amino acid conjugate of jasmonic acid (JA), is perceived by the protein complex composed of the F-box protein CORONATINE INSENSITIVE1 (COI1) and JASMONATE ZIM DOMAIN (JAZ) proteins, leading to the ubiquitin-dependent degradation of JAZ proteins. This activates basic helix-loop-helix-type MYC transcription factors to regulate JA-responsive genes. Here, we show that the expression of genes encoding other basic helix-loop-helix transcription factors, JASMONATE ASSOCIATED MYC2-LIKE1 (JAM1), JAM2, and JAM3, is positively regulated in a COI1- and MYC2-dependent manner in Arabidopsis (Arabidopsis thaliana). However, contrary to myc2, the jam1jam2jam3 triple mutant exhibited shorter roots when treated with methyl jasmonate (MJ), indicating enhanced responsiveness to JA. Our genome-wide expression analyses revealed that key jasmonate metabolic genes as well as a set of genes encoding transcription factors that regulate the JA-responsive metabolic genes are negatively regulated by JAMs after MJ treatment. Consistently, loss of JAM genes resulted in higher accumulation of anthocyanin in MJ-treated plants as well as higher accumulation of JA and 12-hydroxyjasmonic acid in wounded plants. These results show that JAMs negatively regulate the JA responses in a manner that is mostly antagonistic to MYC2. PMID:23852442
Inhibition of the adrenomedullin/nitric oxide signaling pathway in early diabetic retinopathy.

PubMed

Blom, Jan J; Giove, Thomas J; Favazza, Tara L; Akula, James D; Eldred, William D

2011-06-01

The nitric oxide (NO) signaling pathway is integrally involved in visual processing and changes in the NO pathway are measurable in eyes of diabetic patients. The small peptide adrenomedullin (ADM) can activate a signaling pathway to increase the enzyme activity of neuronal nitric oxide synthase (nNOS). ADM levels are elevated in eyes of diabetic patients and therefore, ADM may play a role in the pathology of diabetic retinopathy. The goal of this research was to test the effects of inhibiting the ADM/NO signaling pathway in early diabetic retinopathy. Inhibition of this pathway decreased NO production in high-glucose retinal cultures. Treating diabetic mice with the PKC β inhibitor ruboxistaurin for 5 weeks lowered ADM mRNA levels and ADM-like immunoreactivity and preserved retinal function as assessed by electroretinography. The results of this study indicate that inhibiting the ADM/NO signaling pathway prevents neuronal pathology and functional losses in early diabetic retinopathy.
Elucidation of defense-related signaling responses to spot blotch infection in bread wheat (Triticum aestivum L.).

PubMed

Sahu, Ranabir; Sharaff, Murali; Pradhan, Maitree; Sethi, Avinash; Bandyopadhyay, Tirthankar; Mishra, Vinod K; Chand, Ramesh; Chowdhury, Apurba K; Joshi, Arun K; Pandey, Shree P

2016-04-01

Spot blotch disease, caused by Bipolaris sorokiniana, is an important threat to wheat, causing an annual loss of ~17%. Under epidemic conditions, these losses may be 100%, yet the molecular responses of wheat to spot blotch remain almost uncharacterized. Moreover, defense-related phytohormone signaling genes have been poorly characterized in wheat. Here, we have identified 18 central components of salicylic acid (SA), jasmonic acid (JA), ethylene (ET), and enhanced disease susceptibility 1 (EDS1) signaling pathways as well as the genes of the phenylpropanoid pathway in wheat. In time-course experiments, we characterized the reprogramming of expression of these pathways in two contrasting genotypes: Yangmai #6 (resistant to spot blotch) and Sonalika (susceptible to spot blotch). We further evaluated the performance of a population of recombinant inbred lines (RILs) by crossing Yangmai#6 and Sonalika (parents) and subsequent selfing to F10 under field conditions in trials at multiple locations. We characterized the reprogramming of defense-related signaling in these RILs as a consequence of spot blotch attack. During resistance to spot blotch attack, wheat strongly elicits SA signaling (SA biogenesis as well as the NPR1-dependent signaling pathway), along with WRKY33 transcription factor, followed by an enhanced expression of phenylpropanoid pathway genes. These may lead to accumulation of phenolics-based defense metabolites that may render resistance against spot blotch. JA signaling may synergistically contribute to the resistance. Failure to elicit SA (and possibly JA) signaling may lead to susceptibility against spot blotch infection in wheat. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.
The Jasmonate-Activated Transcription Factor MdMYC2 Regulates ETHYLENE RESPONSE FACTOR and Ethylene Biosynthetic Genes to Promote Ethylene Biosynthesis during Apple Fruit Ripening[OPEN

PubMed Central

Xu, Yaxiu; Zhang, Lichao; Ji, Yinglin; Tan, Dongmei; Yuan, Hui

2017-01-01

The plant hormone ethylene is critical for ripening in climacteric fruits, including apple (Malus domestica). Jasmonate (JA) promotes ethylene biosynthesis in apple fruit, but the underlying molecular mechanism is unclear. Here, we found that JA-induced ethylene production in apple fruit is dependent on the expression of MdACS1, an ACC synthase gene involved in ethylene biosynthesis. The expression of MdMYC2, encoding a transcription factor involved in the JA signaling pathway, was enhanced by MeJA treatment in apple fruits, and MdMYC2 directly bound to the promoters of both MdACS1 and the ACC oxidase gene MdACO1 and enhanced their transcription. Furthermore, MdMYC2 bound to the promoter of MdERF3, encoding a transcription factor involved in the ethylene-signaling pathway, thereby activating MdACS1 transcription. We also found that MdMYC2 interacted with MdERF2, a suppressor of MdERF3 and MdACS1. This protein interaction prevented MdERF2 from interacting with MdERF3 and from binding to the MdACS1 promoter, leading to increased transcription of MdACS1. Collectively, these results indicate that JA promotes ethylene biosynthesis through the regulation of MdERFs and ethylene biosynthetic genes by MdMYC2. PMID:28550149
Salicylic acid and jasmonic acid are essential for systemic resistance against tobacco mosaic virus in Nicotiana benthamiana.

PubMed

Zhu, Feng; Xi, De-Hui; Yuan, Shu; Xu, Fei; Zhang, Da-Wei; Lin, Hong-Hui

2014-06-01

Systemic resistance is induced by pathogens and confers protection against a broad range of pathogens. Recent studies have indicated that salicylic acid (SA) derivative methyl salicylate (MeSA) serves as a long-distance phloem-mobile systemic resistance signal in tobacco, Arabidopsis, and potato. However, other experiments indicate that jasmonic acid (JA) is a critical mobile signal. Here, we present evidence suggesting both MeSA and methyl jasmonate (MeJA) are essential for systemic resistance against Tobacco mosaic virus (TMV), possibly acting as the initiating signals for systemic resistance. Foliar application of JA followed by SA triggered the strongest systemic resistance against TMV. Furthermore, we use a virus-induced gene-silencing-based genetics approach to investigate the function of JA and SA biosynthesis or signaling genes in systemic response against TMV infection. Silencing of SA or JA biosynthetic and signaling genes in Nicotiana benthamiana plants increased susceptibility to TMV. Genetic experiments also proved the irreplaceable roles of MeSA and MeJA in systemic resistance response. Systemic resistance was compromised when SA methyl transferase or JA carboxyl methyltransferase, which are required for MeSA and MeJA formation, respectively, were silenced. Moreover, high-performance liquid chromatography-mass spectrometry analysis indicated that JA and MeJA accumulated in phloem exudates of leaves at early stages and SA and MeSA accumulated at later stages, after TMV infection. Our data also indicated that JA and MeJA could regulate MeSA and SA production. Taken together, our results demonstrate that (Me)JA and (Me)SA are required for systemic resistance response against TMV.
Induced Plant Defense Responses against Chewing Insects. Ethylene Signaling Reduces Resistance of Arabidopsis against Egyptian Cotton Worm But Not Diamondback Moth1

PubMed Central

Stotz, Henrik U.; Pittendrigh, Barry R.; Kroymann, Jürgen; Weniger, Kerstin; Fritsche, Jacqueline; Bauke, Antje; Mitchell-Olds, Thomas

2000-01-01

The induction of plant defenses by insect feeding is regulated via multiple signaling cascades. One of them, ethylene signaling, increases susceptibility of Arabidopsis to the generalist herbivore Egyptian cotton worm (Spodoptera littoralis; Lepidoptera: Noctuidae). The hookless1 mutation, which affects a downstream component of ethylene signaling, conferred resistance to Egyptian cotton worm as compared with wild-type plants. Likewise, ein2, a mutant in a central component of the ethylene signaling pathway, caused enhanced resistance to Egyptian cotton worm that was similar in magnitude to hookless1. Moreover, pretreatment of plants with ethephon (2-chloroethanephosphonic acid), a chemical that releases ethylene, elevated plant susceptibility to Egyptian cotton worm. By contrast, these mutations in the ethylene-signaling pathway had no detectable effects on diamondback moth (Plutella xylostella) feeding. It is surprising that this is not due to nonactivation of defense signaling, because diamondback moth does induce genes that relate to wound-response pathways. Of these wound-related genes, jasmonic acid regulates a novel β-glucosidase 1 (BGL1), whereas ethylene controls a putative calcium-binding elongation factor hand protein. These results suggest that a specialist insect herbivore triggers general wound-response pathways in Arabidopsis but, unlike a generalist herbivore, does not react to ethylene-mediated physiological changes. PMID:11080278
YAP regulates neuronal differentiation through Sonic hedgehog signaling pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Yi-Ting; Ding, Jing-Ya; Li, Ming-Yang

2012-09-10

Tight regulation of cell numbers by controlling cell proliferation and apoptosis is important during development. Recently, the Hippo pathway has been shown to regulate tissue growth and organ size in Drosophila. In mammalian cells, it also affects cell proliferation and differentiation in various tissues, including the nervous system. Interplay of several signaling cascades, such as Notch, Wnt, and Sonic Hedgehog (Shh) pathways, control cell proliferation during neuronal differentiation. However, it remains unclear whether the Hippo pathway coordinates with other signaling cascades in regulating neuronal differentiation. Here, we used P19 cells, a mouse embryonic carcinoma cell line, as a model tomore » study roles of YAP, a core component of the Hippo pathway, in neuronal differentiation. P19 cells can be induced to differentiate into neurons by expressing a neural bHLH transcription factor gene Ascl1. Our results showed that YAP promoted cell proliferation and inhibited neuronal differentiation. Expression of Yap activated Shh but not Wnt or Notch signaling activity during neuronal differentiation. Furthermore, expression of Yap increased the expression of Patched homolog 1 (Ptch1), a downstream target of the Shh signaling. Knockdown of Gli2, a transcription factor of the Shh pathway, promoted neuronal differentiation even when Yap was over-expressed. We further demonstrated that over-expression of Yap inhibited neuronal differentiation in primary mouse cortical progenitors and Gli2 knockdown rescued the differentiation defect in Yap over-expressing cells. In conclusion, our study reveals that Shh signaling acts downstream of YAP in regulating neuronal differentiation. -- Highlights: Black-Right-Pointing-Pointer YAP promotes cell proliferation and inhibits neuronal differentiation in P19 cells. Black-Right-Pointing-Pointer YAP promotes Sonic hedgehog signaling activity during neuronal differentiation. Black-Right-Pointing-Pointer Knockdown of Gli2 rescues the
Airborne signals from Trichoderma fungi stimulate iron uptake responses in roots resulting in priming of jasmonic acid-dependent defences in shoots of Arabidopsis thaliana and Solanum lycopersicum.

PubMed

Martínez-Medina, Ainhoa; Van Wees, Saskia C M; Pieterse, Corné M J

2017-11-01

Root colonization by Trichoderma fungi can trigger induced systemic resistance (ISR). In Arabidopsis, Trichoderma-ISR relies on the transcription factor MYB72, which plays a dual role in the onset of ISR and the activation of Fe uptake responses. Volatile compounds (VCs) from rhizobacteria are important elicitors of MYB72 in Arabidopsis roots. Here, we investigated the mode of action of VCs from Trichoderma fungi in the onset of ISR and Fe uptake responses. VCs from Trichoderma asperellum and Trichoderma harzianum were applied in an in vitro split-plate system with Arabidopsis or tomato seedlings. Locally, Trichoderma-VCs triggered MYB72 expression and molecular, physiological and morphological Fe uptake mechanisms in Arabidopsis roots. In leaves, Trichoderma-VCs primed jasmonic acid-dependent defences, leading to an enhanced resistance against Botrytis cinerea. By using Arabidopsis micrografts of VCs-exposed rootstocks and non-exposed scions, we demonstrated that perception of Trichoderma-VCs by the roots leads to a systemic signal that primes shoots for enhanced defences. Trichoderma-VCs also elicited Fe deficiency responses and shoot immunity in tomato, suggesting that this phenomenon is expressed in different plant species. Our results indicate that Trichoderma-VCs trigger locally a readjustment of Fe homeostasis in roots, which links to systemic elicitation of ISR by priming of jasmonic acid-dependent defences. © 2017 John Wiley & Sons Ltd.
Transplantation of prokaryotic two-component signaling pathways into mammalian cells.

PubMed

Hansen, Jonathan; Mailand, Erik; Swaminathan, Krishna Kumar; Schreiber, Joerg; Angelici, Bartolomeo; Benenson, Yaakov

2014-11-04

Signaling pathway engineering is a promising route toward synthetic biological circuits. Histidine-aspartate phosphorelays are thought to have evolved in prokaryotes where they form the basis for two-component signaling. Tyrosine-serine-threonine phosphorelays, exemplified by MAP kinase cascades, are predominant in eukaryotes. Recently, a prokaryotic two-component pathway was implemented in a plant species to sense environmental trinitrotoluene. We reasoned that "transplantation" of two-component pathways into mammalian host could provide an orthogonal and diverse toolkit for a variety of signal processing tasks. Here we report that two-component pathways could be partially reconstituted in mammalian cell culture and used for programmable control of gene expression. To enable this reconstitution, coding sequences of histidine kinase (HK) and response regulator (RR) components were codon-optimized for human cells, whereas the RRs were fused with a transactivation domain. Responsive promoters were furnished by fusing DNA binding sites in front of a minimal promoter. We found that coexpression of HKs and their cognate RRs in cultured mammalian cells is necessary and sufficient to strongly induce gene expression even in the absence of pathways' chemical triggers in the medium. Both loss-of-function and constitutive mutants behaved as expected. We further used the two-component signaling pathways to implement two-input logical AND, NOR, and OR gene regulation. Thus, two-component systems can be applied in different capacities in mammalian cells and their components can be used for large-scale synthetic gene circuits.
Discovering relationships between nuclear receptor signaling pathways, genes, and tissues in Transcriptomine.

PubMed

Becnel, Lauren B; Ochsner, Scott A; Darlington, Yolanda F; McOwiti, Apollo; Kankanamge, Wasula H; Dehart, Michael; Naumov, Alexey; McKenna, Neil J

2017-04-25

We previously developed a web tool, Transcriptomine, to explore expression profiling data sets involving small-molecule or genetic manipulations of nuclear receptor signaling pathways. We describe advances in biocuration, query interface design, and data visualization that enhance the discovery of uncharacterized biology in these pathways using this tool. Transcriptomine currently contains about 45 million data points encompassing more than 2000 experiments in a reference library of nearly 550 data sets retrieved from public archives and systematically curated. To make the underlying data points more accessible to bench biologists, we classified experimental small molecules and gene manipulations into signaling pathways and experimental tissues and cell lines into physiological systems and organs. Incorporation of these mappings into Transcriptomine enables the user to readily evaluate tissue-specific regulation of gene expression by nuclear receptor signaling pathways. Data points from animal and cell model experiments and from clinical data sets elucidate the roles of nuclear receptor pathways in gene expression events accompanying various normal and pathological cellular processes. In addition, data sets targeting non-nuclear receptor signaling pathways highlight transcriptional cross-talk between nuclear receptors and other signaling pathways. We demonstrate with specific examples how data points that exist in isolation in individual data sets validate each other when connected and made accessible to the user in a single interface. In summary, Transcriptomine allows bench biologists to routinely develop research hypotheses, validate experimental data, or model relationships between signaling pathways, genes, and tissues. Copyright © 2017, American Association for the Advancement of Science.
Identification of jasmonic acid and its methyl ester as gum-inducing factors in tulips.

PubMed

Skrzypek, Edyta; Miyamoto, Kensuke; Saniewski, Marian; Ueda, Junichi

2005-02-01

The purpose of this study was to identify endogenous factors that induce gummosis and to show their role in gummosis in tulip (Tulipa gesneriana L. cv. Apeldoorn) stems. Using procedures to detect endogenous factors that induce gum in the stem of tulips, jasmonic acid (JA) and methyl jasmonate (JA-Me) were successfully identified using gas-liquid chromatography-mass spectrometry. Total amounts of JA and JA-Me designated as jasmonates in tulip stems were also estimated at about 70-80 ng/g fresh weight, using deuterium-labeled jasmonates as internal standards. The application of JA and JA-Me as lanolin pastes substantially induced gums in tulip stems with ethylene production. The application of ethephon, an ethylene-generating compound, however, induced no gummosis although it slightly affected jasmonate content in tulip stems. These results strongly suggest that JA and JA-Me are endogenous factors that induce gummosis in tulip stems.
The Epiphytic Fungus Pseudozyma aphidis Induces Jasmonic Acid- and Salicylic Acid/Nonexpressor of PR1-Independent Local and Systemic Resistance1[C][W

PubMed Central

Buxdorf, Kobi; Rahat, Ido; Gafni, Aviva; Levy, Maggie

2013-01-01

Pseudozyma spp. are yeast-like fungi, classified in the Ustilaginales, which are mostly epiphytic or saprophytic and are not pathogenic to plants. Several Pseudozyma species have been reported to exhibit biological activity against powdery mildews. However, previous studies have reported that Pseudozyma aphidis, which can colonize plant surfaces, is not associated with the ‎‎collapse of powdery ‎mildew colonies. In this report, we describe a novel P. aphidis strain and study its interactions with its plant host and the plant pathogen Botrytis cinerea. This isolate was found to secrete extracellular metabolites that inhibit various fungal pathogens in vitro and significantly reduce B. cinerea infection in vivo. Moreover, P. aphidis sensitized Arabidopsis (Arabidopsis thaliana) plants’ defense machinery via local and systemic induction of PATHOGENESIS-RELATED1 (PR1) and PLANT DEFENSIN1.2 (PDF1.2) expression. P. aphidis also reduced B. cinerea infection, locally and systemically, in Arabidopsis mutants impaired in jasmonic acid (JA) or salicylic acid (SA) signaling. Thus, in addition to direct inhibition, P. aphidis may inhibit B. cinerea infection via induced resistance in a manner independent of SA, JA, and Nonexpressor of PR1 (NPR1). P. aphidis primed the plant defense machinery and induced stronger activation of PDF1.2 after B. cinerea infection. Finally, P. aphidis fully or partially reconstituted PR1 and PDF1.2 expression in npr1-1 mutant and in plants with the SA hydroxylase NahG transgene, but not in a jasmonate resistant1-1 mutant, after B. cinerea infection, suggesting that P. aphidis can bypass the SA/NPR1, but not JA, pathway to activate PR genes. Thus, either partial gene activation is sufficient to induce resistance, or the resistance is not directed solely through PR1 and PDF1.2 but probably through other pathogen-resistance genes or pathways as well. PMID:23388119
Kinetic insulation as an effective mechanism for achieving pathway specificity in intracellular signaling networks

PubMed Central

Behar, Marcelo; Dohlman, Henrik G.; Elston, Timothy C.

2007-01-01

Intracellular signaling pathways that share common components often elicit distinct physiological responses. In most cases, the biochemical mechanisms responsible for this signal specificity remain poorly understood. Protein scaffolds and cross-inhibition have been proposed as strategies to prevent unwanted cross-talk. Here, we report a mechanism for signal specificity termed “kinetic insulation.” In this approach signals are selectively transmitted through the appropriate pathway based on their temporal profile. In particular, we demonstrate how pathway architectures downstream of a common component can be designed to efficiently separate transient signals from signals that increase slowly over time. Furthermore, we demonstrate that upstream signaling proteins can generate the appropriate input to the common pathway component regardless of the temporal profile of the external stimulus. Our results suggest that multilevel signaling cascades may have evolved to modulate the temporal profile of pathway activity so that stimulus information can be efficiently encoded and transmitted while ensuring signal specificity. PMID:17913886
Role of Tomato Lipoxygenase D in Wound-Induced Jasmonate Biosynthesis and Plant Immunity to Insect Herbivores

PubMed Central

Li, Shuyu; Wang, Bao; Huang, Tingting; Du, Minmin; Sun, Jiaqiang; Kang, Le; Li, Chang-Bao; Li, Chuanyou

2013-01-01

In response to insect attack and mechanical wounding, plants activate the expression of genes involved in various defense-related processes. A fascinating feature of these inducible defenses is their occurrence both locally at the wounding site and systemically in undamaged leaves throughout the plant. Wound-inducible proteinase inhibitors (PIs) in tomato (Solanum lycopersicum) provide an attractive model to understand the signal transduction events leading from localized injury to the systemic expression of defense-related genes. Among the identified intercellular molecules in regulating systemic wound response of tomato are the peptide signal systemin and the oxylipin signal jasmonic acid (JA). The systemin/JA signaling pathway provides a unique opportunity to investigate, in a single experimental system, the mechanism by which peptide and oxylipin signals interact to coordinate plant systemic immunity. Here we describe the characterization of the tomato suppressor of prosystemin-mediated responses8 (spr8) mutant, which was isolated as a suppressor of (pro)systemin-mediated signaling. spr8 plants exhibit a series of JA-dependent immune deficiencies, including the inability to express wound-responsive genes, abnormal development of glandular trichomes, and severely compromised resistance to cotton bollworm (Helicoverpa armigera) and Botrytis cinerea. Map-based cloning studies demonstrate that the spr8 mutant phenotype results from a point mutation in the catalytic domain of TomLoxD, a chloroplast-localized lipoxygenase involved in JA biosynthesis. We present evidence that overexpression of TomLoxD leads to elevated wound-induced JA biosynthesis, increased expression of wound-responsive genes and, therefore, enhanced resistance to insect herbivory attack and necrotrophic pathogen infection. These results indicate that TomLoxD is involved in wound-induced JA biosynthesis and highlight the application potential of this gene for crop protection against insects and
Role of tomato lipoxygenase D in wound-induced jasmonate biosynthesis and plant immunity to insect herbivores.

PubMed

Yan, Liuhua; Zhai, Qingzhe; Wei, Jianing; Li, Shuyu; Wang, Bao; Huang, Tingting; Du, Minmin; Sun, Jiaqiang; Kang, Le; Li, Chang-Bao; Li, Chuanyou

2013-01-01

In response to insect attack and mechanical wounding, plants activate the expression of genes involved in various defense-related processes. A fascinating feature of these inducible defenses is their occurrence both locally at the wounding site and systemically in undamaged leaves throughout the plant. Wound-inducible proteinase inhibitors (PIs) in tomato (Solanum lycopersicum) provide an attractive model to understand the signal transduction events leading from localized injury to the systemic expression of defense-related genes. Among the identified intercellular molecules in regulating systemic wound response of tomato are the peptide signal systemin and the oxylipin signal jasmonic acid (JA). The systemin/JA signaling pathway provides a unique opportunity to investigate, in a single experimental system, the mechanism by which peptide and oxylipin signals interact to coordinate plant systemic immunity. Here we describe the characterization of the tomato suppressor of prosystemin-mediated responses8 (spr8) mutant, which was isolated as a suppressor of (pro)systemin-mediated signaling. spr8 plants exhibit a series of JA-dependent immune deficiencies, including the inability to express wound-responsive genes, abnormal development of glandular trichomes, and severely compromised resistance to cotton bollworm (Helicoverpa armigera) and Botrytis cinerea. Map-based cloning studies demonstrate that the spr8 mutant phenotype results from a point mutation in the catalytic domain of TomLoxD, a chloroplast-localized lipoxygenase involved in JA biosynthesis. We present evidence that overexpression of TomLoxD leads to elevated wound-induced JA biosynthesis, increased expression of wound-responsive genes and, therefore, enhanced resistance to insect herbivory attack and necrotrophic pathogen infection. These results indicate that TomLoxD is involved in wound-induced JA biosynthesis and highlight the application potential of this gene for crop protection against insects and
Control of proliferation and cancer growth by the Hippo signaling pathway

PubMed Central

Ehmer, Ursula; Sage, Julien

2015-01-01

The control of cell division is essential for normal development and the maintenance of cellular homeostasis. Abnormal cell proliferation is associated with multiple pathological states, including cancer. While the Hippo/YAP signaling pathway was initially thought to control organ size and growth, increasing evidence indicates that this pathway also plays a major role in the control of proliferation independent of organ size control. In particular, accumulating evidence indicates that the Hippo/YAP signaling pathway functionally interacts with multiple other cellular pathways and serves as a central node in the regulation of cell division, especially in cancer cells. Here recent observations are highlighted that connect Hippo/YAP signaling to transcription, the basic cell cycle machinery, and the control of cell division. Furthermore, the oncogenic and tumor suppressive attributes of YAP/TAZ are reviewed which emphasizes the relevance of the Hippo pathway in cancer. PMID:26432795
Identification of a Novel Gnao-Mediated Alternate Olfactory Signaling Pathway in Murine OSNs.

PubMed

Scholz, Paul; Mohrhardt, Julia; Jansen, Fabian; Kalbe, Benjamin; Haering, Claudia; Klasen, Katharina; Hatt, Hanns; Osterloh, Sabrina

2016-01-01

It is generally agreed that in olfactory sensory neurons (OSNs), the binding of odorant molecules to their specific olfactory receptor (OR) triggers a cAMP-dependent signaling cascade, activating cyclic-nucleotide gated (CNG) channels. However, considerable controversy dating back more than 20 years has surrounded the question of whether alternate signaling plays a role in mammalian olfactory transduction. In this study, we demonstrate a specific alternate signaling pathway in Olfr73-expressing OSNs. Methylisoeugenol (MIEG) and at least one other known weak Olfr73 agonist (Raspberry Ketone) trigger a signaling cascade independent from the canonical pathway, leading to the depolarization of the cell. Interestingly, this pathway is mediated by Gnao activation, leading to Cl(-) efflux; however, the activation of adenylyl cyclase III (ACIII), the recruitment of Ca(2+) from extra-or intracellular stores, and phosphatidylinositol 3-kinase-dependent signaling (PI signaling) are not involved. Furthermore, we demonstrated that our newly identified pathway coexists with the canonical olfactory cAMP pathway in the same OSN and can be triggered by the same OR in a ligand-selective manner. We suggest that this pathway might reflect a mechanism for odor recognition predominantly used in early developmental stages before olfactory cAMP signaling is fully developed. Taken together, our findings support the existence of at least one odor-induced alternate signal transduction pathway in native OSNs mediated by Olfr73 in a ligand-selective manner.

Wnt signalling pathway parameters for mammalian cells.

PubMed

Tan, Chin Wee; Gardiner, Bruce S; Hirokawa, Yumiko; Layton, Meredith J; Smith, David W; Burgess, Antony W

2012-01-01

Wnt/β-catenin signalling regulates cell fate, survival, proliferation and differentiation at many stages of mammalian development and pathology. Mutations of two key proteins in the pathway, APC and β-catenin, have been implicated in a range of cancers, including colorectal cancer. Activation of Wnt signalling has been associated with the stabilization and nuclear accumulation of β-catenin and consequential up-regulation of β-catenin/TCF gene transcription. In 2003, Lee et al. constructed a computational model of Wnt signalling supported by experimental data from analysis of time-dependent concentration of Wnt signalling proteins in Xenopus egg extracts. Subsequent studies have used the Xenopus quantitative data to infer Wnt pathway dynamics in other systems. As a basis for understanding Wnt signalling in mammalian cells, a confocal live cell imaging measurement technique is developed to measure the cell and nuclear volumes of MDCK, HEK293T cells and 3 human colorectal cancer cell lines and the concentrations of Wnt signalling proteins β-catenin, Axin, APC, GSK3β and E-cadherin. These parameters provide the basis for formulating Wnt signalling models for kidney/intestinal epithelial mammalian cells. There are significant differences in concentrations of key proteins between Xenopus extracts and mammalian whole cell lysates. Higher concentrations of Axin and lower concentrations of APC are present in mammalian cells. Axin concentrations are greater than APC in kidney epithelial cells, whereas in intestinal epithelial cells the APC concentration is higher than Axin. Computational simulations based on Lee's model, with this new data, suggest a need for a recalibration of the model.A quantitative understanding of Wnt signalling in mammalian cells, in particular human colorectal cancers requires a detailed understanding of the concentrations of key protein complexes over time. Simulations of Wnt signalling in mammalian cells can be initiated with the parameters
PI3K/Akt signalling pathway and cancer.

PubMed

Fresno Vara, Juan Angel; Casado, Enrique; de Castro, Javier; Cejas, Paloma; Belda-Iniesta, Cristóbal; González-Barón, Manuel

2004-04-01

Phosphatidylinositol-3 kinases, PI3Ks, constitute a lipid kinase family characterized by their ability to phosphorylate inositol ring 3'-OH group in inositol phospholipids to generate the second messenger phosphatidylinositol-3,4,5-trisphosphate (PI-3,4,5-P(3)). RPTK activation results in PI(3,4,5)P(3) and PI(3,4)P(2) production by PI3K at the inner side of the plasma membrane. Akt interacts with these phospholipids, causing its translocation to the inner membrane, where it is phosphorylated and activated by PDK1 and PDK2. Activated Akt modulates the function of numerous substrates involved in the regulation of cell survival, cell cycle progression and cellular growth. In recent years, it has been shown that PI3K/Akt signalling pathway components are frequently altered in human cancers. Cancer treatment by chemotherapy and gamma-irradiation kills target cells primarily by the induction of apoptosis. However, the development of resistance to therapy is an important clinical problem. Failure to activate the apoptotic programme represents an important mode of drug resistance in tumor cells. Survival signals induced by several receptors are mediated mainly by PI3K/Akt, hence this pathway may decisively contribute to the resistant phenotype. Many of the signalling pathways involved in cellular transformation have been elucidated and efforts are underway to develop treatment strategies that target these specific signalling molecules or their downstream effectors. The PI3K/Akt pathway is involved in many of the mechanisms targeted by these new drugs, thus a better understanding of this crossroad can help to fully exploit the potential benefits of these new agents.
Tight Junction–Associated Signaling Pathways Modulate Cell Proliferation in Uveal Melanoma

PubMed Central

Jayagopal, Ashwath; Yang, Jin-Long; Haselton, Frederick R.; Chang, Min S.

2011-01-01

Purpose. To investigate the role of tight junction (TJ)–associated signaling pathways in the proliferation of uveal melanoma. Methods. Human uveal melanoma cell lines overexpressing the TJ molecule blood vessel epicardial substance (Bves) were generated. The effects of Bves overexpression on TJ protein expression, cell proliferation, and cell cycle distribution were quantified. In addition, localization and transcription activity of the TJ-associated protein ZO-1–associated nucleic acid binding protein (ZONAB) were evaluated using immunofluorescence and bioluminescence reporter assays to study the involvement of Bves signaling in cell proliferation-associated pathways. Results. Bves overexpression in uveal melanoma cell lines resulted in increased expression of the TJ proteins occludin and ZO-1, reduced cell proliferation, and increased sequestration of ZONAB at TJs and reduced ZONAB transcriptional activity. Conclusions. TJ proteins are present in uveal melanoma, and TJ-associated signaling pathways modulate cell signaling pathways relevant to proliferation in uveal melanoma. PMID:20861479
The emerging role of Hippo signaling pathway in regulating osteoclast formation.

PubMed

Yang, Wanlei; Han, Weiqi; Qin, An; Wang, Ziyi; Xu, Jiake; Qian, Yu

2018-06-01

A delicate balance between osteoblastic bone formation and osteoclastic bone resorption is crucial for bone homeostasis. This process is regulated by the Hippo signaling pathway including key regulatory molecules RASSF2, NF2, MST1/2, SAV1, LATS1/2, MOB1, YAP, and TAZ. It is well established that the Hippo signaling pathway plays an important part in regulating osteoblast differentiation, but its role in osteoclast formation and activation remains poorly understood. In this review, we discuss the emerging role of Hippo-signaling pathway in osteoclast formation and bone homeostasis. It is revealed that specific molecules of the Hippo-signaling pathway take part in a stage specific regulation in pre-osteoclast proliferation, osteoclast differentiation and osteoclast apoptosis and survival. Upon activation, MST and LAST, transcriptional co-activators YAP and TAZ bind to the members of the TEA domain (TEAD) family transcription factors, and influence osteoclast differentiation via regulating the expression of downstream target genes such as connective tissue growth factor (CTGF/CCN2) and cysteine-rich protein 61 (CYR61/CCN1). In addition, through interacting or cross talking with RANKL-mediated signaling cascades including NF-κB, MAPKs, AP1, and NFATc1, Hippo-signaling molecules such as YAP/TAZ/TEAD complex, RASSF2, MST2, and Ajuba could also potentially modulate osteoclast differentiation and function. Elucidating the roles of the Hippo-signaling pathway in osteoclast development and specific molecules involved is important for understanding the mechanism of bone homeostasis and diseases. © 2017 Wiley Periodicals, Inc.
Hippo-YAP signaling pathway: A new paradigm for cancer therapy.

PubMed

Ma, Yanlei; Yang, Yongzhi; Wang, Feng; Wei, Qing; Qin, Huanlong

2015-11-15

In the past decades, the Hippo signaling pathway has been delineated and shown to play multiple roles in the control of organ size in both Drosophila and mammals. In mammals, the Hippo pathway is a kinase cascade leading from Mst1/2 to YAP and its paralog TAZ. Several studies have demonstrated that YAP/TAZ is a candidate oncogene and that other members of the Hippo pathway are tumor suppressive genes. The dysregulation of the Hippo pathway has been observed in a variety of cancers. This review chronicles the recent progress in elucidating the function of Hippo signaling in tumorigenesis and provide a rich source of potential targets for cancer therapy. © 2014 UICC.
JAK/STAT signaling pathway-mediated immune response in silkworm (Bombyx mori) challenged by Beauveria bassiana.

PubMed

Geng, Tao; Lv, Ding-Ding; Huang, Yu-Xia; Hou, Cheng-Xiang; Qin, Guang-Xing; Guo, Xi-Jie

2016-12-20

Innate immunity was critical in insects defensive system and able to be induced by Janus kinase/signal transducer and activator of transcription cascade transduction (JAK/STAT) signaling pathway. Currently, it had been identified many JAK/STAT signaling pathway-related genes in silkworm, but little function was known on insect innate immunity. To explore the roles of JAK/STAT pathway in antifungal immune response in silkworm (Bombyx mori) against Beauveria bassiana infection, the expression patterns of B. mori C-type lectin 5 (BmCTL5) and genes encoding 6 components of JAK/STAT signaling pathway in silkworm challenged by B. bassiana were analyzed using quantitative real time PCR. Meanwhile the activation of JAK/STAT signaling pathway by various pathogenic micro-organisms and the affect of JAK/STAT signaling pathway inhibitors on antifungal activity in silkworm hemolymph was also detected. Moreover, RNAi assay of BmCTL5 and the affect on expression levels of signaling factors were also analyzed. We found that JAK/STAT pathway could be obviously activated in silkworm challenged with B. bassiana and had no response to bacteria and B. mori cytoplasmic polyhedrosis virus (BmCPV). However, the temporal expression patterns of JAK/STAT signaling pathway related genes were significantly different. B. mori downstream receptor kinase (BmDRK) might be a positive regulator of JAK/STAT signaling pathway in silkworm against B. bassiana infection. Moreover, antifungal activity assay showed that the suppression of JAK/STAT signaling pathway by inhibitors could significantly inhibit the antifungal activity in hemolymph and resulted in increased sensitivity of silkworm to B. bassiana infection, indicating that JAK/STAT signaling pathway might be involved in the synthesis and secretion of antifungal substances. The results of RNAi assays suggested that BmCTL5 might be one pattern recognition receptors for JAK/STAT signaling pathway in silkworm. These findings yield insights for better
A chloroplast lipoxygenase is required for wound-induced jasmonic acid accumulation in Arabidopsis.

PubMed Central

Bell, E; Creelman, R A; Mullet, J E

1995-01-01

Plant lipoxygenases are thought to be involved in the biosynthesis of lipid-derived signaling molecules. The potential involvement of a specific Arabidopsis thaliana lipoxygenase isozyme, LOX2, in the biosynthesis of the plant growth regulators jasmonic acid (JA) and abscisic acid was investigated. Our characterization of LOX2 indicates that the protein is targeted to chloroplasts. The physiological role of this chloroplast lipoxygenase was analyzed in transgenic plants where cosuppression reduced LOX2 accumulation. The reduction in LOX2 levels caused no obvious changes in plant growth or in the accumulation of abscisic acid. However, the wound-induced accumulation of JA observed in control plants was absent in leaves of transgenic plants that lacked LOX2. Thus, LOX2 is required for the wound-induced synthesis of the plant growth regulator JA in leaves. We also examined the expression of a wound- and JA-inducible Arabidopsis gene, vsp, in transgenic and control plants. Leaves of transgenic plants lacking LOX2 accumulated less vsp mRNA than did control leaves in response to wounding. This result suggests that wound-induced JA (or some other LOX2-requiring component of the wound response pathway) is involved in the wound-induced regulation of this gene. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:7567995
A chloroplast lipoxygenase is required for wound-induced jasmonic acid accumulation in Arabidopsis.

PubMed

Bell, E; Creelman, R A; Mullet, J E

1995-09-12

Plant lipoxygenases are thought to be involved in the biosynthesis of lipid-derived signaling molecules. The potential involvement of a specific Arabidopsis thaliana lipoxygenase isozyme, LOX2, in the biosynthesis of the plant growth regulators jasmonic acid (JA) and abscisic acid was investigated. Our characterization of LOX2 indicates that the protein is targeted to chloroplasts. The physiological role of this chloroplast lipoxygenase was analyzed in transgenic plants where cosuppression reduced LOX2 accumulation. The reduction in LOX2 levels caused no obvious changes in plant growth or in the accumulation of abscisic acid. However, the wound-induced accumulation of JA observed in control plants was absent in leaves of transgenic plants that lacked LOX2. Thus, LOX2 is required for the wound-induced synthesis of the plant growth regulator JA in leaves. We also examined the expression of a wound- and JA-inducible Arabidopsis gene, vsp, in transgenic and control plants. Leaves of transgenic plants lacking LOX2 accumulated less vsp mRNA than did control leaves in response to wounding. This result suggests that wound-induced JA (or some other LOX2-requiring component of the wound response pathway) is involved in the wound-induced regulation of this gene.
Stress signaling pathways for the pathogenicity of Cryptococcus.

PubMed

Bahn, Yong-Sun; Jung, Kwang-Woo

2013-12-01

Sensing, responding, and adapting to the surrounding environment are crucial for all living organisms to survive, proliferate, and differentiate in their biological niches. This ability is also essential for Cryptococcus neoformans and its sibling species Cryptococcus gattii, as these pathogens have saprobic and parasitic life cycles in natural and animal host environments. The ability of Cryptococcus to cause fatal meningoencephalitis is highly related to its capability to remodel and optimize its metabolic and physiological status according to external cues. These cues act through multiple stress signaling pathways through a panoply of signaling components, including receptors/sensors, small GTPases, secondary messengers, kinases, transcription factors, and other miscellaneous adaptors or regulators. In this minireview, we summarize and highlight the importance of several stress signaling pathways that influence the pathogenicity of Cryptococcus and discuss future challenges in these areas.
Stress Signaling Pathways for the Pathogenicity of Cryptococcus

PubMed Central

Jung, Kwang-Woo

2013-01-01

Sensing, responding, and adapting to the surrounding environment are crucial for all living organisms to survive, proliferate, and differentiate in their biological niches. This ability is also essential for Cryptococcus neoformans and its sibling species Cryptococcus gattii, as these pathogens have saprobic and parasitic life cycles in natural and animal host environments. The ability of Cryptococcus to cause fatal meningoencephalitis is highly related to its capability to remodel and optimize its metabolic and physiological status according to external cues. These cues act through multiple stress signaling pathways through a panoply of signaling components, including receptors/sensors, small GTPases, secondary messengers, kinases, transcription factors, and other miscellaneous adaptors or regulators. In this minireview, we summarize and highlight the importance of several stress signaling pathways that influence the pathogenicity of Cryptococcus and discuss future challenges in these areas. PMID:24078305
Methyl jasmonate affects phenolic metabolism and gene expression in blueberry (Vaccinium corymbosum).

PubMed

Cocetta, Giacomo; Rossoni, Mara; Gardana, Claudio; Mignani, Ilaria; Ferrante, Antonio; Spinardi, Anna

2015-02-01

Blueberry (Vaccinium corymbosum) is a fruit very much appreciated by consumers for its antioxidant potential and health-promoting traits. Its beneficial potential properties are mainly due to a high content of anthocyanins and their amount can change after elicitation with methyl jasmonate. The aim of this work is to evaluate the changes in expression of several genes, accumulation of phenolic compounds and alterations in antioxidant potential in two different blueberry cultivars ('Duke' and 'Blueray') in response to methyl jasmonate (0.1 mM). Results showed that 9 h after treatment, the expression of phenylalanine ammonium lyase, chalcone synthase and anthocyanidin synthase genes was stimulated more in the 'Blueray' variety. Among the phenols measured an increase was recorded also for epicatechin and anthocyanin concentrations. 'Duke' is a richer sourche of anthocyanins compared to 'Blueray', treatment with methyl jasmonate promoted in 'Blueray' an increase in pigments as well as in the antioxidant potential, especially in fully ripe berries, but treated 'Duke' berries had greater levels, which were not induced by methyl jasmonate treatment. In conclusion, methyl jasmonate was, in some cases, an effective elicitor of phenolic metabolism and gene expression in blueberry, though with different intensity between cultivars. © 2014 Scandinavian Plant Physiology Society.
Regulation of Tissue Growth by the Mammalian Hippo Signaling Pathway

PubMed Central

Watt, Kevin I.; Harvey, Kieran F.; Gregorevic, Paul

2017-01-01

The integrative control of diverse biological processes such as proliferation, differentiation, apoptosis and metabolism is essential to maintain cellular and tissue homeostasis. Disruption of these underlie the development of many disease states including cancer and diabetes, as well as many of the complications that arise as a consequence of aging. These biological outputs are governed by many cellular signaling networks that function independently, and in concert, to convert changes in hormonal, mechanical and metabolic stimuli into alterations in gene expression. First identified in Drosophila melanogaster as a powerful mediator of cell division and apoptosis, the Hippo signaling pathway is a highly conserved regulator of mammalian organ size and functional capacity in both healthy and diseased tissues. Recent studies have implicated the pathway as an effector of diverse physiological cues demonstrating an essential role for the Hippo pathway as an integrative component of cellular homeostasis. In this review, we will: (a) outline the critical signaling elements that constitute the mammalian Hippo pathway, and how they function to regulate Hippo pathway-dependent gene expression and tissue growth, (b) discuss evidence that shows this pathway functions as an effector of diverse physiological stimuli and (c) highlight key questions in this developing field. PMID:29225579
The immune signaling pathways of Manduca sexta

PubMed Central

Cao, Xiaolong; He, Yan; Hu, Yingxia; Wang, Yang; Chen, Yun-Ru; Bryant, Bart; Clem, Rollie J.; Schwartz, Lawrence M.; Blissard, Gary; Jiang, Haobo

2015-01-01

Signal transduction pathways and their coordination are critically important for proper functioning of animal immune systems. Our knowledge of the constituents of the intracellular signaling network in insects mainly comes from genetic analyses in Drosophila melanogaster. To facilitate future studies of similar systems in the tobacco hornworm and other lepidopteran insects, we have identified and examined the homologous genes in the genome of Manduca sexta. Based on 1:1 orthologous relationships in most cases, we hypothesize that the Toll, Imd, MAPK-JNK-p38 and JAK-STAT pathways are intact and operative in this species, as are most of the regulatory mechanisms. Similarly, cellular processes such as autophagy, apoptosis and RNA interference probably function in similar ways, because their mediators and modulators are mostly conserved in this lepidopteran species. We have annotated a total of 186 genes encoding 199 proteins, studied their domain structures and evolution, and examined their mRNA levels in tissues at different life stages. Such information provides a genomic perspective of the intricate signaling system in a non-drosophiline insect. PMID:25858029
Autonomous rexinoid death signaling is suppressed by converging signaling pathways in immature leukemia cells.

PubMed

Benoit, G R; Flexor, M; Besançon, F; Altucci, L; Rossin, A; Hillion, J; Balajthy, Z; Legres, L; Ségal-Bendirdjian, E; Gronemeyer, H; Lanotte, M

2001-07-01

On their own, retinoid X receptor (RXR)-selective ligands (rexinoids) are silent in retinoic acid receptor (RAR)-RXR heterodimers, and no selective rexinoid program has been described as yet in cellular systems. We report here on the rexinoid signaling capacity that triggers apoptosis of immature promyelocytic NB4 cells as a default pathway in the absence of survival factors. Rexinoid-induced apoptosis displays all features of bona fide programmed cell death and is inhibited by RXR, but not RAR antagonists. Several types of survival signals block rexinoid-induced apoptosis. RARalpha agonists switch the cellular response toward differentiation and induce the expression of antiapoptosis factors. Activation of the protein kinase A pathway in the presence of rexinoid agonists induces maturation and blocks immature cell apoptosis. Addition of nonretinoid serum factors also blocks cell death but does not induce cell differentiation. Rexinoid-induced apoptosis is linked to neither the presence nor stability of the promyelocytic leukemia-RARalpha fusion protein and operates also in non-acute promyelocytic leukemia cells. Together our results support a model according to which rexinoids activate in certain leukemia cells a default death pathway onto which several other signaling paradigms converge. This pathway is entirely distinct from that triggered by RAR agonists, which control cell maturation and postmaturation apoptosis.
Role of the ceramide-signaling pathways in ionizing radiation-induced apoptosis.

PubMed

Vit, Jean-Philippe; Rosselli, Filippo

2003-11-27

Ionizing radiations (IR) exposure leads to damage on several cellular targets. How signals from different targets are integrated to determine the cell fate remains a controversial issue. Understanding the pathway(s) responsible(s) for the cell killing effect of the IR exposure is of prime importance in light of using radiations as anticancer agent or as diagnostic tool. In this study, we have established that IR-induced cell damage initiates two independent signaling pathways that lead to a biphasic intracellular ceramide increase. A transitory increase of ceramide is observed within minutes after IR exposure as a consequence of DNA damage-independent acid sphingomyelinase activation. Several hours after irradiation, a second wave of ceramide accumulation is observed depending on the DNA damage-dependent activation of ceramide synthase, which requires a signaling pathway involving ATM. Importantly, we have demonstrated that the late ceramide accumulation is also dependent on the first one and is rate limiting for the apoptotic process induced by IR. In conclusion, our observations suggest that ceramide is a major determinant of the IR-induced apoptotic process at the cross-point of different signal transduction pathways.
Targeting the Hippo Signaling Pathway for Tissue Regeneration and Cancer Therapy.

PubMed

Juan, Wen Chun; Hong, Wanjin

2016-08-30

The Hippo signaling pathway is a highly-conserved developmental pathway that plays an essential role in organ size control, tumor suppression, tissue regeneration and stem cell self-renewal. The YES-associated protein (YAP) and the transcriptional co-activator with PDZ-binding motif (TAZ) are two important transcriptional co-activators that are negatively regulated by the Hippo signaling pathway. By binding to transcription factors, especially the TEA domain transcription factors (TEADs), YAP and TAZ induce the expression of growth-promoting genes, which can promote organ regeneration after injury. Therefore, controlled activation of YAP and TAZ can be useful for regenerative medicine. However, aberrant activation of YAP and TAZ due to deregulation of the Hippo pathway or overexpression of YAP/TAZ and TEADs can promote cancer development. Hence, pharmacological inhibition of YAP and TAZ may be a useful approach to treat tumors with high YAP and/or TAZ activity. In this review, we present the mechanisms regulating the Hippo pathway, the role of the Hippo pathway in tissue repair and cancer, as well as a detailed analysis of the different strategies to target the Hippo signaling pathway and the genes regulated by YAP and TAZ for regenerative medicine and cancer therapy.
Evolution and Design Governing Signal Precision and Amplification in a Bacterial Chemosensory Pathway

PubMed Central

Espinosa, Leon; Baronian, Grégory; Molle, Virginie; Mauriello, Emilia M. F.; Brochier-Armanet, Céline; Mignot, Tâm

2015-01-01

Understanding the principles underlying the plasticity of signal transduction networks is fundamental to decipher the functioning of living cells. In Myxococcus xanthus, a particular chemosensory system (Frz) coordinates the activity of two separate motility systems (the A- and S-motility systems), promoting multicellular development. This unusual structure asks how signal is transduced in a branched signal transduction pathway. Using combined evolution-guided and single cell approaches, we successfully uncoupled the regulations and showed that the A-motility regulation system branched-off an existing signaling system that initially only controlled S-motility. Pathway branching emerged in part following a gene duplication event and changes in the circuit structure increasing the signaling efficiency. In the evolved pathway, the Frz histidine kinase generates a steep biphasic response to increasing external stimulations, which is essential for signal partitioning to the motility systems. We further show that this behavior results from the action of two accessory response regulator proteins that act independently to filter and amplify signals from the upstream kinase. Thus, signal amplification loops may underlie the emergence of new connectivity in signal transduction pathways. PMID:26291327
Linear effects models of signaling pathways from combinatorial perturbation data

PubMed Central

Szczurek, Ewa; Beerenwinkel, Niko

2016-01-01

Motivation: Perturbations constitute the central means to study signaling pathways. Interrupting components of the pathway and analyzing observed effects of those interruptions can give insight into unknown connections within the signaling pathway itself, as well as the link from the pathway to the effects. Different pathway components may have different individual contributions to the measured perturbation effects, such as gene expression changes. Those effects will be observed in combination when the pathway components are perturbed. Extant approaches focus either on the reconstruction of pathway structure or on resolving how the pathway components control the downstream effects. Results: Here, we propose a linear effects model, which can be applied to solve both these problems from combinatorial perturbation data. We use simulated data to demonstrate the accuracy of learning the pathway structure as well as estimation of the individual contributions of pathway components to the perturbation effects. The practical utility of our approach is illustrated by an application to perturbations of the mitogen-activated protein kinase pathway in Saccharomyces cerevisiae. Availability and Implementation: lem is available as a R package at http://www.mimuw.edu.pl/∼szczurek/lem. Contact: szczurek@mimuw.edu.pl; niko.beerenwinkel@bsse.ethz.ch Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27307630
Linear effects models of signaling pathways from combinatorial perturbation data.

PubMed

Szczurek, Ewa; Beerenwinkel, Niko

2016-06-15

Perturbations constitute the central means to study signaling pathways. Interrupting components of the pathway and analyzing observed effects of those interruptions can give insight into unknown connections within the signaling pathway itself, as well as the link from the pathway to the effects. Different pathway components may have different individual contributions to the measured perturbation effects, such as gene expression changes. Those effects will be observed in combination when the pathway components are perturbed. Extant approaches focus either on the reconstruction of pathway structure or on resolving how the pathway components control the downstream effects. Here, we propose a linear effects model, which can be applied to solve both these problems from combinatorial perturbation data. We use simulated data to demonstrate the accuracy of learning the pathway structure as well as estimation of the individual contributions of pathway components to the perturbation effects. The practical utility of our approach is illustrated by an application to perturbations of the mitogen-activated protein kinase pathway in Saccharomyces cerevisiaeAvailability and Implementation: lem is available as a R package at http://www.mimuw.edu.pl/∼szczurek/lem szczurek@mimuw.edu.pl; niko.beerenwinkel@bsse.ethz.ch Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.
An algorithm for modularization of MAPK and calcium signaling pathways: comparative analysis among different species.

PubMed

Nayak, Losiana; De, Rajat K

2007-12-01

Signaling pathways are large complex biochemical networks. It is difficult to analyze the underlying mechanism of such networks as a whole. In the present article, we have proposed an algorithm for modularization of signal transduction pathways. Unlike studying a signaling pathway as a whole, this enables one to study the individual modules (less complex smaller units) easily and hence to study the entire pathway better. A comparative study of modules belonging to different species (for the same signaling pathway) has been made, which gives an overall idea about development of the signaling pathways over the taken set of species of calcium and MAPK signaling pathways. The superior performance, in terms of biological significance, of the proposed algorithm over an existing community finding algorithm of Newman [Newman MEJ. Modularity and community structure in networks. Proc Natl Acad Sci USA 2006;103(23):8577-82] has been demonstrated using the aforesaid pathways of H. sapiens.

The node-weighted Steiner tree approach to identify elements of cancer-related signaling pathways.

PubMed

Sun, Yahui; Ma, Chenkai; Halgamuge, Saman

2017-12-28

Cancer constitutes a momentous health burden in our society. Critical information on cancer may be hidden in its signaling pathways. However, even though a large amount of money has been spent on cancer research, some critical information on cancer-related signaling pathways still remains elusive. Hence, new works towards a complete understanding of cancer-related signaling pathways will greatly benefit the prevention, diagnosis, and treatment of cancer. We propose the node-weighted Steiner tree approach to identify important elements of cancer-related signaling pathways at the level of proteins. This new approach has advantages over previous approaches since it is fast in processing large protein-protein interaction networks. We apply this new approach to identify important elements of two well-known cancer-related signaling pathways: PI3K/Akt and MAPK. First, we generate a node-weighted protein-protein interaction network using protein and signaling pathway data. Second, we modify and use two preprocessing techniques and a state-of-the-art Steiner tree algorithm to identify a subnetwork in the generated network. Third, we propose two new metrics to select important elements from this subnetwork. On a commonly used personal computer, this new approach takes less than 2 s to identify the important elements of PI3K/Akt and MAPK signaling pathways in a large node-weighted protein-protein interaction network with 16,843 vertices and 1,736,922 edges. We further analyze and demonstrate the significance of these identified elements to cancer signal transduction by exploring previously reported experimental evidences. Our node-weighted Steiner tree approach is shown to be both fast and effective to identify important elements of cancer-related signaling pathways. Furthermore, it may provide new perspectives into the identification of signaling pathways for other human diseases.
A multi-pathway hypothesis for human visual fear signaling

PubMed Central

Silverstein, David N.; Ingvar, Martin

2015-01-01

A hypothesis is proposed for five visual fear signaling pathways in humans, based on an analysis of anatomical connectivity from primate studies and human functional connectvity and tractography from brain imaging studies. Earlier work has identified possible subcortical and cortical fear pathways known as the “low road” and “high road,” which arrive at the amygdala independently. In addition to a subcortical pathway, we propose four cortical signaling pathways in humans along the visual ventral stream. All four of these traverse through the LGN to the visual cortex (VC) and branching off at the inferior temporal area, with one projection directly to the amygdala; another traversing the orbitofrontal cortex; and two others passing through the parietal and then prefrontal cortex, one excitatory pathway via the ventral-medial area and one regulatory pathway via the ventral-lateral area. These pathways have progressively longer propagation latencies and may have progressively evolved with brain development to take advantage of higher-level processing. Using the anatomical path lengths and latency estimates for each of these five pathways, predictions are made for the relative processing times at selective ROIs and arrival at the amygdala, based on the presentation of a fear-relevant visual stimulus. Partial verification of the temporal dynamics of this hypothesis might be accomplished using experimental MEG analysis. Possible experimental protocols are suggested. PMID:26379513
PAMP-induced defense responses in potato require both salicylic acid and jasmonic acid.

PubMed

Halim, Vincentius A; Altmann, Simone; Ellinger, Dorothea; Eschen-Lippold, Lennart; Miersch, Otto; Scheel, Dierk; Rosahl, Sabine

2009-01-01

To elucidate the molecular mechanisms underlying pathogen-associated molecular pattern (PAMP)-induced defense responses in potato (Solanum tuberosum), the role of the signaling compounds salicylic acid (SA) and jasmonic acid (JA) was analyzed. Pep-13, a PAMP from Phytophthora, induces the accumulation of SA, JA and hydrogen peroxide, as well as the activation of defense genes and hypersensitive-like cell death. We have previously shown that SA is required for Pep-13-induced defense responses. To assess the importance of JA, RNA interference constructs targeted at the JA biosynthetic genes, allene oxide cyclase and 12-oxophytodienoic acid reductase, were expressed in transgenic potato plants. In addition, expression of the F-box protein COI1 was reduced by RNA interference. Plants expressing the RNA interference constructs failed to accumulate the respective transcripts in response to wounding or Pep-13 treatment, neither did they contain significant amounts of JA after elicitation. In response to infiltration of Pep-13, the transgenic plants exhibited a highly reduced accumulation of reactive oxygen species as well as reduced hypersensitive cell death. The ability of the JA-deficient plants to accumulate SA suggests that SA accumulation is independent or upstream of JA accumulation. These data show that PAMP responses in potato require both SA and JA and that, in contrast to Arabidopsis, these compounds act in the same signal transduction pathway. Despite their inability to fully respond to PAMP treatment, the transgenic RNA interference plants are not altered in their basal defense against Phytophthora infestans.
Modulation of neurotrophic signaling pathways by polyphenols

PubMed Central

Moosavi, Fatemeh; Hosseini, Razieh; Saso, Luciano; Firuzi, Omidreza

2016-01-01

Polyphenols are an important class of phytochemicals, and several lines of evidence have demonstrated their beneficial effects in the context of a number of pathologies including neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. In this report, we review the studies on the effects of polyphenols on neuronal survival, growth, proliferation and differentiation, and the signaling pathways involved in these neurotrophic actions. Several polyphenols including flavonoids such as baicalein, daidzein, luteolin, and nobiletin as well as nonflavonoid polyphenols such as auraptene, carnosic acid, curcuminoids, and hydroxycinnamic acid derivatives including caffeic acid phentyl ester enhance neuronal survival and promote neurite outgrowth in vitro, a hallmark of neuronal differentiation. Assessment of underlying mechanisms, especially in PC12 neuronal-like cells, reveals that direct agonistic effect on tropomyosin receptor kinase (Trk) receptors, the main receptors of neurotrophic factors including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) explains the action of few polyphenols such as 7,8-dihydroxyflavone. However, several other polyphenolic compounds activate extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)/Akt pathways. Increased expression of neurotrophic factors in vitro and in vivo is the mechanism of neurotrophic action of flavonoids such as scutellarin, daidzein, genistein, and fisetin, while compounds like apigenin and ferulic acid increase cyclic adenosine monophosphate response element-binding protein (CREB) phosphorylation. Finally, the antioxidant activity of polyphenols reflected in the activation of Nrf2 pathway and the consequent upregulation of detoxification enzymes such as heme oxygenase-1 as well as the contribution of these effects to the neurotrophic activity have also been discussed. In conclusion, a better understanding of the neurotrophic effects of polyphenols and
SignaLink 2 - a signaling pathway resource with multi-layered regulatory networks.

PubMed

Fazekas, Dávid; Koltai, Mihály; Türei, Dénes; Módos, Dezső; Pálfy, Máté; Dúl, Zoltán; Zsákai, Lilian; Szalay-Bekő, Máté; Lenti, Katalin; Farkas, Illés J; Vellai, Tibor; Csermely, Péter; Korcsmáros, Tamás

2013-01-18

Signaling networks in eukaryotes are made up of upstream and downstream subnetworks. The upstream subnetwork contains the intertwined network of signaling pathways, while the downstream regulatory part contains transcription factors and their binding sites on the DNA as well as microRNAs and their mRNA targets. Currently, most signaling and regulatory databases contain only a subsection of this network, making comprehensive analyses highly time-consuming and dependent on specific data handling expertise. The need for detailed mapping of signaling systems is also supported by the fact that several drug development failures were caused by undiscovered cross-talk or regulatory effects of drug targets. We previously created a uniformly curated signaling pathway resource, SignaLink, to facilitate the analysis of pathway cross-talks. Here, we present SignaLink 2, which significantly extends the coverage and applications of its predecessor. We developed a novel concept to integrate and utilize different subsections (i.e., layers) of the signaling network. The multi-layered (onion-like) database structure is made up of signaling pathways, their pathway regulators (e.g., scaffold and endocytotic proteins) and modifier enzymes (e.g., phosphatases, ubiquitin ligases), as well as transcriptional and post-transcriptional regulators of all of these components. The user-friendly website allows the interactive exploration of how each signaling protein is regulated. The customizable download page enables the analysis of any user-specified part of the signaling network. Compared to other signaling resources, distinctive features of SignaLink 2 are the following: 1) it involves experimental data not only from humans but from two invertebrate model organisms, C. elegans and D. melanogaster; 2) combines manual curation with large-scale datasets; 3) provides confidence scores for each interaction; 4) operates a customizable download page with multiple file formats (e.g., Bio
Hunger and Satiety Signaling: Modeling Two Hypothalamomedullary Pathways for Energy Homeostasis.

PubMed

Nakamura, Kazuhiro; Nakamura, Yoshiko

2018-06-04

The recent discovery of the medullary circuit driving "hunger responses" - reduced thermogenesis and promoted feeding - has greatly expanded our knowledge on the central neural networks for energy homeostasis. However, how hypothalamic hunger and satiety signals generated under fasted and fed conditions, respectively, control the medullary autonomic and somatic motor mechanisms remains unknown. Here, in reviewing this field, we propose two hypothalamomedullary neural pathways for hunger and satiety signaling. To trigger hunger signaling, neuropeptide Y activates a group of neurons in the paraventricular hypothalamic nucleus (PVH), which then stimulate an excitatory pathway to the medullary circuit to drive the hunger responses. In contrast, melanocortin-mediated satiety signaling activates a distinct group of PVH neurons, which then stimulate a putatively inhibitory pathway to the medullary circuit to counteract the hunger signaling. The medullary circuit likely contains inhibitory and excitatory premotor neurons whose alternate phasic activation generates the coordinated masticatory motor rhythms to promote feeding. © 2018 The Authors. BioEssays Published by WILEY Periodicals, Inc.
How Genetics Has Helped Piece Together the MAPK Signaling Pathway.

PubMed

Ashton-Beaucage, Dariel; Therrien, Marc

2017-01-01

Cells respond to changes in their environment, to developmental cues, and to pathogen aggression through the action of a complex network of proteins. These networks can be decomposed into a multitude of signaling pathways that relay signals from the microenvironment to the cellular components involved in eliciting a specific response. Perturbations in these signaling processes are at the root of multiple pathologies, the most notable of these being cancer. The study of receptor tyrosine kinase (RTK) signaling led to the first description of a mechanism whereby an extracellular signal is transmitted to the nucleus to induce a transcriptional response. Genetic studies conducted in drosophila and nematodes have provided key elements to this puzzle. Here, we briefly discuss the somewhat lesser known contribution of these multicellular organisms to our understanding of what has come to be known as the prototype of signaling pathways. We also discuss the ostensibly much larger network of regulators that has emerged from recent functional genomic investigations of RTK/RAS/ERK signaling.
Auxin Controls Arabidopsis Adventitious Root Initiation by Regulating Jasmonic Acid Homeostasis[W

PubMed Central

Gutierrez, Laurent; Mongelard, Gaëlle; Floková, Kristýna; Păcurar, Daniel I.; Novák, Ondřej; Staswick, Paul; Kowalczyk, Mariusz; Păcurar, Monica; Demailly, Hervé; Geiss, Gaia; Bellini, Catherine

2012-01-01

Vegetative shoot-based propagation of plants, including mass propagation of elite genotypes, is dependent on the development of shoot-borne roots, which are also called adventitious roots. Multiple endogenous and environmental factors control the complex process of adventitious rooting. In the past few years, we have shown that the auxin response factors ARF6 and ARF8, targets of the microRNA miR167, are positive regulators of adventitious rooting, whereas ARF17, a target of miR160, is a negative regulator. We showed that these genes have overlapping expression profiles during adventitious rooting and that they regulate each other’s expression at the transcriptional and posttranscriptional levels by modulating the homeostasis of miR160 and miR167. We demonstrate here that this complex network of transcription factors regulates the expression of three auxin-inducible Gretchen Hagen3 (GH3) genes, GH3.3, GH3.5, and GH3.6, encoding acyl-acid-amido synthetases. We show that these three GH3 genes are required for fine-tuning adventitious root initiation in the Arabidopsis thaliana hypocotyl, and we demonstrate that they act by modulating jasmonic acid homeostasis. We propose a model in which adventitious rooting is an adaptive developmental response involving crosstalk between the auxin and jasmonate regulatory pathways. PMID:22730403
Early biotic stress detection in tomato (Solanum lycopersicum) by BVOC emissions.

PubMed

Kasal-Slavik, Tina; Eschweiler, Julia; Kleist, Einhard; Mumm, Roland; Goldbach, Heiner E; Schouten, Alexander; Wildt, Jürgen

2017-12-01

We investigated impacts of early and mild biotic stress on Biogenic Volatile Organic Compounds (BVOC) emissions from tomato in order to test their potential for early (biotic) stress detection. Tomato plants were exposed to two common fungal pathogens, Botrytis cinerea and Oidium neolycopesici and the sap-sucking aphid Myzus persicae. Furthermore, plants were exposed to methyl jasmonate (MeJA) in order to identify BVOC emissions related to activation of jasmonic acid (JA) signalling pathway. These emissions where then used as a reference for identifying active JA signalling pathway in plants at early stages of biotic stress. After infection by the necrotrophic fungus B. cinerea, changes in BVOC emissions indicated that tomato plants had predominantly activated the jasmonic acid (JA) signalling pathway. The plants were able to modify their defence pathways in order to overcome fungal infection. When tomato plants were infected with the biotrophic fungus O. neolycopersici, only minor changes in BVOC emissions were observed with additional emissions of the sesquiterpene α-copaene. α-copaene emissions allowed the identification of general biotic stress in the plants, without pinpointing the actual triggered defence pathway. BVOC emissions during M. persicae attack had changed before the occurrence of visual symptoms. Despite low infestation rates, plants emitted methyl salicylate indicating activation of the SA-mediated defence pathway. Copyright © 2017 Elsevier Ltd. All rights reserved.
The Jasmonate-Activated Transcription Factor MdMYC2 Regulates ETHYLENE RESPONSE FACTOR and Ethylene Biosynthetic Genes to Promote Ethylene Biosynthesis during Apple Fruit Ripening.

PubMed

Li, Tong; Xu, Yaxiu; Zhang, Lichao; Ji, Yinglin; Tan, Dongmei; Yuan, Hui; Wang, Aide

2017-06-01

The plant hormone ethylene is critical for ripening in climacteric fruits, including apple ( Malus domestica ). Jasmonate (JA) promotes ethylene biosynthesis in apple fruit, but the underlying molecular mechanism is unclear. Here, we found that JA-induced ethylene production in apple fruit is dependent on the expression of MdACS1 , an ACC synthase gene involved in ethylene biosynthesis. The expression of MdMYC2 , encoding a transcription factor involved in the JA signaling pathway, was enhanced by MeJA treatment in apple fruits, and MdMYC2 directly bound to the promoters of both MdACS1 and the ACC oxidase gene MdACO1 and enhanced their transcription. Furthermore, MdMYC2 bound to the promoter of MdERF3 , encoding a transcription factor involved in the ethylene-signaling pathway, thereby activating MdACS1 transcription. We also found that MdMYC2 interacted with MdERF2, a suppressor of MdERF3 and MdACS1 This protein interaction prevented MdERF2 from interacting with MdERF3 and from binding to the MdACS1 promoter, leading to increased transcription of MdACS1 Collectively, these results indicate that JA promotes ethylene biosynthesis through the regulation of MdERFs and ethylene biosynthetic genes by MdMYC2. © 2017 American Society of Plant Biologists. All rights reserved.
Differential and directional estrogenic signaling pathways induced by enterolignans and their precursors

PubMed Central

Zhu, Yun; Kawaguchi, Kayoko; Kiyama, Ryoiti

2017-01-01

Mammalian lignans or enterolignans are metabolites of plant lignans, an important category of phytochemicals. Although they are known to be associated with estrogenic activity, cell signaling pathways leading to specific cell functions, and especially the differences among lignans, have not been explored. We examined the estrogenic activity of enterolignans and their precursor plant lignans and cell signaling pathways for some cell functions, cell cycle and chemokine secretion. We used DNA microarray-based gene expression profiling in human breast cancer MCF-7 cells to examine the similarities, as well as the differences, among enterolignans, enterolactone and enterodiol, and their precursors, matairesinol, pinoresinol and sesamin. The profiles showed moderate to high levels of correlation (R values: 0.44 to 0.81) with that of estrogen (17β-estradiol or E2). Significant correlations were observed among lignans (R values: 0.77 to 0.97), and the correlations were higher for cell functions related to enzymes, signaling, proliferation and transport. All the enterolignans/precursors examined showed activation of the Erk1/2 and PI3K/Akt pathways, indicating the involvement of rapid signaling through the non-genomic estrogen signaling pathway. However, when their effects on specific cell functions, cell cycle progression and chemokine (MCP-1) secretion were examined, positive effects were observed only for enterolactone, suggesting that signals are given in certain directions at a position closer to cell functions. We hypothesized that, while estrogen signaling is initiated by the enterolignans/precursors examined, their signals are differentially and directionally modulated later in the pathways, resulting in the differences at the cell function level. PMID:28152041
Trypanosoma cruzi Exploits Wnt Signaling Pathway to Promote Its Intracellular Replication in Macrophages.

PubMed

Volpini, Ximena; Ambrosio, Laura F; Fozzatti, Laura; Insfran, Constanza; Stempin, Cinthia C; Cervi, Laura; Motran, Claudia Cristina

2018-01-01

During the acute phase of Trypanosoma cruzi infection, macrophages can act as host cells for the parasites as well as effector cells in the early anti-parasitic immune response. Thus, the targeting of specific signaling pathways could modulate macrophages response to restrict parasite replication and instruct an appropriate adaptive response. Recently, it has become evident that Wnt signaling has immunomodulatory functions during inflammation and infection. Here, we tested the hypothesis that during T. cruzi infection, the activation of Wnt signaling pathway in macrophages plays a role in modulating the inflammatory/tolerogenic response and therefore regulating the control of parasite replication. In this report, we show that early after T. cruzi infection of bone marrow-derived macrophages (BMM), β-catenin was activated and Wnt3a, Wnt5a, and some Frizzled receptors as well as Wnt/β-catenin pathway's target genes were upregulated, with Wnt proteins signaling sustaining the activation of Wnt/β-catenin pathway and then activating the Wnt/Ca +2 pathway. Wnt signaling pathway activation was critical to sustain the parasite's replication in BMM; since the treatments with specific inhibitors of β-catenin transcriptional activation or Wnt proteins secretion limited the parasite replication. Mechanistically, inhibition of Wnt signaling pathway armed BMM to fight against T. cruzi by inducing the production of pro-inflammatory cytokines and indoleamine 2,3-dioxygenase activity and by downregulating arginase activity. Likewise, in vivo pharmacological inhibition of the Wnts' interaction with its receptors controlled the parasite replication and improved the survival of lethally infected mice. It is well established that T. cruzi infection activates a plethora of signaling pathways that ultimately regulate immune mediators to determine the modulation of a defined set of effector functions in macrophages. In this study, we have revealed a new signaling pathway that is
Targeting the Hippo Signaling Pathway for Tissue Regeneration and Cancer Therapy

PubMed Central

Juan, Wen Chun; Hong, Wanjin

2016-01-01

The Hippo signaling pathway is a highly-conserved developmental pathway that plays an essential role in organ size control, tumor suppression, tissue regeneration and stem cell self-renewal. The YES-associated protein (YAP) and the transcriptional co-activator with PDZ-binding motif (TAZ) are two important transcriptional co-activators that are negatively regulated by the Hippo signaling pathway. By binding to transcription factors, especially the TEA domain transcription factors (TEADs), YAP and TAZ induce the expression of growth-promoting genes, which can promote organ regeneration after injury. Therefore, controlled activation of YAP and TAZ can be useful for regenerative medicine. However, aberrant activation of YAP and TAZ due to deregulation of the Hippo pathway or overexpression of YAP/TAZ and TEADs can promote cancer development. Hence, pharmacological inhibition of YAP and TAZ may be a useful approach to treat tumors with high YAP and/or TAZ activity. In this review, we present the mechanisms regulating the Hippo pathway, the role of the Hippo pathway in tissue repair and cancer, as well as a detailed analysis of the different strategies to target the Hippo signaling pathway and the genes regulated by YAP and TAZ for regenerative medicine and cancer therapy. PMID:27589805
[Cell signaling pathways interaction in cellular proliferation: Potential target for therapeutic interventionism].

PubMed

Valdespino-Gómez, Víctor Manuel; Valdespino-Castillo, Patricia Margarita; Valdespino-Castillo, Víctor Edmundo

2015-01-01

Nowadays, cellular physiology is best understood by analysing their interacting molecular components. Proteins are the major components of the cells. Different proteins are organised in the form of functional clusters, pathways or networks. These molecules are ordered in clusters of receptor molecules of extracellular signals, transducers, sensors and biological response effectors. The identification of these intracellular signaling pathways in different cellular types has required a long journey of experimental work. More than 300 intracellular signaling pathways have been identified in human cells. They participate in cell homeostasis processes for structural and functional maintenance. Some of them participate simultaneously or in a nearly-consecutive progression to generate a cellular phenotypic change. In this review, an analysis is performed on the main intracellular signaling pathways that take part in the cellular proliferation process, and the potential use of some components of these pathways as target for therapeutic interventionism are also underlined. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.
Gene Expression Profiling Identifies Downregulation of the Neurotrophin-MAPK Signaling Pathway in Female Diabetic Peripheral Neuropathy Patients.

PubMed

Luo, Lin; Zhou, Wen-Hua; Cai, Jiang-Jia; Feng, Mei; Zhou, Mi; Hu, Su-Pei; Xu, Jin; Ji, Lin-Dan

2017-01-01

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus (DM). It is not diagnosed or managed properly in the majority of patients because its pathogenesis remains controversial. In this study, human whole genome microarrays identified 2898 and 4493 differentially expressed genes (DEGs) in DM and DPN patients, respectively. A further KEGG pathway analysis indicated that DPN and DM share four pathways, including apoptosis, B cell receptor signaling pathway, endocytosis, and Toll-like receptor signaling pathway. The DEGs identified through comparison of DPN and DM were significantly enriched in MAPK signaling pathway, NOD-like receptor signaling pathway, and neurotrophin signaling pathway, while the "neurotrophin-MAPK signaling pathway" was notably downregulated. Seven DEGs from the neurotrophin-MAPK signaling pathway were validated in additional 78 samples, and the results confirmed the initial microarray findings. These findings demonstrated that downregulation of the neurotrophin-MAPK signaling pathway may be the major mechanism of DPN pathogenesis, thus providing a potential approach for DPN treatment.
Signaling Pathways in Leiomyoma: Understanding Pathobiology and Implications for Therapy

PubMed Central

Borahay, Mostafa A; Al-Hendy, Ayman; Kilic, Gokhan S; Boehning, Darren

2015-01-01

Uterine leiomyomas are the most common tumors of the female genital tract, affecting 50% to 70% of females by the age of 50. Despite their prevalence and enormous medical and economic impact, no effective medical treatment is currently available. This is, in part, due to the poor understanding of their underlying pathobiology. Although they are thought to start as a clonal proliferation of a single myometrial smooth muscle cell, these early cytogenetic alterations are considered insufficient for tumor development and additional complex signaling pathway alterations are crucial. These include steroids, growth factors, transforming growth factor-beta (TGF-β)/Smad; wingless-type (Wnt)/β-catenin, retinoic acid, vitamin D, and peroxisome proliferator-activated receptor γ (PPARγ). An important finding is that several of these pathways converge in a summative way. For example, mitogen-activated protein kinase (MAPK) and Akt pathways seem to act as signal integrators, incorporating input from several signaling pathways, including growth factors, estrogen and vitamin D. This underlines the multifactorial origin and complex nature of these tumors. In this review, we aim to dissect these pathways and discuss their interconnections, aberrations and role in leiomyoma pathobiology. We also aim to identify potential targets for development of novel therapeutics. PMID:25879625
Protein C receptor stimulates multiple signaling pathways in breast cancer cells.

PubMed

Wang, Daisong; Liu, Chunye; Wang, Jingqiang; Jia, Yingying; Hu, Xin; Jiang, Hai; Shao, Zhi-Ming; Zeng, Yi Arial

2018-01-26

The protein C receptor (PROCR) has emerged as a stem cell marker in several normal tissues and has also been implicated in tumor progression. However, the functional role of PROCR and the signaling mechanisms downstream of PROCR remain poorly understood. Here, we dissected the PROCR signaling pathways in breast cancer cells. Combining protein array, knockdown, and overexpression methods, we found that PROCR concomitantly activates multiple pathways. We also noted that PROCR-dependent ERK and PI3k-Akt-mTOR signaling pathways proceed through Src kinase and transactivation of insulin-like growth factor 1 receptor (IGF-1R). These pathway activities led to the accumulation of c-Myc and cyclin D1. On the other hand, PROCR-dependent RhoA-ROCK-p38 signaling relied on coagulation factor II thrombin receptor (F2R). We confirmed these findings in primary cells isolated from triple-negative breast cancer-derived xenografts (PDX) that have high expression of PROCR. To the best our knowledge, this is the first comprehensive study of PROCR signaling in breast cancer cells, and its findings also shed light on the molecular mechanisms of PROCR in stem cells in normal tissue. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.
Involvement of nitric oxide in the jasmonate-dependent basal defense against root-knot nematode in tomato plants.

PubMed

Zhou, Jie; Jia, Feifei; Shao, Shujun; Zhang, Huan; Li, Guiping; Xia, Xiaojian; Zhou, Yanhong; Yu, Jingquan; Shi, Kai

2015-01-01

Jasmonic acid (JA) and nitric oxide (NO) are well-characterized signaling molecules in plant defense responses. However, their roles in plant defense against root-knot nematode (RKN, Meloidogyne incognita) infection are largely unknown. In this study, we found that the transcript levels of the JA- and NO-related biosynthetic and signaling component genes were induced after RKN infection. Application of exogenous JA and sodium nitroprusside (SNP; a NO donor) significantly decreased the number of egg masses in tomato roots after RKN infection and partially alleviated RKN-induced decreases in plant fresh weight and net photosynthetic rate. These molecules also alleviated RKN-induced increases in root electrolyte leakage and membrane peroxidation. Importantly, NO scavenger partially inhibited JA-induced RKN defense. The pharmacological inhibition of JA biosynthesis significantly increased the plants' susceptibility to RKNs, which was effectively alleviated by SNP application, showing that NO may be involved in the JA-dependent RKN defense pathway. Furthermore, both JA and SNP induced increases in protease inhibitor 2 (PI2) gene expression after RKN infestation. Silencing of PI2 compromised both JA- and SNP-induced RKN defense responses, suggesting that the PI2 gene mediates JA- and NO-induced defense against RKNs. This work will be important for deepening the understanding of the mechanisms involved in basal defense against RKN attack in plants.
Involvement of nitric oxide in the jasmonate-dependent basal defense against root-knot nematode in tomato plants

PubMed Central

Zhou, Jie; Jia, Feifei; Shao, Shujun; Zhang, Huan; Li, Guiping; Xia, Xiaojian; Zhou, Yanhong; Yu, Jingquan; Shi, Kai

2015-01-01

Jasmonic acid (JA) and nitric oxide (NO) are well-characterized signaling molecules in plant defense responses. However, their roles in plant defense against root-knot nematode (RKN, Meloidogyne incognita) infection are largely unknown. In this study, we found that the transcript levels of the JA- and NO-related biosynthetic and signaling component genes were induced after RKN infection. Application of exogenous JA and sodium nitroprusside (SNP; a NO donor) significantly decreased the number of egg masses in tomato roots after RKN infection and partially alleviated RKN-induced decreases in plant fresh weight and net photosynthetic rate. These molecules also alleviated RKN-induced increases in root electrolyte leakage and membrane peroxidation. Importantly, NO scavenger partially inhibited JA-induced RKN defense. The pharmacological inhibition of JA biosynthesis significantly increased the plants’ susceptibility to RKNs, which was effectively alleviated by SNP application, showing that NO may be involved in the JA-dependent RKN defense pathway. Furthermore, both JA and SNP induced increases in protease inhibitor 2 (PI2) gene expression after RKN infestation. Silencing of PI2 compromised both JA- and SNP-induced RKN defense responses, suggesting that the PI2 gene mediates JA- and NO-induced defense against RKNs. This work will be important for deepening the understanding of the mechanisms involved in basal defense against RKN attack in plants. PMID:25914698
Influence of (9Z)-12-hydroxy-9-dodecenoic acid and methyl jasmonate on plant protein phosphorylation.

PubMed

Tarchevsky, I A; Karimova, F G; Grechkin, A N; Moukhametchina, N U

2000-12-01

The products of the lipoxygenase pathway, methyl jasmonic acid (MeJA) and (9Z)-12-hydroxy-9-dodecenoic acid (HDA), hardly changed the relative level of phosphorylated polypeptides (RLPPs) during 2 h of incubation: 15 and 17 kDa RLPPs were enhanced by HDA, but decreased by MeJA. RLPPs of 73 and 82 kDa were increased by both compounds. MeJA and HDA treatment induced specific and unspecific effects in some RLPPs. It was shown that HDA and MeJA increased protein kinase activity in the presence of 1 microM cAMP.

The ethylene signal transduction pathway in Arabidopsis

NASA Technical Reports Server (NTRS)

Kieber, J. J.; Evans, M. L. (Principal Investigator)

1997-01-01

The gaseous hormone ethylene is an important regulator of plant growth and development. Using a simple response of etiolated seedlings to ethylene as a genetic screen, genes involved in ethylene signal transduction have been identified in Arabidopsis. Analysis of two of these genes that have been cloned reveals that ethylene signalling involves a combination of a protein (ETR1) with similarity to bacterial histidine kinases and a protein (CTR1) with similarity to Raf-1, a protein kinase involved in multiple signalling cascades in eukaryotic cells. Several lines of investigation provide compelling evidence that ETR1 encodes an ethylene receptor. For the first time there is a glimpse of the molecular circuitry underlying the signal transduction pathway for a plant hormone.
Application of Petri net based analysis techniques to signal transduction pathways.

PubMed

Sackmann, Andrea; Heiner, Monika; Koch, Ina

2006-11-02

Signal transduction pathways are usually modelled using classical quantitative methods, which are based on ordinary differential equations (ODEs). However, some difficulties are inherent in this approach. On the one hand, the kinetic parameters involved are often unknown and have to be estimated. With increasing size and complexity of signal transduction pathways, the estimation of missing kinetic data is not possible. On the other hand, ODEs based models do not support any explicit insights into possible (signal-) flows within the network. Moreover, a huge amount of qualitative data is available due to high-throughput techniques. In order to get information on the systems behaviour, qualitative analysis techniques have been developed. Applications of the known qualitative analysis methods concern mainly metabolic networks. Petri net theory provides a variety of established analysis techniques, which are also applicable to signal transduction models. In this context special properties have to be considered and new dedicated techniques have to be designed. We apply Petri net theory to model and analyse signal transduction pathways first qualitatively before continuing with quantitative analyses. This paper demonstrates how to build systematically a discrete model, which reflects provably the qualitative biological behaviour without any knowledge of kinetic parameters. The mating pheromone response pathway in Saccharomyces cerevisiae serves as case study. We propose an approach for model validation of signal transduction pathways based on the network structure only. For this purpose, we introduce the new notion of feasible t-invariants, which represent minimal self-contained subnets being active under a given input situation. Each of these subnets stands for a signal flow in the system. We define maximal common transition sets (MCT-sets), which can be used for t-invariant examination and net decomposition into smallest biologically meaningful functional units. The
Update on Staphylococcal Superantigen-Induced Signaling Pathways and Therapeutic Interventions

PubMed Central

Krakauer, Teresa

2013-01-01

Staphylococcal enterotoxin B (SEB) and related bacterial toxins cause diseases in humans and laboratory animals ranging from food poisoning, acute lung injury to toxic shock. These superantigens bind directly to the major histocompatibility complex class II molecules on antigen-presenting cells and specific Vβ regions of T-cell receptors (TCR), resulting in rapid hyper-activation of the host immune system. In addition to TCR and co-stimulatory signals, proinflammatory mediators activate signaling pathways culminating in cell-stress response, activation of NFκB and mammalian target of rapamycin (mTOR). This article presents a concise review of superantigen-activated signaling pathways and focuses on the therapeutic challenges against bacterial superantigens. PMID:24064719
Signaling Pathways Involved in the Regulation of mRNA Translation

PubMed Central

2018-01-01

ABSTRACT Translation is a key step in the regulation of gene expression and one of the most energy-consuming processes in the cell. In response to various stimuli, multiple signaling pathways converge on the translational machinery to regulate its function. To date, the roles of phosphoinositide 3-kinase (PI3K)/AKT and the mitogen-activated protein kinase (MAPK) pathways in the regulation of translation are among the best understood. Both pathways engage the mechanistic target of rapamycin (mTOR) to regulate a variety of components of the translational machinery. While these pathways regulate protein synthesis in homeostasis, their dysregulation results in aberrant translation leading to human diseases, including diabetes, neurological disorders, and cancer. Here we review the roles of the PI3K/AKT and MAPK pathways in the regulation of mRNA translation. We also highlight additional signaling mechanisms that have recently emerged as regulators of the translational apparatus. PMID:29610153
AKAP-Lbc mobilizes a cardiac hypertrophy signaling pathway.

PubMed

Carnegie, Graeme K; Soughayer, Joseph; Smith, F Donelson; Pedroja, Benjamin S; Zhang, Fang; Diviani, Dario; Bristow, Michael R; Kunkel, Maya T; Newton, Alexandra C; Langeberg, Lorene K; Scott, John D

2008-10-24

Elevated catecholamines in the heart evoke transcriptional activation of the Myocyte Enhancer Factor (MEF) pathway to induce a cellular response known as pathological myocardial hypertrophy. We have discovered that the A-Kinase Anchoring Protein (AKAP)-Lbc is upregulated in hypertrophic cardiomyocytes. It coordinates activation and movement of signaling proteins that initiate MEF2-mediated transcriptional reprogramming events. Live-cell imaging, fluorescent kinase activity reporters, and RNA interference techniques show that AKAP-Lbc couples activation of protein kinase D (PKD) with the phosphorylation-dependent nuclear export of the class II histone deacetylase HDAC5. These studies uncover a role for AKAP-Lbc in which increased expression of the anchoring protein selectively amplifies a signaling pathway that drives cardiac myocytes toward a pathophysiological outcome.
Dissecting Nck/Dock signaling pathways in Drosophila visual system.

PubMed

Rao, Yong

2005-01-01

The establishment of neuronal connections during embryonic development requires the precise guidance and targeting of the neuronal growth cone, an expanded cellular structure at the leading tip of a growing axon. The growth cone contains sophisticated signaling systems that allow the rapid communication between guidance receptors and the actin cytoskeleton in generating directed motility. Previous studies demonstrated a specific role for the Nck/Dock SH2/SH3 adapter protein in photoreceptor (R cell) axon guidance and target recognition in the Drosophila visual system, suggesting strongly that Nck/Dock is one of the long-sought missing links between cell surface receptors and the actin cytoskeleton. In this review, I discuss the recent progress on dissecting the Nck/Dock signaling pathways in R-cell growth cones. These studies have identified additional key components of the Nck/Dock signaling pathways for linking the receptor signaling to the remodeling of the actin cytoskeleton in controlling growth-cone motility.
Dissecting Nck/Dock Signaling Pathways in Drosophila Visual System

PubMed Central

2005-01-01

The establishment of neuronal connections during embryonic development requires the precise guidance and targeting of the neuronal growth cone, an expanded cellular structure at the leading tip of a growing axon. The growth cone contains sophisticated signaling systems that allow the rapid communication between guidance receptors and the actin cytoskeleton in generating directed motility. Previous studies demonstrated a specific role for the Nck/Dock SH2/SH3 adapter protein in photoreceptor (R cell) axon guidance and target recognition in the Drosophila visual system, suggesting strongly that Nck/Dock is one of the long-sought missing links between cell surface receptors and the actin cytoskeleton. In this review, I discuss the recent progress on dissecting the Nck/Dock signaling pathways in R-cell growth cones. These studies have identified additional key components of the Nck/Dock signaling pathways for linking the receptor signaling to the remodeling of the actin cytoskeleton in controlling growth-cone motility. PMID:15951852
Dissecting the Transcriptional Response to Elicitors in Vitis vinifera Cells

PubMed Central

Belchí-Navarro, Sarai; Bru, Roque; Martínez-Zapater, José M.; Lijavetzky, Diego; Pedreño, María A.

2014-01-01

The high effectiveness of cyclic oligosaccharides like cyclodextrins in the production of trans-resveratrol in Vitis vinifera cell cultures is enhanced in the presence of methyl jasmonate. In order to dissect the basis of the interactions among the elicitation responses triggered by these two compounds, a transcriptional analysis of grapevine cell cultures treated with cyclodextrins and methyl jasmonate separately or in combination was carried out. The results showed that the activation of genes encoding enzymes from phenylpropanoid and stilbene biosynthesis induced by cyclodextrins alone was partially enhanced in the presence of methyl jasmonate, which correlated with their effects on trans-resveratrol production. In addition, protein translation and cell cycle regulation were more highly repressed in cells treated with cyclodextrins than in those treated with methyl jasmonate, and this response was enhanced in the combined treatment. Ethylene signalling was activated by all treatments, while jasmonate signalling and salicylic acid conjugation were activated only in the presence of methyl jasmonate and cyclodextrins, respectively. Moreover, the combined treatment resulted in a crosstalk between the signalling cascades activated by cyclodextrins and methyl jasmonate, which, in turn, provoked the activation of additional regulatory pathways involving the up-regulation of MYB15, NAC and WRKY transcription factors, protein kinases and calcium signal transducers. All these results suggest that both elicitors cause an activation of the secondary metabolism in detriment of basic cell processes like the primary metabolism or cell division. Crosstalk between cyclodextrins and methyl jasmonate-induced signalling provokes an intensification of these responses resulting in a greater trans-resveratrol production. PMID:25314001
Gene Expression Profiling Identifies Downregulation of the Neurotrophin-MAPK Signaling Pathway in Female Diabetic Peripheral Neuropathy Patients

PubMed Central

Luo, Lin; Zhou, Wen-Hua; Cai, Jiang-Jia; Feng, Mei; Zhou, Mi; Hu, Su-Pei

2017-01-01

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus (DM). It is not diagnosed or managed properly in the majority of patients because its pathogenesis remains controversial. In this study, human whole genome microarrays identified 2898 and 4493 differentially expressed genes (DEGs) in DM and DPN patients, respectively. A further KEGG pathway analysis indicated that DPN and DM share four pathways, including apoptosis, B cell receptor signaling pathway, endocytosis, and Toll-like receptor signaling pathway. The DEGs identified through comparison of DPN and DM were significantly enriched in MAPK signaling pathway, NOD-like receptor signaling pathway, and neurotrophin signaling pathway, while the “neurotrophin-MAPK signaling pathway” was notably downregulated. Seven DEGs from the neurotrophin-MAPK signaling pathway were validated in additional 78 samples, and the results confirmed the initial microarray findings. These findings demonstrated that downregulation of the neurotrophin-MAPK signaling pathway may be the major mechanism of DPN pathogenesis, thus providing a potential approach for DPN treatment. PMID:28900628
Evaluation of Signaling Pathways Involved in γ-Globin Gene Induction Using Fetal Hemoglobin Inducer Drugs.

PubMed

Rahim, Fakher; Allahmoradi, Hossein; Salari, Fatemeh; Shahjahani, Mohammad; Fard, Ali Dehghani; Hosseini, Seyed Ahmad; Mousakhani, Hadi

2013-01-01

Potent induction of fetal hemoglobin (HbF) production results in alleviating the complications of β-thalassemia and sickle cell disease (SCD). HbF inducer agents can trigger several molecular signaling pathways critical for erythropoiesis. Janus kinase/Signal transducer and activator of transcription (JAK/STAT), mitogen activated protein kinas (MAPK) and Phosphoinositide 3-kinase (PI3K) are considered as main signaling pathways, which may play a significant role in HbF induction. All these signaling pathways are triggered by erythropoietin (EPO) as the main growth factor inducing erythroid differentiation, when it binds to its cell surface receptor, erythropoietin receptor (EPO-R) HbF inducer agents have been shown to upregulate HbF production level by triggering certain signaling pathways. As a result, understanding the pivotal signaling pathways influencing HbF induction leads to effective upregulation of HbF. In this mini review article, we try to consider the correlation between HbF inducer agents and their molecular mechanisms of γ-globin upregulation. Several studies suggest that activating P38 MAPK, RAS and STAT5 signaling pathways result in efficient HbF induction. Nevertheless, the role of other erythroid signaling pathways in HbF induction seems to be indispensible and should be emphasized.
Controversies in cancer stem cells: targeting embryonic signaling pathways.

PubMed

Takebe, Naoko; Ivy, S Percy

2010-06-15

Selectively targeting cancer stem cells (CSC) or tumor-initiating cells (TIC; from this point onward referred to as CSCs) with novel agents is a rapidly emerging field of oncology. Our knowledge of CSCs and their niche microenvironments remains a nascent field. CSC's critical dependence upon self-renewal makes these regulatory signaling pathways ripe for the development of experimental therapeutic agents. Investigational agents targeting the Notch, Hedgehog, and Wnt pathways are currently in late preclinical development stages, with some early phase 1-2 testing in human subjects. This series of articles will provide an overview and summary of the current state of knowledge of CSCs, their interactive microenvironment, and how they may serve as important targets for antitumor therapies. We also examine the scope and stage of development of early experimental agents that specifically target these highly conserved embryonic signaling pathways. (c) 2010 AACR.
Berberine inhibits enterovirus 71 replication by downregulating the MEK/ERK signaling pathway and autophagy.

PubMed

Wang, Huiqiang; Li, Ke; Ma, Linlin; Wu, Shuo; Hu, Jin; Yan, Haiyan; Jiang, Jiandong; Li, Yuhuan

2017-01-11

The MEK-ERK signaling pathway and autophagy play an important role for enterovirus71(EV71) replication. Inhibition of MEK-ERK signaling pathway and autophagy is shown to impair EV71 replication. Berberine (BBR), an isoquinoline alkaloid isolated from Berberis vulgaris L., has been reported to have ability to regulate this signaling pathway and autophagy. Herein, we want to determine whether berberine can inhibit EV71 infection by downregulating the MEK/ERK signaling pathway and autophagy. The antiviral effect of berberine was determined by cytopathic effect (CPE) assay, western blotting assay and qRT-PCR assay. The mechanism of BBR anti-virus was determined by western blotting assay and immunofluorescence assay. We showed that berberine does-dependently reduced EV71 RNA and protein synthesis, which was, at least in part, the result of inhibition of activation of MEK/ERK signaling pathway. Furthermore, we found that berberine suppressed the EV71-induced autophagy by activating AKT protein and inhibiting the phosphorylation of JNK and PI3KIII. BBR inhibited EV71 replication by downregulating autophagy and MEK/ERK signaling pathway. These findings suggest that BBR may be a potential agent or supplement against EV71 infection.
Quantification of growth factor signaling and pathway cross talk by live-cell imaging

PubMed Central

Gross, Sean M.

2017-01-01

Peptide growth factors stimulate cellular responses through activation of their transmembrane receptors. Multiple intracellular signaling cascades are engaged following growth factor–receptor binding, leading to short- and long-term biological effects. Each receptor-activated signaling pathway does not act in isolation but rather interacts at different levels with other pathways to shape signaling networks that are distinctive for each growth factor. To gain insights into the specifics of growth factor-regulated interactions among different signaling cascades, we developed a HeLa cell line stably expressing fluorescent live-cell imaging reporters that are readouts for two major growth factor-stimulated pathways, Ras–Raf–Mek–ERK and phosphatidylinositol (PI) 3-kinase–Akt. Incubation of cells with epidermal growth factor (EGF) resulted in rapid, robust, and sustained ERK signaling but shorter-term activation of Akt. In contrast, hepatocyte growth factor induced sustained Akt signaling but weak and short-lived ERK activity, and insulin-like growth factor-I stimulated strong long-term Akt responses but negligible ERK signaling. To address potential interactions between signaling pathways, we employed specific small-molecule inhibitors. In cells incubated with EGF or platelet-derived growth factor-AA, Raf activation and the subsequent stimulation of ERK reduced Akt signaling, whereas Mek inhibition, which blocked ERK activation, enhanced Akt and turned transient effects into sustained responses. Our results reveal that individual growth factors initiate signaling cascades that vary markedly in strength and duration and demonstrate in living cells the dramatic effects of cross talk from Raf and Mek to PI 3-kinase and Akt. Our data further indicate how specific growth factors can encode distinct cellular behaviors by promoting complex interactions among signaling pathways. PMID:28100485
Arabidopsis Class I and Class II TCP Transcription Factors Regulate Jasmonic Acid Metabolism and Leaf Development Antagonistically1[C][W

PubMed Central

Danisman, Selahattin; van der Wal, Froukje; Dhondt, Stijn; Waites, Richard; de Folter, Stefan; Bimbo, Andrea; van Dijk, Aalt DJ; Muino, Jose M.; Cutri, Lucas; Dornelas, Marcelo C.; Angenent, Gerco C.; Immink, Richard G.H.

2012-01-01

TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR1 (TCP) transcription factors control developmental processes in plants. The 24 TCP transcription factors encoded in the Arabidopsis (Arabidopsis thaliana) genome are divided into two classes, class I and class II TCPs, which are proposed to act antagonistically. We performed a detailed phenotypic analysis of the class I tcp20 mutant, showing an increase in leaf pavement cell sizes in 10-d-old seedlings. Subsequently, a glucocorticoid receptor induction assay was performed, aiming to identify potential target genes of the TCP20 protein during leaf development. The LIPOXYGENASE2 (LOX2) and class I TCP9 genes were identified as TCP20 targets, and binding of TCP20 to their regulatory sequences could be confirmed by chromatin immunoprecipitation analyses. LOX2 encodes for a jasmonate biosynthesis gene, which is also targeted by class II TCP proteins that are under the control of the microRNA JAGGED AND WAVY (JAW), although in an antagonistic manner. Mutation of TCP9, the second identified TCP20 target, resulted in increased pavement cell sizes during early leaf developmental stages. Analysis of senescence in the single tcp9 and tcp20 mutants and the tcp9tcp20 double mutants showed an earlier onset of this process in comparison with wild-type control plants in the double mutant only. Both the cell size and senescence phenotypes are opposite to the known class II TCP mutant phenotype in JAW plants. Altogether, these results point to an antagonistic function of class I and class II TCP proteins in the control of leaf development via the jasmonate signaling pathway. PMID:22718775
Wnt signal transduction pathways: modules, development and evolution.

PubMed

Nayak, Losiana; Bhattacharyya, Nitai P; De, Rajat K

2016-08-01

Wnt signal transduction pathway (Wnt STP) is a crucial intracellular pathway mainly due to its participation in important biological processes, functions, and diseases, i.e., embryonic development, stem-cell management, and human cancers among others. This is why Wnt STP is one of the highest researched signal transduction pathways. Study and analysis of its origin, expansion and gradual development to the present state as found in humans is one aspect of Wnt research. The pattern of development and evolution of the Wnt STP among various species is not clear till date. A phylogenetic tree created from Wnt STPs of multiple species may address this issue. In this respect, we construct a phylogenetic tree from modules of Wnt STPs of diverse species. We term it as the 'Module Tree'. A module is nothing but a self-sufficient minimally-dependent subset of the original Wnt STP. Authenticity of the module tree is tested by comparing it with the two reference trees. The module tree performs better than an alternative phylogenetic tree constructed from pathway topology of Wnt STPs. Moreover, an evolutionary emergence pattern of the Wnt gene family is created and the module tree is tallied with it to showcase the significant resemblances.
Non Linear Programming (NLP) Formulation for Quantitative Modeling of Protein Signal Transduction Pathways

PubMed Central

Morris, Melody K.; Saez-Rodriguez, Julio; Lauffenburger, Douglas A.; Alexopoulos, Leonidas G.

2012-01-01

Modeling of signal transduction pathways plays a major role in understanding cells' function and predicting cellular response. Mathematical formalisms based on a logic formalism are relatively simple but can describe how signals propagate from one protein to the next and have led to the construction of models that simulate the cells response to environmental or other perturbations. Constrained fuzzy logic was recently introduced to train models to cell specific data to result in quantitative pathway models of the specific cellular behavior. There are two major issues in this pathway optimization: i) excessive CPU time requirements and ii) loosely constrained optimization problem due to lack of data with respect to large signaling pathways. Herein, we address both issues: the former by reformulating the pathway optimization as a regular nonlinear optimization problem; and the latter by enhanced algorithms to pre/post-process the signaling network to remove parts that cannot be identified given the experimental conditions. As a case study, we tackle the construction of cell type specific pathways in normal and transformed hepatocytes using medium and large-scale functional phosphoproteomic datasets. The proposed Non Linear Programming (NLP) formulation allows for fast optimization of signaling topologies by combining the versatile nature of logic modeling with state of the art optimization algorithms. PMID:23226239
Non Linear Programming (NLP) formulation for quantitative modeling of protein signal transduction pathways.

PubMed

Mitsos, Alexander; Melas, Ioannis N; Morris, Melody K; Saez-Rodriguez, Julio; Lauffenburger, Douglas A; Alexopoulos, Leonidas G

2012-01-01

Modeling of signal transduction pathways plays a major role in understanding cells' function and predicting cellular response. Mathematical formalisms based on a logic formalism are relatively simple but can describe how signals propagate from one protein to the next and have led to the construction of models that simulate the cells response to environmental or other perturbations. Constrained fuzzy logic was recently introduced to train models to cell specific data to result in quantitative pathway models of the specific cellular behavior. There are two major issues in this pathway optimization: i) excessive CPU time requirements and ii) loosely constrained optimization problem due to lack of data with respect to large signaling pathways. Herein, we address both issues: the former by reformulating the pathway optimization as a regular nonlinear optimization problem; and the latter by enhanced algorithms to pre/post-process the signaling network to remove parts that cannot be identified given the experimental conditions. As a case study, we tackle the construction of cell type specific pathways in normal and transformed hepatocytes using medium and large-scale functional phosphoproteomic datasets. The proposed Non Linear Programming (NLP) formulation allows for fast optimization of signaling topologies by combining the versatile nature of logic modeling with state of the art optimization algorithms.
Herpes simplex virus triggers activation of calcium-signaling pathways

PubMed Central

Cheshenko, Natalia; Del Rosario, Brian; Woda, Craig; Marcellino, Daniel; Satlin, Lisa M.; Herold, Betsy C.

2003-01-01

The cellular pathways required for herpes simplex virus (HSV) invasion have not been defined. To test the hypothesis that HSV entry triggers activation of Ca2+-signaling pathways, the effects on intracellular calcium concentration ([Ca2+]i) after exposure of cells to HSV were examined. Exposure to virus results in a rapid and transient increase in [Ca2+]i. Pretreatment of cells with pharmacological agents that block release of inositol 1,4,5-triphosphate (IP3)–sensitive endoplasmic reticulum stores abrogates the response. Moreover, treatment of cells with these pharmacological agents inhibits HSV infection and prevents focal adhesion kinase (FAK) phosphorylation, which occurs within 5 min after viral infection. Viruses deleted in glycoprotein L or glycoprotein D, which bind but do not penetrate, fail to induce a [Ca2+]i response or trigger FAK phosphorylation. Together, these results support a model for HSV infection that requires activation of IP3-responsive Ca2+-signaling pathways and that is associated with FAK phosphorylation. Defining the pathway of viral invasion may lead to new targets for anti-viral therapy. PMID:14568989
Transcriptome Analysis of the Signalling Networks in Coronatine-Induced Secondary Laticifer Differentiation from Vascular Cambia in Rubber Trees

PubMed Central

Wu, Shaohua; Zhang, Shixin; Chao, Jinquan; Deng, Xiaomin; Chen, Yueyi; Shi, Minjing; Tian, Wei-Min

2016-01-01

The secondary laticifer in rubber tree (Hevea brasiliensis Muell. Arg.) is a specific tissue within the secondary phloem. This tissue differentiates from the vascular cambia, and its function is natural rubber biosynthesis and storage. Given that jasmonates play a pivotal role in secondary laticifer differentiation, we established an experimental system with jasmonate (JA) mimic coronatine (COR) for studying the secondary laticifer differentiation: in this system, differentiation occurs within five days of the treatment of epicormic shoots with COR. In the present study, the experimental system was used to perform transcriptome sequencing and gene expression analysis. A total of 67,873 unigenes were assembled, and 50,548 unigenes were mapped at least in one public database. Of these being annotated unigenes, 15,780 unigenes were differentially expressed early after COR treatment, and 19,824 unigenes were differentially expressed late after COR treatment. At the early stage, 8,646 unigenes were up-regulated, while 7,134 unigenes were down-regulated. At the late stage, the numbers of up- and down-regulated unigenes were 7,711 and 12,113, respectively. The annotation data and gene expression analysis of the differentially expressed unigenes suggest that JA-mediated signalling, Ca2+ signal transduction and the CLAVATA-MAPK-WOX signalling pathway may be involved in regulating secondary laticifer differentiation in rubber trees. PMID:27808245
Construction of large signaling pathways using an adaptive perturbation approach with phosphoproteomic data.

PubMed

Melas, Ioannis N; Mitsos, Alexander; Messinis, Dimitris E; Weiss, Thomas S; Rodriguez, Julio-Saez; Alexopoulos, Leonidas G

2012-04-01

Construction of large and cell-specific signaling pathways is essential to understand information processing under normal and pathological conditions. On this front, gene-based approaches offer the advantage of large pathway exploration whereas phosphoproteomic approaches offer a more reliable view of pathway activities but are applicable to small pathway sizes. In this paper, we demonstrate an experimentally adaptive approach to construct large signaling pathways from phosphoproteomic data within a 3-day time frame. Our approach--taking advantage of the fast turnaround time of the xMAP technology--is carried out in four steps: (i) screen optimal pathway inducers, (ii) select the responsive ones, (iii) combine them in a combinatorial fashion to construct a phosphoproteomic dataset, and (iv) optimize a reduced generic pathway via an Integer Linear Programming formulation. As a case study, we uncover novel players and their corresponding pathways in primary human hepatocytes by interrogating the signal transduction downstream of 81 receptors of interest and constructing a detailed model for the responsive part of the network comprising 177 species (of which 14 are measured) and 365 interactions.

Dissecting Cell-Fate Determination Through Integrated Mathematical Modeling of the ERK/MAPK Signaling Pathway.

PubMed

Shin, Sung-Young; Nguyen, Lan K

2017-01-01

The past three decades have witnessed an enormous progress in the elucidation of the ERK/MAPK signaling pathway and its involvement in various cellular processes. Because of its importance and complex wiring, the ERK pathway has been an intensive subject for mathematical modeling, which facilitates the unraveling of key dynamic properties and behaviors of the pathway. Recently, however, it became evident that the pathway does not act in isolation but closely interacts with many other pathways to coordinate various cellular outcomes under different pathophysiological contexts. This has led to an increasing number of integrated, large-scale models that link the ERK pathway to other functionally important pathways. In this chapter, we first discuss the essential steps in model development and notable models of the ERK pathway. We then use three examples of integrated, multipathway models to investigate how crosstalk of ERK signaling with other pathways regulates cell-fate decision-making in various physiological and disease contexts. Specifically, we focus on ERK interactions with the phosphoinositide-3 kinase (PI3K), c-Jun N-terminal kinase (JNK), and β-adrenergic receptor (β-AR) signaling pathways. We conclude that integrated modeling in combination with wet-lab experimentation have been and will be instrumental in gaining an in-depth understanding of ERK signaling in multiple biological contexts.
Eliminating Cancer Stem Cells by Targeting Embryonic Signaling Pathways.

PubMed

Oren, Ohad; Smith, B Douglas

2017-02-01

Dramatic advances have been made in the understanding of cancer over the past decade. Prime among those are better appreciation of the biology of cancer and the development of targeted therapies. Despite these improvements, however, most tumors remain refractory to anti-cancer medications and frequently recur. Cancer Stem Cells (CSCs), which in some cases express markers of pluripotency (e.g., Oct-4), share many of the molecular features of normal stem cells. These cells have been hypothesised to play a role in tumor resistance and relapse. They exhibit dependence on many primitive regulatory pathways and may be best viewed in the context of embryonic signaling pathways. In this article, we review important embryonic signaling cascades and their differential expression in CSCs. We also discuss these pathways as actionable targets for novel therapies in hopes that eliminating cancer stem cells will lead to an improvement in overall survival for patients.
Application of Petri net based analysis techniques to signal transduction pathways

PubMed Central

Sackmann, Andrea; Heiner, Monika; Koch, Ina

2006-01-01

Background Signal transduction pathways are usually modelled using classical quantitative methods, which are based on ordinary differential equations (ODEs). However, some difficulties are inherent in this approach. On the one hand, the kinetic parameters involved are often unknown and have to be estimated. With increasing size and complexity of signal transduction pathways, the estimation of missing kinetic data is not possible. On the other hand, ODEs based models do not support any explicit insights into possible (signal-) flows within the network. Moreover, a huge amount of qualitative data is available due to high-throughput techniques. In order to get information on the systems behaviour, qualitative analysis techniques have been developed. Applications of the known qualitative analysis methods concern mainly metabolic networks. Petri net theory provides a variety of established analysis techniques, which are also applicable to signal transduction models. In this context special properties have to be considered and new dedicated techniques have to be designed. Methods We apply Petri net theory to model and analyse signal transduction pathways first qualitatively before continuing with quantitative analyses. This paper demonstrates how to build systematically a discrete model, which reflects provably the qualitative biological behaviour without any knowledge of kinetic parameters. The mating pheromone response pathway in Saccharomyces cerevisiae serves as case study. Results We propose an approach for model validation of signal transduction pathways based on the network structure only. For this purpose, we introduce the new notion of feasible t-invariants, which represent minimal self-contained subnets being active under a given input situation. Each of these subnets stands for a signal flow in the system. We define maximal common transition sets (MCT-sets), which can be used for t-invariant examination and net decomposition into smallest biologically
Quantification of growth factor signaling and pathway cross talk by live-cell imaging.

PubMed

Gross, Sean M; Rotwein, Peter

2017-03-01

Peptide growth factors stimulate cellular responses through activation of their transmembrane receptors. Multiple intracellular signaling cascades are engaged following growth factor-receptor binding, leading to short- and long-term biological effects. Each receptor-activated signaling pathway does not act in isolation but rather interacts at different levels with other pathways to shape signaling networks that are distinctive for each growth factor. To gain insights into the specifics of growth factor-regulated interactions among different signaling cascades, we developed a HeLa cell line stably expressing fluorescent live-cell imaging reporters that are readouts for two major growth factor-stimulated pathways, Ras-Raf-Mek-ERK and phosphatidylinositol (PI) 3-kinase-Akt. Incubation of cells with epidermal growth factor (EGF) resulted in rapid, robust, and sustained ERK signaling but shorter-term activation of Akt. In contrast, hepatocyte growth factor induced sustained Akt signaling but weak and short-lived ERK activity, and insulin-like growth factor-I stimulated strong long-term Akt responses but negligible ERK signaling. To address potential interactions between signaling pathways, we employed specific small-molecule inhibitors. In cells incubated with EGF or platelet-derived growth factor-AA, Raf activation and the subsequent stimulation of ERK reduced Akt signaling, whereas Mek inhibition, which blocked ERK activation, enhanced Akt and turned transient effects into sustained responses. Our results reveal that individual growth factors initiate signaling cascades that vary markedly in strength and duration and demonstrate in living cells the dramatic effects of cross talk from Raf and Mek to PI 3-kinase and Akt. Our data further indicate how specific growth factors can encode distinct cellular behaviors by promoting complex interactions among signaling pathways. Copyright © 2017 the American Physiological Society.
Jasmonic Acid Enhances Al-Induced Root Growth Inhibition.

PubMed

Yang, Zhong-Bao; He, Chunmei; Ma, Yanqi; Herde, Marco; Ding, Zhaojun

2017-02-01

Phytohormones such as ethylene and auxin are involved in the regulation of the aluminum (Al)-induced root growth inhibition. Although jasmonate (JA) has been reported to play a crucial role in the regulation of root growth and development in response to environmental stresses through interplay with ethylene and auxin, its role in the regulation of root growth response to Al stress is not yet known. In an attempt to elucidate the role of JA, we found that exogenous application of JA enhanced the Al-induced root growth inhibition. Furthermore, phenotype analysis with mutants defective in either JA biosynthesis or signaling suggests that JA is involved in the regulation of Al-induced root growth inhibition. The expression of the JA receptor CORONATINE INSENSITIVE1 (COI1) and the key JA signaling regulator MYC2 was up-regulated in response to Al stress in the root tips. This process together with COI1-mediated Al-induced root growth inhibition under Al stress was controlled by ethylene but not auxin. Transcriptomic analysis revealed that many responsive genes under Al stress were regulated by JA signaling. The differential responsive of microtubule organization-related genes between the wild-type and coi1-2 mutant is consistent with the changed depolymerization of cortical microtubules in coi1 under Al stress. In addition, ALMT-mediated malate exudation and thus Al exclusion from roots in response to Al stress was also regulated by COI1-mediated JA signaling. Together, this study suggests that root growth inhibition is regulated by COI1-mediated JA signaling independent from auxin signaling and provides novel insights into the phytohormone-mediated root growth inhibition in response to Al stress. © 2017 American Society of Plant Biologists. All Rights Reserved.
Sex and hedgehog: roles of genes in the hedgehog signaling pathway in mammalian sexual differentiation.

PubMed

Franco, Heather L; Yao, Humphrey H-C

2012-01-01

The chromosome status of the mammalian embryo initiates a multistage process of sexual development in which the bipotential reproductive system establishes itself as either male or female. These events are governed by intricate cell-cell and interorgan communication that is regulated by multiple signaling pathways. The hedgehog signaling pathway was originally identified for its key role in the development of Drosophila, but is now recognized as a critical developmental regulator in many species, including humans. In addition to its developmental roles, the hedgehog signaling pathway also modulates adult organ function, and misregulation of this pathway often leads to diseases, such as cancer. The hedgehog signaling pathway acts through its morphogenetic ligands that signal from ligand-producing cells to target cells over a specified distance. The target cells then respond in a graded manner based on the concentration of the ligands that they are exposed to. Through this unique mechanism of action, the hedgehog signaling pathway elicits cell fate determination, epithelial-mesenchymal interactions, and cellular homeostasis. Here, we review current findings on the roles of hedgehog signaling in the sexually dimorphic development of the reproductive organs with an emphasis on mammals and comparative evidence in other species.
Metformin targets multiple signaling pathways in cancer.

PubMed

Lei, Yong; Yi, Yanhua; Liu, Yang; Liu, Xia; Keller, Evan T; Qian, Chao-Nan; Zhang, Jian; Lu, Yi

2017-01-26

Metformin, an inexpensive and well-tolerated oral agent commonly used in the first-line treatment of type 2 diabetes, has become the focus of intense research as a candidate anticancer agent. Here, we discuss the potential of metformin in cancer therapeutics, particularly its functions in multiple signaling pathways, including AMP-activated protein kinase, mammalian target of rapamycin, insulin-like growth factor, c-Jun N-terminal kinase/mitogen-activated protein kinase (p38 MAPK), human epidermal growth factor receptor-2, and nuclear factor kappaB pathways. In addition, cutting-edge targeting of cancer stem cells by metformin is summarized.
Muscle redox signalling pathways in exercise. Role of antioxidants.

PubMed

Mason, Shaun A; Morrison, Dale; McConell, Glenn K; Wadley, Glenn D

2016-09-01

Recent research highlights the importance of redox signalling pathway activation by contraction-induced reactive oxygen species (ROS) and nitric oxide (NO) in normal exercise-related cellular and molecular adaptations in skeletal muscle. In this review, we discuss some potentially important redox signalling pathways in skeletal muscle that are involved in acute and chronic responses to contraction and exercise. Specifically, we discuss redox signalling implicated in skeletal muscle contraction force, mitochondrial biogenesis and antioxidant enzyme induction, glucose uptake and muscle hypertrophy. Furthermore, we review evidence investigating the impact of major exogenous antioxidants on these acute and chronic responses to exercise. Redox signalling pathways involved in adaptive responses in skeletal muscle to exercise are not clearly elucidated at present, and further research is required to better define important signalling pathways involved. Evidence of beneficial or detrimental effects of specific antioxidant compounds on exercise adaptations in muscle is similarly limited, particularly in human subjects. Future research is required to not only investigate effects of specific antioxidant compounds on skeletal muscle exercise adaptations, but also to better establish mechanisms of action of specific antioxidants in vivo. Although we feel it remains somewhat premature to make clear recommendations in relation to application of specific antioxidant compounds in different exercise settings, a bulk of evidence suggests that N-acetylcysteine (NAC) is ergogenic through its effects on maintenance of muscle force production during sustained fatiguing events. Nevertheless, a current lack of evidence from studies using performance tests representative of athletic competition and a potential for adverse effects with high doses (>70mg/kg body mass) warrants caution in its use for performance enhancement. In addition, evidence implicates high dose vitamin C (1g/day) and E
Long non-coding RNA-mediated regulation of signaling pathways in gastric cancer.

PubMed

Zong, Wei; Ju, Shaoqing; Jing, Rongrong; Cui, Ming

2018-05-28

Gastric cancer (GC) is one of the most common cancers globally. Because of the high frequency of tumor recurrence, or metastasis, after surgical resection, the prognosis of patients with GC is poor. Therefore, exploring the mechanisms underlying GC is of great importance. Recently, accumulating evidence has begun to show that dysregulated long non-coding RNAs (lncRNAs) participate in the progression of GC via several typical signaling pathways, such as the AKT and MAPK signaling pathways. Moreover, the interactions between lncRNAs and microRNAs appear to represent a novel mechanism in the pathogenesis of GC. This review provides a synopsis of the latest research relating to lncRNAs and associated signaling pathways in GC.
Arachidonic Acid: An Evolutionarily Conserved Signaling Molecule Modulates Plant Stress Signaling Networks[C][W

PubMed Central

Savchenko, Tatyana; Walley, Justin W.; Chehab, E. Wassim; Xiao, Yanmei; Kaspi, Roy; Pye, Matthew F.; Mohamed, Maged E.; Lazarus, Colin M.; Bostock, Richard M.; Dehesh, Katayoon

2010-01-01

Fatty acid structure affects cellular activities through changes in membrane lipid composition and the generation of a diversity of bioactive derivatives. Eicosapolyenoic acids are released into plants upon infection by oomycete pathogens, suggesting they may elicit plant defenses. We exploited transgenic Arabidopsis thaliana plants (designated EP) producing eicosadienoic, eicosatrienoic, and arachidonic acid (AA), aimed at mimicking pathogen release of these compounds. We also examined their effect on biotic stress resistance by challenging EP plants with fungal, oomycete, and bacterial pathogens and an insect pest. EP plants exhibited enhanced resistance to all biotic challenges, except they were more susceptible to bacteria than the wild type. Levels of jasmonic acid (JA) were elevated and levels of salicylic acid (SA) were reduced in EP plants. Altered expression of JA and SA pathway genes in EP plants shows that eicosapolyenoic acids effectively modulate stress-responsive transcriptional networks. Exogenous application of various fatty acids to wild-type and JA-deficient mutants confirmed AA as the signaling molecule. Moreover, AA treatment elicited heightened expression of general stress-responsive genes. Importantly, tomato (Solanum lycopersicum) leaves treated with AA exhibited reduced susceptibility to Botrytis cinerea infection, confirming AA signaling in other plants. These studies support the role of AA, an ancient metazoan signaling molecule, in eliciting plant stress and defense signaling networks. PMID:20935246
Leucine facilitates insulin signaling through a Gαi protein-dependent signaling pathway in hepatocytes.

PubMed

Yang, Xuefeng; Mei, Shuang; Wang, Xiaolei; Li, Xiang; Liu, Rui; Ma, Yan; Hao, Liping; Yao, Ping; Liu, Liegang; Sun, Xiufa; Gu, Haihua; Liu, Zhenqi; Cao, Wenhong

2013-03-29

In this study, we addressed the direct effect of leucine on insulin signaling. In investigating the associated mechanisms, we found that leucine itself does not activate the classical Akt- or ERK1/2 MAP kinase-dependent signaling pathways but can facilitate the insulin-induced phosphorylations of Akt(473) and ERK1/2 in a time- and dose-dependent manner in cultured hepatocytes. The leucine-facilitated insulin-induced phosphorylation of Akt at residue 473 was not affected by knocking down the key component of mTORC1 or -2 complexes but was blocked by inhibition of c-Src (PP2), PI3K (LY294002), Gαi protein (pertussis toxin or siRNA against Gαi1 gene, or β-arrestin 2 (siRNA)). Similarly, the leucine-facilitated insulin activation of ERK1/2 was also blunted by pertussis toxin. We further show that leucine facilitated the insulin-mediated suppression of glucose production and expression of key gluconeogenic genes in a Gαi1 protein-dependent manner in cultured primary hepatocytes. Together, these results show that leucine can directly facilitate insulin signaling through a Gαi protein-dependent intracellular signaling pathway. This is the first evidence showing that macronutrients like amino acid leucine can facilitate insulin signaling through G proteins directly.
Leucine Facilitates Insulin Signaling through a Gαi Protein-dependent Signaling Pathway in Hepatocytes*

PubMed Central

Yang, Xuefeng; Mei, Shuang; Wang, Xiaolei; Li, Xiang; Liu, Rui; Ma, Yan; Hao, Liping; Yao, Ping; Liu, Liegang; Sun, Xiufa; Gu, Haihua; Liu, Zhenqi; Cao, Wenhong

2013-01-01

In this study, we addressed the direct effect of leucine on insulin signaling. In investigating the associated mechanisms, we found that leucine itself does not activate the classical Akt- or ERK1/2 MAP kinase-dependent signaling pathways but can facilitate the insulin-induced phosphorylations of Akt473 and ERK1/2 in a time- and dose-dependent manner in cultured hepatocytes. The leucine-facilitated insulin-induced phosphorylation of Akt at residue 473 was not affected by knocking down the key component of mTORC1 or -2 complexes but was blocked by inhibition of c-Src (PP2), PI3K (LY294002), Gαi protein (pertussis toxin or siRNA against Gαi1 gene, or β-arrestin 2 (siRNA)). Similarly, the leucine-facilitated insulin activation of ERK1/2 was also blunted by pertussis toxin. We further show that leucine facilitated the insulin-mediated suppression of glucose production and expression of key gluconeogenic genes in a Gαi1 protein-dependent manner in cultured primary hepatocytes. Together, these results show that leucine can directly facilitate insulin signaling through a Gαi protein-dependent intracellular signaling pathway. This is the first evidence showing that macronutrients like amino acid leucine can facilitate insulin signaling through G proteins directly. PMID:23404499
Shifting from priming of salicylic acid- to jasmonic acid-regulated defences by Trichoderma protects tomato against the root knot nematode Meloidogyne incognita.

PubMed

Martínez-Medina, Ainhoa; Fernandez, Ivan; Lok, Gerrit B; Pozo, María J; Pieterse, Corné M J; Van Wees, Saskia C M

2017-02-01

Beneficial root endophytes such as Trichoderma spp. can reduce infections by parasitic nematodes through triggering host defences. Little is currently known about the complex hormone signalling underlying the induction of resistance. In this study, we investigated whether Trichoderma modulates the hormone signalling network in the host to induce resistance to nematodes. We investigated the role and the timing of the jasmonic acid (JA)- and salicylic acid (SA)-regulated defensive pathways in Trichoderma-induced resistance to the root knot nematode Meloidogyne incognita. A split-root system of tomato (Solanum lycopersicum) was used to study local and systemic induced defences by analysing nematode performance, defence gene expression, responsiveness to exogenous hormone application, and dependence on SA and JA signalling of Trichoderma-induced resistance. Root colonization by Trichoderma impeded nematode performance both locally and systemically at multiple stages of the parasitism, that is, invasion, galling and reproduction. First, Trichoderma primed SA-regulated defences, which limited nematode root invasion. Then, Trichoderma enhanced JA-regulated defences, thereby antagonizing the deregulation of JA-dependent immunity by the nematodes, which compromised galling and fecundity. Our results show that Trichoderma primes SA- and JA-dependent defences in roots, and that the priming of responsiveness to these hormones upon nematode attack is plastic and adaptive to the parasitism stage. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.
Expanding the view on the evolution of the nematode dauer signalling pathways: refinement through gene gain and pathway co-option.

PubMed

Gilabert, Aude; Curran, David M; Harvey, Simon C; Wasmuth, James D

2016-06-27

Signalling pathways underlie development, behaviour and pathology. To understand patterns in the evolution of signalling pathways, we undertook a comprehensive investigation of the pathways that control the switch between growth and developmentally quiescent dauer in 24 species of nematodes spanning the phylum. Our analysis of 47 genes across these species indicates that the pathways and their interactions are not conserved throughout the Nematoda. For example, the TGF-β pathway was co-opted into dauer control relatively late in a lineage that led to the model species Caenorhabditis elegans. We show molecular adaptations described in C. elegans that are restricted to its genus or even just to the species. Similarly, our analyses both identify species where particular genes have been lost and situations where apparently incorrect orthologues have been identified. Our analysis also highlights the difficulties of working with genome sequences from non-model species as reliance on the published gene models would have significantly restricted our understanding of how signalling pathways evolve. Our approach therefore offers a robust standard operating procedure for genomic comparisons.
Role of CSL-dependent and independent Notch signaling pathways in cell apoptosis.

PubMed

Zeng, Chong; Xing, Rui; Liu, Jing; Xing, Feiyue

2016-01-01

Apoptosis is a normally biological phenomenon in various organisms, involving complexly molecular mechanisms with a series of signaling processes. Notch signaling is found evolutionarily conserved in many species, playing a critical role in embryonic development, normal tissue homeostasis, angiogenesis and immunoregulation. The focus of this review is on currently novel advances about roles of CSL-dependent and independent Notch signaling pathways in cell apoptosis. The CSL can bind Notch intracellular domain (NIC) to act as a switch in mediating transcriptional activation or inactivation of the Notch signaling pathway downstream genes in the nucleus. It shows that CSL-dependent signaling regulates the cell apoptosis through Hes-1-PTEN-AKT-mTOR signaling, but rather the CSL-independent signaling mediates the cell apoptosis possibly via NIC-mTORC2-AKT-mTOR signaling, providing a new insight into apoptotic mechanisms.
The Cell Wall Integrity Signaling Pathway and Its Involvement in Secondary Metabolite Production.

PubMed

Valiante, Vito

2017-12-06

The fungal cell wall is the external and first layer that fungi use to interact with the environment. Every stress signal, before being translated into an appropriate stress response, needs to overtake this layer. Many signaling pathways are involved in translating stress signals, but the cell wall integrity (CWI) signaling pathway is the one responsible for the maintenance and biosynthesis of the fungal cell wall. In fungi, the CWI signal is composed of a mitogen-activated protein kinase (MAPK) module. After the start of the phosphorylation cascade, the CWI signal induces the expression of cell-wall-related genes. However, the function of the CWI signal is not merely the activation of cell wall biosynthesis, but also the regulation of expression and production of specific molecules that are used by fungi to better compete in the environment. These molecules are normally defined as secondary metabolites or natural products. This review is focused on secondary metabolites affected by the CWI signal pathway with a special focus on relevant natural products such as melanins, mycotoxins, and antibacterial compounds.
The non-canonical BMP and Wnt/β-catenin signaling pathways orchestrate early tooth development

PubMed Central

Yuan, Guohua; Yang, Guobin; Zheng, Yuqian; Zhu, Xiaojing; Chen, Zhi; Zhang, Zunyi; Chen, YiPing

2015-01-01

BMP and Wnt signaling pathways play a crucial role in organogenesis, including tooth development. Despite extensive studies, the exact functions, as well as if and how these two pathways act coordinately in regulating early tooth development, remain elusive. In this study, we dissected regulatory functions of BMP and Wnt pathways in early tooth development using a transgenic noggin (Nog) overexpression model (K14Cre;pNog). It exhibits early arrested tooth development, accompanied by reduced cell proliferation and loss of odontogenic fate marker Pitx2 expression in the dental epithelium. We demonstrated that overexpression of Nog disrupted BMP non-canonical activity, which led to a dramatic reduction of cell proliferation rate but did not affect Pitx2 expression. We further identified a novel function of Nog by inhibiting Wnt/β-catenin signaling, causing loss of Pitx2 expression. Co-immunoprecipitation and TOPflash assays revealed direct binding of Nog to Wnts to functionally prevent Wnt/β-catenin signaling. In situ PLA and immunohistochemistry on Nog mutants confirmed in vivo interaction between endogenous Nog and Wnts and modulation of Wnt signaling by Nog in tooth germs. Genetic rescue experiments presented evidence that both BMP and Wnt signaling pathways contribute to cell proliferation regulation in the dental epithelium, with Wnt signaling also controlling the odontogenic fate. Reactivation of both BMP and Wnt signaling pathways, but not of only one of them, rescued tooth developmental defects in K14Cre;pNog mice, in which Wnt signaling can be substituted by transgenic activation of Pitx2. Our results reveal the orchestration of non-canonical BMP and Wnt/β-catenin signaling pathways in the regulation of early tooth development. PMID:25428587
Potential signaling pathways as therapeutic targets for overcoming chemoresistance in mucinous ovarian cancer

PubMed Central

Niiro, Emiko; Morioka, Sachiko; Iwai, Kana; Yamada, Yuki; Ogawa, Kenji; Kawahara, Naoki; Kobayashi, Hiroshi

2018-01-01

Cases of mucinous ovarian cancer are predominantly resistant to chemotherapies. The present review summarizes current knowledge of the therapeutic potential of targeting the Wingless (WNT) pathway, with particular emphasis on preclinical and clinical studies, for improving the chemoresistance and treatment of mucinous ovarian cancer. A review was conducted of English language literature published between January 2000 and October 2017 that concerned potential signaling pathways associated with the chemoresistance of mucinous ovarian cancer. The literature indicated that aberrant activation of growth factor and WNT signaling pathways is specifically observed in mucinous ovarian cancer. An evolutionarily conserved signaling cascade system including epidermal growth factor/RAS/RAF/mitogen-activated protein kinase kinase/extracellular signal-regulated protein kinase, phosphoinositide 3-kinase/Akt and WNT signaling regulates a variety of cellular functions; their crosstalk mutually enhances signaling activity and induces chemoresistance. Novel antagonists, modulators and inhibitors have been developed for targeting the components of the WNT signaling pathway, namely Frizzled, low-density lipoprotein receptor-related protein 5/6, Dishevelled, casein kinase 1, AXIN, glycogen synthase kinase 3β and β-catenin. Targeted inhibition of WNT signaling represents a rational and promising novel approach to overcome chemoresistance, and several WNT inhibitors are being evaluated in preclinical studies. In conclusion, the WNT receptors and their downstream components may serve as novel therapeutic targets for overcoming chemoresistance in mucinous ovarian cancer. PMID:29564122
Preface: cardiac control pathways: signaling and transport phenomena.

PubMed

Sideman, Samuel

2008-03-01

Signaling is part of a complex system of communication that governs basic cellular functions and coordinates cellular activity. Transfer of ions and signaling molecules and their interactions with appropriate receptors, transmembrane transport, and the consequent intracellular interactions and functional cellular response represent a complex system of interwoven phenomena of transport, signaling, conformational changes, chemical activation, and/or genetic expression. The well-being of the cell thus depends on a harmonic orchestration of all these events and the existence of control mechanisms that assure the normal behavior of the various parameters involved and their orderly expression. The ability of cells to sustain life by perceiving and responding correctly to their microenvironment is the basis for development, tissue repair, and immunity, as well as normal tissue homeostasis. Natural deviations, or human-induced interference in the signaling pathways and/or inter- and intracellular transport and information transfer, are responsible for the generation, modulation, and control of diseases. The present overview aims to highlight some major topics of the highly complex cellular information transfer processes and their control mechanisms. Our goal is to contribute to the understanding of the normal and pathophysiological phenomena associated with cardiac functions so that more efficient therapeutic modalities can be developed. Our objective in this volume is to identify and enhance the study of some basic passive and active physical and chemical transport phenomena, physiological signaling pathways, and their biological consequences.
Curcumin and Emodin Down-Regulate TGF-β Signaling Pathway in Human Cervical Cancer Cells

PubMed Central

Thacker, Pooja Chandrakant; Karunagaran, Devarajan

2015-01-01

Cervical cancer is the major cause of cancer related deaths in women, especially in developing countries and Human Papilloma Virus infection in conjunction with multiple deregulated signaling pathways leads to cervical carcinogenesis. TGF-β signaling in later stages of cancer is known to induce epithelial to mesenchymal transition promoting tumor growth. Phytochemicals, curcumin and emodin, are effective as chemopreventive and chemotherapeutic compounds against several cancers including cervical cancer. The main objective of this work was to study the effect of curcumin and emodin on TGF-β signaling pathway and its functional relevance to growth, migration and invasion in two cervical cancer cell lines, SiHa and HeLa. Since TGF-β and Wnt/β-catenin signaling pathways are known to cross talk having common downstream targets, we analyzed the effect of TGF-β on β-catenin (an important player in Wnt/β-catenin signaling) and also studied whether curcumin and emodin modulate them. We observed that curcumin and emodin effectively down regulate TGF-β signaling pathway by decreasing the expression of TGF-β Receptor II, P-Smad3 and Smad4, and also counterbalance the tumorigenic effects of TGF-β by inhibiting the TGF-β-induced migration and invasion. Expression of downstream effectors of TGF-β signaling pathway, cyclinD1, p21 and Pin1, was inhibited along with the down regulation of key mesenchymal markers (Snail and Slug) upon curcumin and emodin treatment. Curcumin and emodin were also found to synergistically inhibit cell population and migration in SiHa and HeLa cells. Moreover, we found that TGF-β activates Wnt/β-catenin signaling pathway in HeLa cells, and curcumin and emodin down regulate the pathway by inhibiting β-catenin. Taken together our data provide a mechanistic basis for the use of curcumin and emodin in the treatment of cervical cancer. PMID:25786122

Curcumin and emodin down-regulate TGF-β signaling pathway in human cervical cancer cells.

PubMed

Thacker, Pooja Chandrakant; Karunagaran, Devarajan

2015-01-01

Cervical cancer is the major cause of cancer related deaths in women, especially in developing countries and Human Papilloma Virus infection in conjunction with multiple deregulated signaling pathways leads to cervical carcinogenesis. TGF-β signaling in later stages of cancer is known to induce epithelial to mesenchymal transition promoting tumor growth. Phytochemicals, curcumin and emodin, are effective as chemopreventive and chemotherapeutic compounds against several cancers including cervical cancer. The main objective of this work was to study the effect of curcumin and emodin on TGF-β signaling pathway and its functional relevance to growth, migration and invasion in two cervical cancer cell lines, SiHa and HeLa. Since TGF-β and Wnt/β-catenin signaling pathways are known to cross talk having common downstream targets, we analyzed the effect of TGF-β on β-catenin (an important player in Wnt/β-catenin signaling) and also studied whether curcumin and emodin modulate them. We observed that curcumin and emodin effectively down regulate TGF-β signaling pathway by decreasing the expression of TGF-β Receptor II, P-Smad3 and Smad4, and also counterbalance the tumorigenic effects of TGF-β by inhibiting the TGF-β-induced migration and invasion. Expression of downstream effectors of TGF-β signaling pathway, cyclinD1, p21 and Pin1, was inhibited along with the down regulation of key mesenchymal markers (Snail and Slug) upon curcumin and emodin treatment. Curcumin and emodin were also found to synergistically inhibit cell population and migration in SiHa and HeLa cells. Moreover, we found that TGF-β activates Wnt/β-catenin signaling pathway in HeLa cells, and curcumin and emodin down regulate the pathway by inhibiting β-catenin. Taken together our data provide a mechanistic basis for the use of curcumin and emodin in the treatment of cervical cancer.
Exercise for the heart: signaling pathways

PubMed Central

Zhang, Haifeng; Xiao, Junjie; Li, Xinli

2015-01-01

Physical exercise, a potent functional intervention in protecting against cardiovascular diseases, is a hot topic in recent years. Exercise has been shown to reduce cardiac risk factors, protect against myocardial damage, and increase cardiac function. This improves quality of life and decreases mortality and morbidity in a variety of cardiovascular diseases, including myocardial infarction, cardiac ischemia/reperfusion injury, diabetic cardiomyopathy, cardiac aging, and pulmonary hypertension. The cellular adaptation to exercise can be associated with both endogenous and exogenous factors: 1) exercise induces cardiac growth via hypertrophy and renewal of cardiomyocytes, and 2) exercise induces endothelial progenitor cells to proliferate, migrate and differentiate into mature endothelial cells, giving rise to endothelial regeneration and angiogenesis. The cellular adaptations associated with exercise are due to the activation of several signaling pathways, in particular, the growth factor neuregulin1 (NRG1)-ErbB4-C/EBPβ and insulin-like growth factor (IGF)-1-PI3k-Akt signaling pathways. Of interest, microRNAs (miRNAs, miRs) such as miR-222 also play a major role in the beneficial effects of exercise. Thus, exploring the mechanisms mediating exercise-induced benefits will be instrumental for devising new effective therapies against cardiovascular diseases. PMID:26318584
Chemical modulation of glycerolipid signaling and metabolic pathways

PubMed Central

Scott, Sarah A.; Mathews, Thomas P.; Ivanova, Pavlina T.; Lindsley, Craig W.; Brown, H. Alex

2014-01-01

Thirty years ago, glycerolipids captured the attention of biochemical researchers as novel cellular signaling entities. We now recognize that these biomolecules occupy signaling nodes critical to a number of physiological and pathological processes. Thus, glycerolipid-metabolizing enzymes present attractive targets for new therapies. A number of fields—ranging from neuroscience and cancer to diabetes and obesity—have elucidated the signaling properties of glycerolipids. The biochemical literature teems with newly emerging small molecule inhibitors capable of manipulating glycerolipid metabolism and signaling. This ever-expanding pool of chemical modulators appears daunting to those interested in exploiting glycerolipid-signaling pathways in their model system of choice. This review distills the current body of literature surrounding glycerolipid metabolism into a more approachable format, facilitating the application of small molecule inhibitors to novel systems. PMID:24440821
Insulin-like growth factor-1 suppresses the Myostatin signaling pathway during myogenic differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Retamales, A.; Zuloaga, R.; Valenzuela, C.A.

Myogenic differentiation is a complex and well-coordinated process for generating mature skeletal muscle fibers. This event is autocrine/paracrine regulated by growth factors, principally Myostatin (MSTN) and Insulin-like Growth Factor-1 (IGF-1). Myostatin, a member of the transforming growth factor-β superfamily, is a negative regulator of skeletal muscle growth in vertebrates that exerts its inhibitory function by activating Smad transcription factors. In contrast, IGF-1 promotes the differentiation of skeletal myoblasts by activating the PI3K/Akt signaling pathway. This study reports on a novel functional crosstalk between the IGF-1 and MSTN signaling pathways, as mediated through interaction between PI3K/Akt and Smad3. Stimulation of skeletalmore » myoblasts with MSTN resulted in a transient increase in the pSmad3:Smad3 ratio and Smad-dependent transcription. Moreover, MSTN inhibited myod gene expression and myoblast fusion in an Activin receptor-like kinase/Smad3-dependent manner. Preincubation of skeletal myoblasts with IGF-1 blocked MSTN-induced Smad3 activation, promoting myod expression and myoblast differentiation. This inhibitory effect of IGF-1 on the MSTN signaling pathway was dependent on IGF-1 receptor, PI3K, and Akt activities. Finally, immunoprecipitation assay analysis determined that IGF-1 pretreatment increased Akt and Smad3 interaction. These results demonstrate that the IGF-1/PI3K/Akt pathway may inhibit MSTN signaling during myoblast differentiation, providing new insight to existing knowledge on the complex crosstalk between both growth factors. - Highlights: • IGF-1 inhibits Myostatin canonical signaling pathway through IGF-1R/PI3K/Akt pathway. • IGF-1 promotes myoblast differentiation through a direct blocking of Myostatin signaling pathway. • IGF-1 induces the interaction of Akt with Smad3 in skeletal myoblast.« less
Activation of the yeast Hippo pathway by phosphorylation-dependent assembly of signaling complexes.

PubMed

Rock, Jeremy M; Lim, Daniel; Stach, Lasse; Ogrodowicz, Roksana W; Keck, Jamie M; Jones, Michele H; Wong, Catherine C L; Yates, John R; Winey, Mark; Smerdon, Stephen J; Yaffe, Michael B; Amon, Angelika

2013-05-17

Scaffold-assisted signaling cascades guide cellular decision-making. In budding yeast, one such signal transduction pathway called the mitotic exit network (MEN) governs the transition from mitosis to the G1 phase of the cell cycle. The MEN is conserved and in metazoans is known as the Hippo tumor-suppressor pathway. We found that signaling through the MEN kinase cascade was mediated by an unusual two-step process. The MEN kinase Cdc15 first phosphorylated the scaffold Nud1. This created a phospho-docking site on Nud1, to which the effector kinase complex Dbf2-Mob1 bound through a phosphoserine-threonine binding domain, in order to be activated by Cdc15. This mechanism of pathway activation has implications for signal transmission through other kinase cascades and might represent a general principle in scaffold-assisted signaling.
A Role for the GCC-Box in Jasmonate-Mediated Activation of the PDF1.2 Gene of Arabidopsis1

PubMed Central

Brown, Rebecca L.; Kazan, Kemal; McGrath, Ken C.; Maclean, Don J.; Manners, John M.

2003-01-01

The PDF1.2 gene of Arabidopsis encoding a plant defensin is commonly used as a marker for characterization of the jasmonate-dependent defense responses. Here, using PDF1.2 promoter-deletion lines linked to the β-glucoronidase-reporter gene, we examined putative promoter elements associated with jasmonate-responsive expression of this gene. Using stably transformed plants, we first characterized the extended promoter region that positively regulates basal expression from the PDF1.2 promoter. Second, using promoter deletion constructs including one from which the GCC-box region was deleted, we observed a substantially lower response to jasmonate than lines carrying this motif. In addition, point mutations introduced into the core GCC-box sequence substantially reduced jasmonate responsiveness, whereas addition of a 20-nucleotide-long promoter element carrying the core GCC-box and flanking nucleotides provided jasmonate responsiveness to a 35S minimal promoter. Taken together, these results indicated that the GCC-box plays a key role in conferring jasmonate responsiveness to the PDF1.2 promoter. However, deletion or specific mutations introduced into the core GCC-box did not completely abolish the jasmonate responsiveness of the promoter, suggesting that the other promoter elements lying downstream from the GCC-box region may also contribute to jasmonate responsiveness. In other experiments, we identified a jasmonate- and pathogen-responsive ethylene response factor transcription factor, AtERF2, which when overexpressed in transgenic Arabidopsis plants activated transcription from the PDF1.2, Thi2.1, and PR4 (basic chitinase) genes, all of which contain a GCC-box sequence in their promoters. Our results suggest that in addition to their roles in regulating ethylene-mediated gene expression, ethylene response factors also appear to play important roles in regulating jasmonate-responsive gene expression, possibly via interaction with the GCC-box. PMID:12805630
Three branches of phospholipase C signaling pathway promote hepatocyte growth in rat liver regeneration.

PubMed

Xu, G G; Geng, Z; Zhou, X C; He, Y G; He, T T; Mei, J X; Yang, Y J; Liu, Y Q; Xu, C S

2015-05-29

In general, the phospholipase C (PLC) signaling pathway is involved in many physiological activities, including cell growth. However, little is known regarding how the PLC signaling pathway participates in regulating hepatocyte (HC) growth during liver regeneration (LR). To further explore the influence of the PLC signaling pathway on HCs at the cellular level, HCs of high purity and vitality were isolated using Percoll density-gradient centrifugation after partial hepatectomy. The genes of the PLC signaling pathway and target genes of transcription factors in the pathway were obtained by searching the pathways and transcription factor databases, and changes in gene expression of isolated HCs were examined using the Rat Genome 230 2.0 Microarray. The results suggested that various genes involved in the pathway (including 151 known genes and 39 homologous genes) and cell growth (including 262 known genes and 37 homologous genes) were associated with LR. Subsequently, the synergetic effect of these genes in LR was analyzed using a mathematical model (Et) according to their expression profiles. The results showed that the Et values of G protein-coupled receptor/PLC, integrin/PLC, and growth factor receptor/PLC branches of the PLC pathway were all significantly strengthened during the progression and termination phases of LR. The synergetic effect of target genes, in parallel with target gene-related cell growth, was also enhanced during whole rat LR, suggesting the potential positive effect of PLC on HC growth. The present data indicate that the PLC signaling pathway may promote HC growth through 3 mechanisms during rat LR after partial hepatectomy.
Hijacking common mycorrhizal networks for herbivore-induced defence signal transfer between tomato plants

PubMed Central

Song, Yuan Yuan; Ye, Mao; Li, Chuanyou; He, Xinhua; Zhu-Salzman, Keyan; Wang, Rui Long; Su, Yi Juan; Luo, Shi Ming; Zeng, Ren Sen

2014-01-01

Common mycorrhizal networks (CMNs) link multiple plants together. We hypothesized that CMNs can serve as an underground conduit for transferring herbivore-induced defence signals. We established CMN between two tomato plants in pots with mycorrhizal fungus Funneliformis mosseae, challenged a ‘donor' plant with caterpillar Spodoptera litura, and investigated defence responses and insect resistance in neighbouring CMN-connected ‘receiver' plants. After CMN establishment caterpillar infestation on ‘donor' plant led to increased insect resistance and activities of putative defensive enzymes, induction of defence-related genes and activation of jasmonate (JA) pathway in the ‘receiver' plant. However, use of a JA biosynthesis defective mutant spr2 as ‘donor' plants resulted in no induction of defence responses and no change in insect resistance in ‘receiver' plants, suggesting that JA signalling is required for CMN-mediated interplant communication. These results indicate that plants are able to hijack CMNs for herbivore-induced defence signal transfer and interplant defence communication. PMID:24468912
SignaLink 2 – a signaling pathway resource with multi-layered regulatory networks

PubMed Central

2013-01-01

Background Signaling networks in eukaryotes are made up of upstream and downstream subnetworks. The upstream subnetwork contains the intertwined network of signaling pathways, while the downstream regulatory part contains transcription factors and their binding sites on the DNA as well as microRNAs and their mRNA targets. Currently, most signaling and regulatory databases contain only a subsection of this network, making comprehensive analyses highly time-consuming and dependent on specific data handling expertise. The need for detailed mapping of signaling systems is also supported by the fact that several drug development failures were caused by undiscovered cross-talk or regulatory effects of drug targets. We previously created a uniformly curated signaling pathway resource, SignaLink, to facilitate the analysis of pathway cross-talks. Here, we present SignaLink 2, which significantly extends the coverage and applications of its predecessor. Description We developed a novel concept to integrate and utilize different subsections (i.e., layers) of the signaling network. The multi-layered (onion-like) database structure is made up of signaling pathways, their pathway regulators (e.g., scaffold and endocytotic proteins) and modifier enzymes (e.g., phosphatases, ubiquitin ligases), as well as transcriptional and post-transcriptional regulators of all of these components. The user-friendly website allows the interactive exploration of how each signaling protein is regulated. The customizable download page enables the analysis of any user-specified part of the signaling network. Compared to other signaling resources, distinctive features of SignaLink 2 are the following: 1) it involves experimental data not only from humans but from two invertebrate model organisms, C. elegans and D. melanogaster; 2) combines manual curation with large-scale datasets; 3) provides confidence scores for each interaction; 4) operates a customizable download page with multiple file formats
Characteristic Markers of the WNT Signaling Pathways Are Differentially Expressed in Osteoarthritic Cartilage

PubMed Central

Dehne, T.; Lindahl, A.; Brittberg, M.; Pruss, A.; Ringe, J.; Sittinger, M.; Karlsson, C.

2012-01-01

Objective: It is well known that expression of markers for WNT signaling is dysregulated in osteoarthritic (OA) bone. However, it is still not fully known if the expression of these markers also is affected in OA cartilage. The aim of this study was therefore to examine this issue. Methods: Human cartilage biopsies from OA and control donors were subjected to genome-wide oligonucleotide microarrays. Genes involved in WNT signaling were selected using the BioRetis database, KEGG pathway analysis was searched using DAVID software tools, and cluster analysis was performed using Genesis software. Results from the microarray analysis were verified using quantitative real-time PCR and immunohistochemistry. In order to study the impact of cytokines for the dysregulated WNT signaling, OA and control chondrocytes were stimulated with interleukin-1 and analyzed with real-time PCR for their expression of WNT-related genes. Results: Several WNT markers displayed a significantly altered expression in OA compared to normal cartilage. Interestingly, inhibitors of the canonical and planar cell polarity WNT signaling pathways displayed significantly increased expression in OA cartilage, while the Ca2+/WNT signaling pathway was activated. Both real-time PCR and immunohistochemistry verified the microarray results. Real-time PCR analysis demonstrated that interleukin-1 upregulated expression of important WNT markers. Conclusions: WNT signaling is significantly affected in OA cartilage. The result suggests that both the canonical and planar cell polarity WNT signaling pathways were partly inhibited while the Ca2+/WNT pathway was activated in OA cartilage. PMID:26069618
ROS signaling pathways and biological rhythms: perspectives in crustaceans.

PubMed

Fanjul-Moles, Maria Luisa

2013-01-01

This work reviews concepts regarding the endogenous circadian clock and the relationship between oxidative stress (OS), light and entrainment in different organisms including crustaceans, particularly crayfish. In the first section, the molecular control of circadian rhythms in invertebrates, particularly in Drosophila, is reviewed, and this model is contrasted with recent reports on the circadian genes and proteins in crayfish. Second, the redox mechanisms and signaling pathways that participate in the entrainment of the circadian clock in different organisms are reviewed. Finally, the light signals and transduction pathways involved in the entrainment of the circadian clock, specifically in relation to cryptochromes (CRYs) and their dual role in the circadian clock of different animal groups and their possible relationship to the circadian clock and redox mechanisms in crustaceans is discussed. The relationship between metabolism, ROS signals and transcription factors, such as HIF-1 alpha in crayfish, as well as the possibility that HIF-1 alpha participates in the regulation of circadian control genes (ccgs) in crustaceans is discussed.
[Review for treatment effect and signaling pathway regulation of kidney-tonifying traditional Chinese medicine on osteoporosis].

PubMed

Xiao, Ya-Ping; Zeng, Jie; Jiao, Lin-Na; Xu, Xiao-Yu

2018-01-01

The treatment effect and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied, but there is no systematic summary currently. This review comprehensively collected and analyzed the traditional Chinese medicines on the treatment and signaling pathway regulation of osteoporosis in recent ten years, such as Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix. Based on the existing findings, the following conclusions were obtained: ①kidney-tonifying traditional Chinese medicine treated osteoporosis mainly through BMP-Smads, Wnt/ β -catenin, MAPK, PI3K/AKT signaling pathway to promote osteoblast bone formation and through OPG/RANKL/ RANK, estrogen, CTSK signaling pathway to inhibit osteoclasts of bone resorption. Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus and Psoraleae Fructus up-regulated the expression of key proteins and genes of BMP-Smads and Wnt/ β -catenin signaling pathways to promote bone formation. Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix inhibited the bone resorption by mediating the OPG/RANKL/RANK signaling pathway. ②Kidney-tonifying traditional Chinese medicine prevented and treated osteoporosis through a variety of ways: icariin in Epimedii Folium, naringin in Drynariae Rhizoma, osthole in Cnidii Fructus and psoralen in Psoraleae Fructus can regulate BMP-Smads, Wnt/ β -catenin signaling pathway to promote bone formation, but also activate OPG/RANKL/RANK, CTSK and other signaling pathways to inhibit bone resorption. ③The crosstalk of the signaling pathways and the animal experiments of the traditional Chinese medicine on the prevention and treatment of osteoporosis as well as their multi-target mechanism and comprehensive regulation need further clarification. Copyright© by the Chinese Pharmaceutical Association.
SMAD4 feedback regulates the canonical TGF-β signaling pathway to control granulosa cell apoptosis.

PubMed

Du, Xing; Pan, Zengxiang; Li, Qiqi; Liu, Honglin; Li, Qifa

2018-02-02

Canonical TGF-β signals are transduced from the cell surface to the cytoplasm, and then translocated into the nucleus, a process that involves ligands (TGF-β1), receptors (TGFBR2/1), receptor-activated SMADs (SMAD2/3), and the common SMAD (SMAD4). Here we provide evidence that SMAD4, a core component of the canonical TGF-β signaling pathway, regulates the canonical TGF-β signaling pathway in porcine granulosa cells (GCs) through a feedback mechanism. Genome-wide analysis and qRT-PCR revealed that SMAD4 affected miRNA biogenesis in GCs. Interestingly, TGFBR2, the type II receptor of the canonical TGF-β signaling pathway, was downregulated in SMAD4-silenced GCs and found to be a common target of SMAD4-inhibited miRNAs. miR-425, the most significantly elevated miRNA in SMAD4-silenced GCs, mediated the SMAD4 feedback regulation of the TGF-β signaling pathway. This was accomplished through a direct interaction between the transcription factor SMAD4 and the miR-425 promoter, and a direct interaction between miR-425 and the TGFBR2 3'-UTR. Furthermore, miR-425 enhanced GC apoptosis by targeting TGFBR2 and the canonical TGF-β signaling pathway, which was rescued by SMAD4 and TGF-β1. Overall, our findings demonstrate that a positive feedback mechanism exists within the canonical TGF-β signaling pathway. This study also provides new insights into mechanism underlying the canonical TGF-β signaling pathway, which regulates GC function and follicular development.
Jasmonic acid-induced volatiles of Brassica oleracea attract parasitoids: effects of time and dose, and comparison with induction by herbivores

PubMed Central

Bruinsma, Maaike; Posthumus, Maarten A.; Mumm, Roland; Mueller, Martin J.; van Loon, Joop J. A.; Dicke, Marcel

2009-01-01

Caterpillar feeding induces direct and indirect defences in brassicaceous plants. This study focused on the role of the octadecanoid pathway in induced indirect defence in Brassica oleracea. The effect of induction by exogenous application of jasmonic acid (JA) on the responses of Brussels sprouts plants and on host-location behaviour of associated parasitoid wasps was studied. Feeding by the biting–chewing herbivores Pieris rapae and Plutella xylostella resulted in significantly increased endogenous levels of JA, a central component in the octadecanoid signalling pathway that mediates induced plant defence. The levels of the intermediate 12-oxophyto-dienoic acid (OPDA) were significantly induced only after P. rapae feeding. Three species of parasitoid wasps, Cotesia glomerata, C. rubecula, and Diadegma semiclausum, differing in host range and host specificity, were tested for their behavioural responses to volatiles from herbivore-induced, JA-induced, and non-induced plants. All three species were attracted to volatiles from JA-induced plants compared with control plants; however, they preferred volatiles from herbivore-induced plants over volatiles from JA-induced plants. Attraction of C. glomerata depended on both timing and dose of JA application. JA-induced plants produced larger quantities of volatiles than herbivore-induced and control plants, indicating that not only quantity, but also quality of the volatile blend is important in the host-location behaviour of the wasps. PMID:19451186
Intrinsic noise analysis and stochastic simulation on transforming growth factor beta signal pathway

NASA Astrophysics Data System (ADS)

Wang, Lu; Ouyang, Qi

2010-10-01

A typical biological cell lives in a small volume at room temperature; the noise effect on the cell signal transduction pathway may play an important role in its dynamics. Here, using the transforming growth factor-β signal transduction pathway as an example, we report our stochastic simulations of the dynamics of the pathway and introduce a linear noise approximation method to calculate the transient intrinsic noise of pathway components. We compare the numerical solutions of the linear noise approximation with the statistic results of chemical Langevin equations, and find that they are quantitatively in agreement with the other. When transforming growth factor-β dose decreases to a low level, the time evolution of noise fluctuation of nuclear Smad2—Smad4 complex indicates the abnormal enhancement in the transient signal activation process.
Impact of salicylic acid- and jasmonic acid-regulated defences on root colonization by Trichoderma harzianum T-78.

PubMed

Martínez-Medina, Ainhoa; Appels, Freek V W; van Wees, Saskia C M

2017-08-03

We recently found that the beneficial fungus Trichoderma harzianum T-78 primes tomato plants for salicylic acid (SA)- and jasmonic acid (JA)-regulated defenses, resulting in enhanced resistance against the root knot nematode Meloidogyne incognita. By using SA- and JA-impaired mutant lines and exogenous hormonal application, here we investigated whether the SA- and JA-pathways also have a role in T-78 root colonization of Arabidopsis thaliana. Endophytic colonization by T-78 was faster in the SA-impaired mutant sid2 than in the wild type. Moreover, elicitation of SA-dependent defenses by SA application reduced T-78 colonization, indicating that the SA-pathway affects T-78 endophytism. In contrast, elicitation of the JA-pathway, which antagonized SA-dependent defenses, resulted in enhanced endophytic colonization by T-78. These findings are in line with our previous observation that SA-dependent defenses are repressed by T-78, which likely aids colonization by the endophytic fungus.
Expression of geminiviral AC2 RNA silencing suppressor changes sugar and jasmonate responsive gene expression in transgenic tobacco plants

PubMed Central

2012-01-01

Background RNA-silencing is a conserved gene regulation and surveillance machinery, which in plants, is also used as major defence mechanism against viruses. Various virus-specific dsRNA structures are recognized by the silencing machinery leading to degradation of the viral RNAs or, as in case of begomoviruses, to methylation of their DNA genomes. Viruses produce specific RNA silencing suppressor (RSS) proteins to prevent these host defence mechanisms, and as these interfere with the silencing machinery they also disturb the endogenous silencing reactions. In this paper, we describe how expression of AC2 RSS, derived from African cassava mosaic geminivirus changes transcription profile in tobacco (Nicotiana tabacum) leaves and in flowers. Results Expression of AC2 RSS in transgenic tobacco plants induced clear phenotypic changes both in leaves and in flowers. Transcriptomes of these plants were strongly altered, with total of 1118 and 251 differentially expressed genes in leaves and flowers, respectively. The three most up-regulated transcript groups were related to stress, cell wall modifications and signalling, whereas the three most down-regulated groups were related to translation, photosynthesis and transcription. It appears that many of the gene expression alterations appeared to be related to enhanced biosynthesis of jasmonate and ethylene, and consequent enhancement of the genes and pathways that are regulated by these hormones, or to the retrograde signalling caused by the reduced photosynthetic activity and sugar metabolism. Comparison of these results to a previous transcriptional profiling of HC-Pro RSS-expressing plants revealed that some of same genes were induced by both RSSs, but their expression levels were typically higher in AC2 than in HC-Pro RSS expressing plants. All in all, a large number of transcript alterations were found to be specific to each of the RSS expressing transgenic plants. Conclusions AC2 RSS in transgenic tobacco plants
Ontology based standardization of Petri net modeling for signaling pathways.

PubMed

Takai-Igarashi, Takako

2005-01-01

Taking account of the great availability of Petri nets in modeling and analyzing large complicated signaling networks, semantics of Petri nets is in need of systematization for the purpose of consistency and reusability of the models. This paper reports on standardization of units of Petri nets on the basis of an ontology that gives an intrinsic definition to the process of signaling in signaling pathways.
Ontology based standardization of petri net modeling for signaling pathways.

PubMed

Takai-Igarashi, Takako

2011-01-01

Taking account of the great availability of Petri nets in modeling and analyzing large complicated signaling networks, semantics of Petri nets is in need of systematization for the purpose of consistency and reusability of the models. This paper reports on standardization of units of Petri nets on the basis of an ontology that gives an intrinsic definition to the process of signaling in signaling pathways.
Dynamics and control of the ERK signaling pathway: Sensitivity, bistability, and oscillations.

PubMed

Arkun, Yaman; Yasemi, Mohammadreza

2018-01-01

Cell signaling is the process by which extracellular information is transmitted into the cell to perform useful biological functions. The ERK (extracellular-signal-regulated kinase) signaling controls several cellular processes such as cell growth, proliferation, differentiation and apoptosis. The ERK signaling pathway considered in this work starts with an extracellular stimulus and ends with activated (double phosphorylated) ERK which gets translocated into the nucleus. We model and analyze this complex pathway by decomposing it into three functional subsystems. The first subsystem spans the initial part of the pathway from the extracellular growth factor to the formation of the SOS complex, ShC-Grb2-SOS. The second subsystem includes the activation of Ras which is mediated by the SOS complex. This is followed by the MAPK subsystem (or the Raf-MEK-ERK pathway) which produces the double phosphorylated ERK upon being activated by Ras. Although separate models exist in the literature at the subsystems level, a comprehensive model for the complete system including the important regulatory feedback loops is missing. Our dynamic model combines the existing subsystem models and studies their steady-state and dynamic interactions under feedback. We establish conditions under which bistability and oscillations exist for this important pathway. In particular, we show how the negative and positive feedback loops affect the dynamic characteristics that determine the cellular outcome.

Regulation of Cell Wall Biogenesis in Saccharomyces cerevisiae: The Cell Wall Integrity Signaling Pathway

PubMed Central

Levin, David E.

2011-01-01

The yeast cell wall is a strong, but elastic, structure that is essential not only for the maintenance of cell shape and integrity, but also for progression through the cell cycle. During growth and morphogenesis, and in response to environmental challenges, the cell wall is remodeled in a highly regulated and polarized manner, a process that is principally under the control of the cell wall integrity (CWI) signaling pathway. This pathway transmits wall stress signals from the cell surface to the Rho1 GTPase, which mobilizes a physiologic response through a variety of effectors. Activation of CWI signaling regulates the production of various carbohydrate polymers of the cell wall, as well as their polarized delivery to the site of cell wall remodeling. This review article centers on CWI signaling in Saccharomyces cerevisiae through the cell cycle and in response to cell wall stress. The interface of this signaling pathway with other pathways that contribute to the maintenance of cell wall integrity is also discussed. PMID:22174182
Methyl jasmonate elicits the biotransformation of geraniol stored as its glucose conjugate into methyl geranate in Achyranthes bidentata plant.

PubMed

Tamogami, Shigeru; Agrawal, Ganesh K; Rakwal, Randeep

2016-12-01

To investigate the biotransformation pathway of airborne geraniol by Achyranthes bidentata (A. bidentata), deuterium labeled geraniol was applied with or without methyl jasmonate (MeJA), and the biosynthesized metabolites were analyzed. In A. bidentata leaves, geraniol was conjugated with glucose. The conjugate was then metabolized to afford methyl geranate only under MeJA elicitation. MeJA elicits the biotransformation of geraniol into methyl geranate by inducing the conversion of the intermediate, glucose conjugate of geraniol. Copyright Â© 2016 Elsevier Masson SAS. All rights reserved.
Emerging role of Hippo signalling pathway in bladder cancer.

PubMed

Xia, Jianling; Zeng, Ming; Zhu, Hua; Chen, Xiangjian; Weng, Zhiliang; Li, Shi

2018-01-01

Bladder cancer (BC) is one of the most common cancers worldwide with a high progression rate and poor prognosis. The Hippo signalling pathway is a conserved pathway that plays a crucial role in cellular proliferation, differentiation and apoptosis. Furthermore, dysregulation and/or malfunction of the Hippo pathway is common in various human tumours, including BC. In this review, an overview of the Hippo pathway in BC and other cancers is presented. We focus on recent data regarding the Hippo pathway, its network and the regulation of the downstream co-effectors YAP1/TAZ. The core components of the Hippo pathway, which induce BC stemness acquisition, metastasis and chemoresistance, will be emphasized. Additional research on the Hippo pathway will advance our understanding of the mechanism of BC as well as the development and progression of other cancers and may be exploited therapeutically. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
DOE Office of Scientific and Technical Information (OSTI.GOV)

Taki-Nakano, Nozomi; Advanced Drug Research Laboratories, Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda, Saitama 335-8505; Kotera, Jun

Jasmonates are plant lipid–derived oxylipins that act as key signaling compounds in plant immunity, germination, and development. Although some physiological activities of natural jasmonates in mammalian cells have been investigated, their anti-inflammatory actions in mammalian cells remain unclear. Here, we investigated whether jasmonates protect mouse microglial MG5 cells against lipopolysaccharide (LPS)–induced inflammation. Among the jasmonates tested, only 12-oxo-phytodienoic acid (OPDA) suppressed LPS-induced expression of the typical inflammatory cytokines interleukin-6 and tumor necrosis factor α. In addition, only OPDA reduced LPS-induced nitric oxide production through a decrease in the level of inducible nitric oxide synthase. Further mechanistic studies showed that OPDAmore » suppressed neuroinflammation by inhibiting nuclear factor κB and p38 mitogen-activated protein kinase signaling in LPS-activated MG5 cells. In addition, OPDA induced expression of suppressor of cytokine signaling-1 (SOCS-1), a negative regulator of inflammation, in MG5 cells. Finally, we found that the nuclear factor erythroid 2-related factor 2 signaling cascade induced by OPDA is not involved in the anti-inflammatory effects of OPDA. These results demonstrate that OPDA inhibited LPS-induced cell inflammation in mouse microglial cells via multiple pathways, including suppression of nuclear factor κB, inhibition of p38, and activation of SOCS-1 signaling. -- Highlights: •OPDA attenuates LPS-induced inflammatory cytokines such as IL-6 and TNF-α. •OPDA reduces LPS-induced iNOS expression and NO production. •OPDA suppresses NF-κB and p38 pathways and activates SOCS-1 signaling.« less
Deciphering Signaling Pathway Networks to Understand the Molecular Mechanisms of Metformin Action

PubMed Central

Sun, Jingchun; Zhao, Min; Jia, Peilin; Wang, Lily; Wu, Yonghui; Iverson, Carissa; Zhou, Yubo; Bowton, Erica; Roden, Dan M.; Denny, Joshua C.; Aldrich, Melinda C.; Xu, Hua; Zhao, Zhongming

2015-01-01

A drug exerts its effects typically through a signal transduction cascade, which is non-linear and involves intertwined networks of multiple signaling pathways. Construction of such a signaling pathway network (SPNetwork) can enable identification of novel drug targets and deep understanding of drug action. However, it is challenging to synopsize critical components of these interwoven pathways into one network. To tackle this issue, we developed a novel computational framework, the Drug-specific Signaling Pathway Network (DSPathNet). The DSPathNet amalgamates the prior drug knowledge and drug-induced gene expression via random walk algorithms. Using the drug metformin, we illustrated this framework and obtained one metformin-specific SPNetwork containing 477 nodes and 1,366 edges. To evaluate this network, we performed the gene set enrichment analysis using the disease genes of type 2 diabetes (T2D) and cancer, one T2D genome-wide association study (GWAS) dataset, three cancer GWAS datasets, and one GWAS dataset of cancer patients with T2D on metformin. The results showed that the metformin network was significantly enriched with disease genes for both T2D and cancer, and that the network also included genes that may be associated with metformin-associated cancer survival. Furthermore, from the metformin SPNetwork and common genes to T2D and cancer, we generated a subnetwork to highlight the molecule crosstalk between T2D and cancer. The follow-up network analyses and literature mining revealed that seven genes (CDKN1A, ESR1, MAX, MYC, PPARGC1A, SP1, and STK11) and one novel MYC-centered pathway with CDKN1A, SP1, and STK11 might play important roles in metformin’s antidiabetic and anticancer effects. Some results are supported by previous studies. In summary, our study 1) develops a novel framework to construct drug-specific signal transduction networks; 2) provides insights into the molecular mode of metformin; 3) serves a model for exploring signaling pathways
Cellular Metabolic and Autophagic Pathways: Traffic Control by Redox Signaling

PubMed Central

Dodson, Matthew; Darley-Usmar, Victor; Zhang, Jianhua

2013-01-01

It has been established that the key metabolic pathways of glycolysis and oxidative phosphorylation are intimately related to redox biology through control of cell signaling. Under physiological conditions glucose metabolism is linked to control of the NADH/NAD redox couple, as well as providing the major reductant, NADPH, for thiol-dependent antioxidant defenses. Retrograde signaling from the mitochondrion to the nucleus or cytosol controls cell growth and differentiation. Under pathological conditions mitochondria are targets for reactive oxygen and nitrogen species and are critical in controlling apoptotic cell death. At the interface of these metabolic pathways, the autophagy-lysosomal pathway functions to maintain mitochondrial quality, and generally serves an important cytoprotective function. In this review we will discuss the autophagic response to reactive oxygen and nitrogen species that are generated from perturbations of cellular glucose metabolism and bioenergetic function. PMID:23702245
Drosophila Nociceptive Sensitization Requires BMP Signaling via the Canonical SMAD Pathway

PubMed Central

Follansbee, Taylor L.; Gjelsvik, Kayla J.; Brann, Courtney L.; McParland, Aidan L.

2017-01-01

Nociceptive sensitization is a common feature in chronic pain, but its basic cellular mechanisms are only partially understood. The present study used the Drosophila melanogaster model system and a candidate gene approach to identify novel components required for modulation of an injury-induced nociceptive sensitization pathway presumably downstream of Hedgehog. This study demonstrates that RNAi silencing of a member of the Bone Morphogenetic Protein (BMP) signaling pathway, Decapentaplegic (Dpp), specifically in the Class IV multidendritic nociceptive neuron, significantly attenuated ultraviolet injury-induced sensitization. Furthermore, overexpression of Dpp in Class IV neurons was sufficient to induce thermal hypersensitivity in the absence of injury. The requirement of various BMP receptors and members of the SMAD signal transduction pathway in nociceptive sensitization was also demonstrated. The effects of BMP signaling were shown to be largely specific to the sensitization pathway and not associated with changes in nociception in the absence of injury or with changes in dendritic morphology. Thus, the results demonstrate that Dpp and its pathway play a crucial and novel role in nociceptive sensitization. Because the BMP family is so strongly conserved between vertebrates and invertebrates, it seems likely that the components analyzed in this study represent potential therapeutic targets for the treatment of chronic pain in humans. SIGNIFICANCE STATEMENT This report provides a genetic analysis of primary nociceptive neuron mechanisms that promote sensitization in response to injury. Drosophila melanogaster larvae whose primary nociceptive neurons were reduced in levels of specific components of the BMP signaling pathway, were injured and then tested for nocifensive responses to a normally subnoxious stimulus. Results suggest that nociceptive neurons use the BMP2/4 ligand, along with identified receptors and intracellular transducers to transition to a
Deciphering the hormonal signalling network behind the systemic resistance induced by Trichoderma harzianum in tomato

PubMed Central

Martínez-Medina, Ainhoa; Fernández, Iván; Sánchez-Guzmán, María J.; Jung, Sabine C.; Pascual, Jose A.; Pozo, María J.

2013-01-01

Root colonization by selected Trichoderma isolates can activate in the plant a systemic defense response that is effective against a broad-spectrum of plant pathogens. Diverse plant hormones play pivotal roles in the regulation of the defense signaling network that leads to the induction of systemic resistance triggered by beneficial organisms [induced systemic resistance (ISR)]. Among them, jasmonic acid (JA) and ethylene (ET) signaling pathways are generally essential for ISR. However, Trichoderma ISR (TISR) is believed to involve a wider variety of signaling routes, interconnected in a complex network of cross-communicating hormone pathways. Using tomato as a model, an integrative analysis of the main mechanisms involved in the systemic resistance induced by Trichoderma harzianum against the necrotrophic leaf pathogen Botrytis cinerea was performed. Root colonization by T. harzianum rendered the leaves more resistant to B. cinerea independently of major effects on plant nutrition. The analysis of disease development in shoots of tomato mutant lines impaired in the synthesis of the key defense-related hormones JA, ET, salicylic acid (SA), and abscisic acid (ABA), and the peptide prosystemin (PS) evidenced the requirement of intact JA, SA, and ABA signaling pathways for a functional TISR. Expression analysis of several hormone-related marker genes point to the role of priming for enhanced JA-dependent defense responses upon pathogen infection. Together, our results indicate that although TISR induced in tomato against necrotrophs is mainly based on boosted JA-dependent responses, the pathways regulated by the plant hormones SA- and ABA are also required for successful TISR development. PMID:23805146
Bipolar cell gap junctions serve major signaling pathways in the human retina.

PubMed

Kántor, Orsolya; Varga, Alexandra; Nitschke, Roland; Naumann, Angela; Énzsöly, Anna; Lukáts, Ákos; Szabó, Arnold; Németh, János; Völgyi, Béla

2017-08-01

Connexin36 (Cx36) constituent gap junctions (GJ) throughout the brain connect neurons into functional syncytia. In the retina they underlie the transmission, averaging and correlation of signals prior conveying visual information to the brain. This is the first study that describes retinal bipolar cell (BC) GJs in the human inner retina, whose function is enigmatic even in the examined animal models. Furthermore, a number of unique features (e.g. fovea, trichromacy, midget system) necessitate a reexamination of the animal model results in the human retina. Well-preserved postmortem human samples of this study are allowed to identify Cx36 expressing BCs neurochemically. Results reveal that both rod and cone pathway interneurons display strong Cx36 expression. Rod BC inputs to AII amacrine cells (AC) appear in juxtaposition to AII GJs, thus suggesting a strategic AII cell targeting by rod BCs. Cone BCs serving midget, parasol or koniocellular signaling pathways display a wealth of Cx36 expression to form homologously coupled arrays. In addition, they also establish heterologous GJ contacts to serve an exchange of information between parallel signaling streams. Interestingly, a prominent Cx36 expression was exhibited by midget system BCs that appear to maintain intimate contacts with bistratified BCs serving other pathways. These findings suggest that BC GJs in parallel signaling streams serve both an intra- and inter-pathway exchange of signals in the human retina.
Stem cell maintenance by manipulating signaling pathways: past, current and future

PubMed Central

Chen, Xi; Ye, Shoudong; Ying, Qi-Long

2015-01-01

Pluripotent stem cells only exist in a narrow window during early embryonic development, whereas multipotent stem cells are abundant throughout embryonic development and are retainedin various adult tissues and organs. While pluripotent stem cell lines have been established from several species, including mouse, rat, and human, it is still challenging to establish stable multipotent stem cell lines from embryonic or adult tissues. Based on current knowledge, we anticipate that by manipulating extrinsic and intrinsic signaling pathways, most if not all types of stem cells can be maintained in a long-term culture. In this article, we summarize current culture conditions established for the long-term maintenance of authentic pluripotent and multipotent stem cells and the signaling pathways involved. We also discuss the general principles of stem cell maintenance and propose several strategies on the establishment of novel stem cell lines through manipulation of signaling pathways. [BMB Reports 2015; 48(12): 668-676] PMID:26497581
Signaling Pathway in Early Brain Injury after Subarachnoid Hemorrhage: News Update.

PubMed

Ji, Chengyuan; Chen, Gang

2016-01-01

The annual incidence of subarachnoid hemorrhage (SAH) caused by intracranial aneurysm rupture is approximately 10.5/10 million people in China, making SAH the third most frequently occurring hemorrhage of the intracranial type after cerebral embolism and hypertensive intracerebral hemorrhage. SAH caused by ruptured aneurysm leads to a mortality rate as high as 67 %, and, because of the sudden onset of this disease, approximately 12-15 % of patients die before they can receive effective treatment. Early brain injury (EBI) is the brain damage occurring within the first 72 h after SAH. Two-thirds of mortality caused by SAH occurs within 48 h, mainly as a result of EBI. With the development of molecular biology and medicine microscopy techniques, various signaling pathways involved in EBI after SAH have been revealed. Understanding these signaling pathways may help clinicians treat EBI after SAH and improve long-term prognosis of SAH patients. This chapter summarizes several important signaling pathways implicated in EBI caused by SAH.
Inflammatory signaling pathways induced by Helicobacter pylori in primary human gastric epithelial cells.

PubMed

Tran, Cong Tri; Garcia, Magali; Garnier, Martine; Burucoa, Christophe; Bodet, Charles

2017-02-01

Inflammatory signaling pathways induced by Helicobacter pylori remain unclear, having been studied mostly on cell-line models derived from gastric adenocarcinoma with potentially altered signaling pathways and nonfunctional receptors. Here, H. pylori-induced signaling pathways were investigated in primary human gastric epithelial cells. Inflammatory response was analyzed on chemokine mRNA expression and production after infection of gastric epithelial cells by H. pylori strains, B128 and B128Δ cagM, a cag type IV secretion system defective strain. Signaling pathway involvement was investigated using inhibitors of epidermal growth factor receptor (EGFR), MAPK, JAK and blocking Abs against TLR2 and TLR4. Inhibitors of EGFR, MAPK and JAK significantly reduced the chemokine mRNA expression and production induced by both H. pylori strains at 3 h and 24 h post-infection. JNK inhibitor reduced chemokine production at 24 h post-infection. Blocking Abs against TLR2 but not TLR4 showed significant reduction of chemokine secretion. Using primary culture of human gastric epithelial cells, our data suggest that H. pylori can be recognized by TLR2, leading to chemokine induction, and that EGFR, MAPK and the JAK/STAT signaling pathways play a key role in the H. pylori-induced CXCL1, CXCL5 and CXCL8 response in a cag pathogenicity island-independent manner.
Wnt/β-catenin signaling pathway inhibits the proliferation and apoptosis of U87 glioma cells via different mechanisms

PubMed Central

Gao, Liyang; Chen, Bing; Li, Jinhong; Yang, Fan; Cen, Xuecheng; Liao, Zhuangbing; Long, Xiao’ao

2017-01-01

The Wnt signaling pathway is necessary for the development of the central nervous system and is associated with tumorigenesis in various cancers. However, the mechanism of the Wnt signaling pathway in glioma cells has yet to be elucidated. Small-molecule Wnt modulators such as ICG-001 and AZD2858 were used to inhibit and stimulate the Wnt/β-catenin signaling pathway. Techniques including cell proliferation assay, colony formation assay, Matrigel cell invasion assay, cell cycle assay and Genechip microarray were used. Gene Ontology Enrichment Analysis and Gene Set Enrichment Analysis have enriched many biological processes and signaling pathways. Both the inhibiting and stimulating Wnt/β-catenin signaling pathways could influence the cell cycle, moreover, reduce the proliferation and survival of U87 glioma cells. However, Affymetrix expression microarray indicated that biological processes and networks of signaling pathways between stimulating and inhibiting the Wnt/β-catenin signaling pathway largely differ. We propose that Wnt/β-catenin signaling pathway might prove to be a valuable therapeutic target for glioma. PMID:28837560
Halobenzoquinone-Induced Alteration of Gene Expression Associated with Oxidative Stress Signaling Pathways.

PubMed

Li, Jinhua; Moe, Birget; Liu, Yanming; Li, Xing-Fang

2018-06-05

Halobenzoquinones (HBQs) are emerging disinfection byproducts (DBPs) that effectively induce reactive oxygen species and oxidative damage in vitro. However, the impacts of HBQs on oxidative-stress-related gene expression have not been investigated. In this study, we examined alterations in the expression of 44 genes related to oxidative-stress-induced signaling pathways in human uroepithelial cells (SV-HUC-1) upon exposure to six HBQs. The results show the structure-dependent effects of HBQs on the studied gene expression. After 2 h of exposure, the expression levels of 9 to 28 genes were altered, while after 8 h of exposure, the expression levels of 29 to 31 genes were altered. Four genes ( HMOX1, NQO1, PTGS2, and TXNRD1) were significantly upregulated by all six HBQs at both exposure time points. Ingenuity pathway analysis revealed that the Nrf2 pathway was significantly responsive to HBQ exposure. Other canonical pathways responsive to HBQ exposure included GSH redox reductions, superoxide radical degradation, and xenobiotic metabolism signaling. This study has demonstrated that HBQs significantly alter the gene expression of oxidative-stress-related signaling pathways and contributes to the understanding of HBQ-DBP-associated toxicity.
Spatial separation of two different pathways accounting for the generation of calcium signals in astrocytes.

PubMed

Oschmann, Franziska; Mergenthaler, Konstantin; Jungnickel, Evelyn; Obermayer, Klaus

2017-02-01

Astrocytes integrate and process synaptic information and exhibit calcium (Ca2+) signals in response to incoming information from neighboring synapses. The generation of Ca2+ signals is mostly attributed to Ca2+ release from internal Ca2+ stores evoked by an elevated metabotropic glutamate receptor (mGluR) activity. Different experimental results associated the generation of Ca2+ signals to the activity of the glutamate transporter (GluT). The GluT itself does not influence the intracellular Ca2+ concentration, but it indirectly activates Ca2+ entry over the membrane. A closer look into Ca2+ signaling in different astrocytic compartments revealed a spatial separation of those two pathways. Ca2+ signals in the soma are mainly generated by Ca2+ release from internal Ca2+ stores (mGluR-dependent pathway). In astrocytic compartments close to the synapse most Ca2+ signals are evoked by Ca2+ entry over the plasma membrane (GluT-dependent pathway). This assumption is supported by the finding, that the volume ratio between the internal Ca2+ store and the intracellular space decreases from the soma towards the synapse. We extended a model for mGluR-dependent Ca2+ signals in astrocytes with the GluT-dependent pathway. Additionally, we included the volume ratio between the internal Ca2+ store and the intracellular compartment into the model in order to analyze Ca2+ signals either in the soma or close to the synapse. Our model results confirm the spatial separation of the mGluR- and GluT-dependent pathways along the astrocytic process. The model allows to study the binary Ca2+ response during a block of either of both pathways. Moreover, the model contributes to a better understanding of the impact of channel densities on the interaction of both pathways and on the Ca2+ signal.
MicroRNA and receptor mediated signaling pathways as potential therapeutic targets in heart failure.

PubMed

Tuttolomondo, Antonino; Simonetta, Irene; Pinto, Antonio

2016-11-01

Cardiac remodelling is a complex pathogenetic pathway involving genome expression, molecular, cellular, and interstitial changes that cause changes in size, shape and function of the heart after cardiac injury. Areas covered: We will review recent advances in understanding the role of several receptor-mediated signaling pathways and micro-RNAs, in addition to their potential as candidate target pathways in the pathogenesis of heart failure. The myocyte is the main target cell involved in the remodelling process via ischemia, cell necrosis and apoptosis (by means of various receptor pathways), and other mechanisms mediated by micro-RNAs. We will analyze the role of some receptor mediated signaling pathways such as natriuretic peptides, mediators of glycogen synthase kinase 3 and ERK1/2 pathways, beta-adrenergic receptor subtypes and relaxin receptor signaling mechanisms, TNF/TNF receptor family and TWEAK/Fn14 axis, and some micro-RNAs as candidate target pathways in pathogenesis of heart failure. These mediators of receptor-mediated pathways and micro-RNA are the most addressed targets of emerging therapies in modern heart failure treatment strategies. Expert opinion: Future treatment strategies should address mediators involved in multiple steps within heart failure pathogenetic pathways.
Multiple intracellular signaling pathways orchestrate adipocytic differentiation of human bone marrow stromal stem cells.

PubMed

Ali, Dalia; Abuelreich, Sarah; Alkeraishan, Nora; Shwish, Najla Bin; Hamam, Rimi; Kassem, Moustapha; Alfayez, Musaad; Aldahmash, Abdullah; Alajez, Nehad M

2018-02-28

Bone marrow adipocyte formation plays a role in bone homeostasis and whole body energy metabolism. However, the transcriptional landscape and signaling pathways associated with adipocyte lineage commitment and maturation are not fully delineated. Thus, we performed global gene expression profiling during adipocyte differentiation of human bone marrow stromal (mesenchymal) stem cells (hMSCs) and identified 2,589 up-regulated and 2,583 down-regulated mRNA transcripts. Pathway analysis on the up-regulated gene list untraveled enrichment in multiple signaling pathways including insulin receptor signaling, focal Adhesion, metapathway biotransformation, a number of metabolic pathways e.g. selenium metabolism, Benzo(a)pyrene metabolism, fatty acid, triacylglycerol, ketone body metabolism, tryptophan metabolism, and catalytic cycle of mammalian flavin-containing monooxygenase (FMOs). On the other hand, pathway analysis on the down-regulated genes revealed significant enrichment in pathways related to cell cycle regulation. Based on these data, we assessed the effect of pharmacological inhibition of FAK signaling using PF-573228, PF-562271, and InsR/IGF-1R using NVP-AEW541 and GSK-1904529A on adipocyte differentiation. hMSCs exposed to FAK or IGF-1R/InsR inhibitors exhibited fewer adipocyte formation (27-58% inhibition, P <0005). Concordantly, the expression of adipocyte-specific genes AP2, AdipoQ, and CEBPα was significantly reduced. On the other hand, we did not detect significant effects on cell viability as a result of FAK or IGF-1R/InsR inhibition. Our data identified FAK and insulin signaling as important intracellular signaling pathways relevant to bone marrow adipogenesis. © 2018 The Author(s).
Comparison of tumor related signaling pathways with known compounds to determine potential agents for lung adenocarcinoma.

PubMed

Xu, Song; Liu, Renwang; Da, Yurong

2018-06-05

This study compared tumor-related signaling pathways with known compounds to determine potential agents for lung adenocarcinoma (LUAD) treatment. Kyoto Encyclopedia of Genes and Genomes signaling pathway analyses were performed based on LUAD differentially expressed genes from The Cancer Genome Atlas (TCGA) project and genotype-tissue expression controls. These results were compared to various known compounds using the Connectivity Mapping dataset. The clinical significance of the hub genes identified by overlapping pathway enrichment analysis was further investigated using data mining from multiple sources. A drug-pathway network for LUAD was constructed, and molecular docking was carried out. After the integration of 57 LUAD-related pathways and 35 pathways affected by small molecules, five overlapping pathways were revealed. Among these five pathways, the p53 signaling pathway was the most significant, with CCNB1, CCNB2, CDK1, CDKN2A, and CHEK1 being identified as hub genes. The p53 signaling pathway is implicated as a risk factor for LUAD tumorigenesis and survival. A total of 88 molecules significantly inhibiting the five LUAD-related oncogenic pathways were involved in the LUAD drug-pathway network. Daunorubicin, mycophenolic acid, and pyrvinium could potentially target the hub gene CHEK1 directly. Our study highlights the critical pathways that should be targeted in the search for potential LUAD treatments, most importantly, the p53 signaling pathway. Some compounds, such as ciclopirox and AG-028671, may have potential roles for LUAD treatment but require further experimental verification. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Signal transduction in the wound response of tomato plants.

PubMed Central

Bowles, D

1998-01-01

The wound response of tomato plants has been extensively studied, and provides a useful model to understand signal transduction events leading from injury to marker gene expression. The principal markers that have been used in these studies are genes encoding proteinase inhibitor (pin) proteins. Activation of pin genes occurs in the wounded leaf and in distant unwounded leaves of the plant. This paper reviews current understanding of signalling pathways in the wounded leaf, and in the systemically responding unwounded leaves. First, the nature of known elicitors and their potential roles in planta are discussed, in particular, oligogalacturonides, jasmonates and the peptide signal, systemin. Inhibitors of wound-induced proteinase inhibitor (pin) expression are also reviewed, with particular reference to phenolics, sulphydryl reagents and fusicoccin. In each section, results obtained from the bioassay are considered within the wider context of data from mutants and from transgenic plants with altered levels of putative signalling components. Following this introduction, current models for pin gene regulation are described and discussed, together with a summary for the involvement of phosphorylation-dephosphorylation in wound signalling. Finally, a new model for wound-induced pin gene expression is presented, arising from recent data from the author's laboratory. PMID:9800210
Hippo Signaling in Mitosis: An Updated View in Light of the MEN Pathway.

PubMed

Hergovich, Alexander

2017-01-01

The Hippo pathway is an essential tumor suppressor signaling network that coordinates cell proliferation, death, and differentiation in higher eukaryotes. Intriguingly, the core components of the Hippo pathway are conserved from yeast to man, with the yeast analogs of mammalian MST1/2 (fly Hippo), MOB1 (fly Mats), LATS1/2 (fly Warts), and NDR1/2 (fly Tricornered) functioning as essential components of the mitotic exit network (MEN). Here, we update our previous summary of mitotic functions of Hippo core components in Drosophila melanogaster and mammals, with particular emphasis on similarities between the yeast MEN pathway and mitotic Hippo signaling. Mitotic functions of YAP and TAZ, the two main effectors of Hippo signaling, are also discussed.

Extrafloral nectar production of the ant-associated plant, Macaranga tanarius, is an induced, indirect, defensive response elicited by jasmonic acid

PubMed Central

Heil, Martin; Koch, Thomas; Hilpert, Andrea; Fiala, Brigitte; Boland, Wilhelm; Linsenmair, K. Eduard

2001-01-01

Plant species in at least 66 families produce extrafloral nectar (EFN) on their leaves or shoots and therewith attract predators and parasitoids, such as ants and wasps, which in turn defend them against herbivores. We investigated whether EFN secretion is induced by herbivory and/or artificial damage, and thus can be regarded as an induced defensive response. In addition, we studied the underlying signaling pathway. EFN secretion by field-grown Macaranga tanarius increased after herbivory, artificial leaf damage, and exogenous jasmonic acid (JA) application. Artificial damage strongly enhanced endogenous JA concentrations. The response in EFN production to artificial damage was much less pronounced in those leaves that were treated with phenidone to inhibit endogenous JA synthesis. Quantitative dose–response relations were found between the increase in nectar production and both the intensity of leaf damage and the amounts of exogenously applied JA. The amount of endogenously produced JA was positively correlated with the intensity of leaf damage. Increased numbers of defending insects and decreased numbers of herbivores were observed on leaves after inducing EFN production by exogenous JA treatment. Over 6 weeks, repeatedly applied JA or artificial damage resulted in a ten-fold reduction in herbivory. These results demonstrate that EFN production represents an alternative mechanism for induced, indirect defensive plant responses that are mediated via the octadecanoid signal transduction cascade. PMID:11158598
Crosstalk between the Notch signaling pathway and non-coding RNAs in gastrointestinal cancers

PubMed Central

Pan, Yangyang; Mao, Yuyan; Jin, Rong; Jiang, Lei

2018-01-01

The Notch signaling pathway is one of the main signaling pathways that mediates direct contact between cells, and is essential for normal development. It regulates various cellular processes, including cell proliferation, apoptosis, migration, invasion, angiogenesis and metastasis. It additionally serves an important function in tumor progression. Non-coding RNAs mainly include small microRNAs, long non-coding RNAs and circular RNAs. At present, a large body of literature supports the biological significance of non-coding RNAs in tumor progression. It is also becoming increasingly evident that cross-talk exists between Notch signaling and non-coding RNAs. The present review summarizes the current knowledge of Notch-mediated gastrointestinal cancer cell processes, and the effect of the crosstalk between the three major types of non-coding RNAs and the Notch signaling pathway on the fate of gastrointestinal cancer cells. PMID:29285185
Interleukin 4 signals through two related pathways.

PubMed

Pernis, A; Witthuhn, B; Keegan, A D; Nelms, K; Garfein, E; Ihle, J N; Paul, W E; Pierce, J H; Rothman, P

1995-08-15

The interleukin 4 (IL-4) signaling pathway involves activation, by tyrosine phosphorylation, of two distinct substrates, a signal-transducing factor (STF-IL4) and the IL-4-induced phosphotyrosine substrate (4PS). It is not known whether the IL-4-mediated activation of these substrates occurs via related or distinct signaling pathways. We report that 32D cells, an IL-3-dependent myeloid progenitor cell line in which no phosphorylated 4PS is found, activate high levels of STF-IL4 in response to IL-4. Consistent with the known requirement for 4PS or insulin receptor substrate 1 (IRS-1) in IL-4-mediated mitogenesis, activation of STF-IL4 in 32D cells is not sufficient for IL-4-inducible c-myc expression. In addition, we have examined the ability of 32D cells transfected with different truncation mutants of the human IL-4 receptor to activate Jak-3 kinase and STF-IL4 in response to human IL-4. As in the case of 4PS/IRS-1, we have found that activation of both Jak-3 and STF-IL4 requires the presence of the IL-4 receptor region comprising aa 437-557. The finding that the same region of the IL-4 receptor is required for the induction of both 4PS/IRS-1 and STF-IL4 suggests that the IL-4-stimulated activation of these two substrates might involve common factors.
Role of Nongenomic Signaling Pathways Activated by Aldosterone During Cardiac Reperfusion Injury.

PubMed

Ashton, Anthony W; Le, Thi Y L; Gomez-Sanchez, Celso E; Morel-Kopp, Marie-Christine; McWhinney, Brett; Hudson, Amanda; Mihailidou, Anastasia S

2015-08-01

Aldosterone (Aldo) activates both genomic and nongenomic signaling pathways in the cardiovascular system. Activation of genomic signaling pathways contributes to the adverse cardiac actions of Aldo during reperfusion injury; however, the extent nongenomic signaling pathways contribute has been difficult to identify due to lack of a specific ligand that activates only nongenomic signaling pathways. Using a pegylated aldosterone analog, aldosterone-3-carboxymethoxylamine-TFP ester conjugated to methoxypegylated amine (Aldo-PEG), we are able for the first time to distinguish between nongenomic and genomic cardiac actions of Aldo. We confirm Aldo-PEG activates phosphorylation of ERK1/2 in rat cardiomyocyte H9c2 cells similar to Aldo and G protein-coupled receptor 30 (GPR30 or GPER) agonist G1. GPER antagonist, G36, but not mineralocorticoid receptor (MR) antagonist spironolactone, prevented ERK1/2 phosphorylation by Aldo, Aldo-PEG, and G1. The selective nongenomic actions of Aldo-PEG are confirmed, with Aldo-PEG increasing superoxide production in H9c2 cells to similar levels as Aldo but having no effect on subcellular localization of MR. Striatin serves as a scaffold for GPER and MR, with GPER antagonist G36, but not spironolactone, restoring MR-striatin complexes. Aldo-PEG had no effect on MR-dependent transcriptional activation, whereas Aldo increased transcript levels of serum-regulated kinase 1 and plasminogen activator inhibitor-1. Using our ex vivo experimental rat model of myocardial infarction, we found aggravated infarct size and apoptosis by Aldo but not Aldo-PEG. Our studies confirm that in the heart, activation of nongenomic signaling pathways alone are not sufficient to trigger the deleterious effects of aldosterone during myocardial reperfusion injury.
Ties that bind: the integration of plastid signalling pathways in plant cell metabolism.

PubMed

Brunkard, Jacob O; Burch-Smith, Tessa M

2018-04-13

Plastids are critical organelles in plant cells that perform diverse functions and are central to many metabolic pathways. Beyond their major roles in primary metabolism, of which their role in photosynthesis is perhaps best known, plastids contribute to the biosynthesis of phytohormones and other secondary metabolites, store critical biomolecules, and sense a range of environmental stresses. Accordingly, plastid-derived signals coordinate a host of physiological and developmental processes, often by emitting signalling molecules that regulate the expression of nuclear genes. Several excellent recent reviews have provided broad perspectives on plastid signalling pathways. In this review, we will highlight recent advances in our understanding of chloroplast signalling pathways. Our discussion focuses on new discoveries illuminating how chloroplasts determine life and death decisions in cells and on studies elucidating tetrapyrrole biosynthesis signal transduction networks. We will also examine the role of a plastid RNA helicase, ISE2, in chloroplast signalling, and scrutinize intriguing results investigating the potential role of stromules in conducting signals from the chloroplast to other cellular locations. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
Proteomic analysis of the signaling pathway mediated by the heterotrimeric Gα protein Pga1 of Penicillium chrysogenum.

PubMed

Carrasco-Navarro, Ulises; Vera-Estrella, Rosario; Barkla, Bronwyn J; Zúñiga-León, Eduardo; Reyes-Vivas, Horacio; Fernández, Francisco J; Fierro, Francisco

2016-10-06

The heterotrimeric Gα protein Pga1-mediated signaling pathway regulates the entire developmental program in Penicillium chrysogenum, from spore germination to the formation of conidia. In addition it participates in the regulation of penicillin biosynthesis. We aimed to advance the understanding of this key signaling pathway using a proteomics approach, a powerful tool to identify effectors participating in signal transduction pathways. Penicillium chrysogenum mutants with different levels of activity of the Pga1-mediated signaling pathway were used to perform comparative proteomic analyses by 2D-DIGE and LC-MS/MS. Thirty proteins were identified which showed differences in abundance dependent on Pga1 activity level. By modifying the intracellular levels of cAMP we could establish cAMP-dependent and cAMP-independent pathways in Pga1-mediated signaling. Pga1 was shown to regulate abundance of enzymes in primary metabolic pathways involved in ATP, NADPH and cysteine biosynthesis, compounds that are needed for high levels of penicillin production. An in vivo phosphorylated protein containing a pleckstrin homology domain was identified; this protein is a candidate for signal transduction activity. Proteins with possible roles in purine metabolism, protein folding, stress response and morphogenesis were also identified whose abundance was regulated by Pga1 signaling. Thirty proteins whose abundance was regulated by the Pga1-mediated signaling pathway were identified. These proteins are involved in primary metabolism, stress response, development and signal transduction. A model describing the pathways through which Pga1 signaling regulates different cellular processes is proposed.
CD147 regulates extrinsic apoptosis in spermatocytes by modulating NFκB signaling pathways

PubMed Central

Wang, Chaoqun; Fok, Kin Lam; Cai, Zhiming; Chen, Hao; Chan, Hsiao Chang

2017-01-01

CD147 null mutant male mice are infertile with arrested spermatogenesis and increased apoptotic germ cells. Our previous studies have shown that CD147 prevents apoptosis in mouse spermatocytes but not spermatogonia. However, the underlying mechanism remains elusive. In the present study, we aim to determine the CD147-regulated apoptotic pathway in mouse spermatocytes. Our results showed that immunodepletion of CD147 triggered apoptosis through extrinsic apoptotic pathway in mouse testis and spermatocyte cell line (GC-2 cells), accompanied by activation of non-canonical NFκB signaling and suppression of canonical NFκB signaling. Furthermore, CD147 was found to interact with TRAF2, a factor known to regulate NFκB and extrinsic apoptotic signaling, and interfering CD147 led to the decrease of TRAF2. Consistently, depletion of CD147 by CRISPR/Cas9 technique in GC-2 cells down-regulated TRAF2 and resulted in cell death with suppressed canonical NFκB and activated non-canonical NFκB signaling. On the contrary, interfering of CD147 had no effect on NFκB signaling pathways as well as TRAF2 protein level in mouse spermatogonia cell line (GC-1 cells). Taken together, these results suggested that CD147 plays a key role in reducing extrinsic apoptosis in spermatocytes, but not spermatogonia, through modulating NFκB signaling pathway. PMID:27902973
CD147 regulates extrinsic apoptosis in spermatocytes by modulating NFκB signaling pathways.

PubMed

Wang, Chaoqun; Fok, Kin Lam; Cai, Zhiming; Chen, Hao; Chan, Hsiao Chang

2017-01-10

CD147 null mutant male mice are infertile with arrested spermatogenesis and increased apoptotic germ cells. Our previous studies have shown that CD147 prevents apoptosis in mouse spermatocytes but not spermatogonia. However, the underlying mechanism remains elusive. In the present study, we aim to determine the CD147-regulated apoptotic pathway in mouse spermatocytes. Our results showed that immunodepletion of CD147 triggered apoptosis through extrinsic apoptotic pathway in mouse testis and spermatocyte cell line (GC-2 cells), accompanied by activation of non-canonical NFκB signaling and suppression of canonical NFκB signaling. Furthermore, CD147 was found to interact with TRAF2, a factor known to regulate NFκB and extrinsic apoptotic signaling, and interfering CD147 led to the decrease of TRAF2. Consistently, depletion of CD147 by CRISPR/Cas9 technique in GC-2 cells down-regulated TRAF2 and resulted in cell death with suppressed canonical NFκB and activated non-canonical NFκB signaling. On the contrary, interfering of CD147 had no effect on NFκB signaling pathways as well as TRAF2 protein level in mouse spermatogonia cell line (GC-1 cells). Taken together, these results suggested that CD147 plays a key role in reducing extrinsic apoptosis in spermatocytes, but not spermatogonia, through modulating NFκB signaling pathway.
Signaling mechanisms underlying the robustness and tunability of the plant immune network

PubMed Central

Kim, Yungil; Tsuda, Kenichi; Igarashi, Daisuke; Hillmer, Rachel A.; Sakakibara, Hitoshi; Myers, Chad L.; Katagiri, Fumiaki

2014-01-01

Summary How does robust and tunable behavior emerge in a complex biological network? We sought to understand this for the signaling network controlling pattern-triggered immunity (PTI) in Arabidopsis. A dynamic network model containing four major signaling sectors, the jasmonate, ethylene, PAD4, and salicylate sectors, which together explain up to 80% of the PTI level, was built using data for dynamic sector activities and PTI levels under exhaustive combinatorial sector perturbations. Our regularized multiple regression model had a high level of predictive power and captured known and unexpected signal flows in the network. The sole inhibitory sector in the model, the ethylene sector, was central to the network robustness via its inhibition of the jasmonate sector. The model's multiple input sites linked specific signal input patterns varying in strength and timing to different network response patterns, indicating a mechanism enabling tunability. PMID:24439900
Attraction of New Zealand flower thrips, Thrips obscuratus, to cis-jasmone, a volatile identified from Japanese honeysuckle flowers.

PubMed

El-Sayed, A M; Mitchell, V J; McLaren, G F; Manning, L M; Bunn, B; Suckling, D M

2009-06-01

This work was undertaken to identify floral compound(s) produced by honeysuckle flowers, Lonicera japonica (Thunberg), that mediate the attraction of New Zealand flower thrips Thrips obscuratus (Crawford). Volatiles were collected during the day and night and analyzed by gas chromatography-mass spectrometry (GC-MS) to determine their emission over these two periods. Nine compounds were identified in the headspace; the main compound was linalool, and the other compounds were germacrene D, E,E-alpha-farnesene, nerolidol, cis-jasmone, cis-3-hexenyl acetate, hexyl acetate, cis-hexenyl tiglate, and indole. There was a quantitative difference between day and night volatiles, with cis-3-hexenyl acetate, hexyl acetate, cis-hexenyl tiglate, and cis-jasmone emitted in higher amounts during the day compared to the night. When the compounds were tested individually in field trapping experiments, only cis-jasmone attracted New Zealand flower thrips in a significant number. In another field trapping experiment, cis-jasmone caught similar numbers of New Zealand flower thrips compared to a floral blend formulated to mimic the ratios of the compounds emitted during the day, while catch with the night-emitted floral blend was not significantly different from the control. Subsequently, two field trapping experiments were conducted to determine the optimal attraction dose for cis-jasmone, a range of 1-100 mg loaded onto a red rubber stopper was tested, and the highest catches were in traps baited with 100 mg loading. A higher range of 100-1000 mg loaded into polyethylene vials was tested, and the highest catch was in traps baited with 500 mg. In another experiment aimed at comparing the attraction efficacy of cis-jasmone with the two other known thrips attractants (ethyl nicotinate and p-anisaldehyde), ethyl nicotinate showed the highest trap catch followed by cis-jasmone. A smaller number of Thrips tabaci (Lindeman) was attracted to traps baited with cis-jasmone. These results
Natural Genetic Variation Influences Protein Abundances in C. elegans Developmental Signalling Pathways

PubMed Central

Singh, Kapil Dev; Roschitzki, Bernd; Snoek, L. Basten; Grossmann, Jonas; Zheng, Xue; Elvin, Mark; Kamkina, Polina; Schrimpf, Sabine P.; Poulin, Gino B.; Kammenga, Jan E.; Hengartner, Michael O.

2016-01-01

Complex traits, including common disease-related traits, are affected by many different genes that function in multiple pathways and networks. The apoptosis, MAPK, Notch, and Wnt signalling pathways play important roles in development and disease progression. At the moment we have a poor understanding of how allelic variation affects gene expression in these pathways at the level of translation. Here we report the effect of natural genetic variation on transcript and protein abundance involved in developmental signalling pathways in Caenorhabditis elegans. We used selected reaction monitoring to analyse proteins from the abovementioned four pathways in a set of recombinant inbred lines (RILs) generated from the wild-type strains N2 (Bristol) and CB4856 (Hawaii) to enable quantitative trait locus (QTL) mapping. About half of the cases from the 44 genes tested showed a statistically significant change in protein abundance between various strains, most of these were however very weak (below 1.3-fold change). We detected a distant QTL on the left arm of chromosome II that affected protein abundance of the phosphatidylserine receptor protein PSR-1, and two separate QTLs that influenced embryonic and ionizing radiation-induced apoptosis on chromosome IV. Our results demonstrate that natural variation in C. elegans is sufficient to cause significant changes in signalling pathways both at the gene expression (transcript and protein abundance) and phenotypic levels. PMID:26985669
A special pair of phytohormones controls excitability, slow closure, and external stomach formation in the Venus flytrap

PubMed Central

Escalante-Pérez, María; Krol, Elzbieta; Stange, Annette; Geiger, Dietmar; Al-Rasheid, Khaled A. S.; Hause, Bettina; Neher, Erwin; Hedrich, Rainer

2011-01-01

Venus flytrap's leaves can catch an insect in a fraction of a second. Since the time of Charles Darwin, scientists have struggled to understand the sensory biology and biomechanics of this plant, Dionaea muscipula. Here we show that insect-capture of Dionaea traps is modulated by the phytohormone abscisic acid (ABA) and jasmonates. Water-stressed Dionaea, as well as those exposed to the drought-stress hormone ABA, are less sensitive to mechanical stimulation. In contrast, application of 12-oxo-phytodienoic acid (OPDA), a precursor of the phytohormone jasmonic acid (JA), the methyl ester of JA (Me-JA), and coronatine (COR), the molecular mimic of the isoleucine conjugate of JA (JA-Ile), triggers secretion of digestive enzymes without any preceding mechanical stimulus. Such secretion is accompanied by slow trap closure. Under physiological conditions, insect-capture is associated with Ca2+ signaling and a rise in OPDA, Apparently, jasmonates bypass hapto-electric processes associated with trap closure. However, ABA does not affect OPDA-dependent gland activity. Therefore, signals for trap movement and secretion seem to involve separate pathways. Jasmonates are systemically active because application to a single trap induces secretion and slow closure not only in the given trap but also in all others. Furthermore, formerly touch-insensitive trap sectors are converted into mechanosensitive ones. These findings demonstrate that prey-catching Dionaea combines plant-specific signaling pathways, involving OPDA and ABA with a rapidly acting trigger, which uses ion channels, action potentials, and Ca2+ signals. PMID:21896747
A special pair of phytohormones controls excitability, slow closure, and external stomach formation in the Venus flytrap.

PubMed

Escalante-Pérez, María; Krol, Elzbieta; Stange, Annette; Geiger, Dietmar; Al-Rasheid, Khaled A S; Hause, Bettina; Neher, Erwin; Hedrich, Rainer

2011-09-13

Venus flytrap's leaves can catch an insect in a fraction of a second. Since the time of Charles Darwin, scientists have struggled to understand the sensory biology and biomechanics of this plant, Dionaea muscipula. Here we show that insect-capture of Dionaea traps is modulated by the phytohormone abscisic acid (ABA) and jasmonates. Water-stressed Dionaea, as well as those exposed to the drought-stress hormone ABA, are less sensitive to mechanical stimulation. In contrast, application of 12-oxo-phytodienoic acid (OPDA), a precursor of the phytohormone jasmonic acid (JA), the methyl ester of JA (Me-JA), and coronatine (COR), the molecular mimic of the isoleucine conjugate of JA (JA-Ile), triggers secretion of digestive enzymes without any preceding mechanical stimulus. Such secretion is accompanied by slow trap closure. Under physiological conditions, insect-capture is associated with Ca(2+) signaling and a rise in OPDA, Apparently, jasmonates bypass hapto-electric processes associated with trap closure. However, ABA does not affect OPDA-dependent gland activity. Therefore, signals for trap movement and secretion seem to involve separate pathways. Jasmonates are systemically active because application to a single trap induces secretion and slow closure not only in the given trap but also in all others. Furthermore, formerly touch-insensitive trap sectors are converted into mechanosensitive ones. These findings demonstrate that prey-catching Dionaea combines plant-specific signaling pathways, involving OPDA and ABA with a rapidly acting trigger, which uses ion channels, action potentials, and Ca(2+) signals.
Molecular mechanism of TGF-β signaling pathway in colon carcinogenesis and status of curcumin as chemopreventive strategy.

PubMed

Ramamoorthi, Ganesan; Sivalingam, Nageswaran

2014-08-01

Colon cancer is one of the third most common cancer in man, the second most common cancer in women worldwide, and the second leading cause of mortality in the USA. There are a number of molecular pathways that have been implicated in colon carcinogenesis, including TGF-β/Smad signaling pathway. TGF-β (transforming growth factor-beta) signaling pathway has the potential to regulate various biological processes including cell growth, differentiation, apoptosis, extracellular matrix modeling, and immune response. TGF-β signaling pathway acts as a tumor suppressor, but alterations in TGF-β signaling pathway promotes colon cancer cell growth, migration, invasion, angiogenesis, and metastasis. Here we review the role of TGF-β signaling cascade in colon carcinogenesis and multiple molecular targets of curcumin in colon carcinogenesis. Elucidation of the molecular mechanism of curcumin on TGF-β signaling pathway-induced colon carcinogenesis may ultimately lead to novel and more effective treatments for colon cancer.
Gene profiling of the red light signalling pathways in roots.

PubMed

Molas, Maria Lia; Kiss, John Z; Correll, Melanie J

2006-01-01

Red light, acting through the phytochromes, controls numerous aspects of plant development. Many of the signal transduction elements downstream of the phytochromes have been identified in the aerial portions of the plant; however, very few elements in red-light signalling have been identified specifically for roots. Gene profiling studies using microarrays and quantitative Real-Time PCR were performed to characterize gene expression changes in roots of Arabidopsis seedlings exposed to 1 h of red light. Several factors acting downstream of phytochromes in red-light signalling in roots were identified. Some of the genes found to be differentially expressed in this study have already been characterized in the red-light-signalling pathway for whole plants. For example, PHYTOCHROME KINASE 1 (PKS1), LONG HYPOCOTYL 5 (HY5), EARLY FLOWERING 4 (ELF4), and GIGANTEA (GI) were all significantly up-regulated in roots of seedlings exposed to 1 h of red light. The up-regulation of SUPPRESSOR OF PHYTOCHROME A RESPONSES 1 (SPA1) and CONSTITUTIVE PHOTOMORPHOGENIC 1-like (COP1-like) genes suggests that the PHYA-mediated pathway was attenuated by red light. In addition, genes involved in lateral root and root hair formation, root plastid development, phenylpropanoid metabolism, and hormone signalling were also regulated by exposure to red light. Interestingly, members of the RPT2/NPH3 (ROOT PHOTOTROPIC 2/NON PHOTOTROPIC HYPOCOTYL 3) family, which have been shown to mediate blue-light-induced phototropism, were also differentially regulated in roots in red light. Therefore, these results suggest that red and blue light pathways interact in roots of seedlings and that many elements involved in red-light-signalling found in the aerial portions of the plant are differentially expressed in roots within 1 h of red light exposure.
A liquid chromatography/electrospray ionisation tandem mass spectrometry method for the simultaneous quantification of salicylic, jasmonic and abscisic acids in Coffea arabica leaves.

PubMed

de Sá, Marta; Ferreira, João P; Queiroz, Vagner T; Vilas-Boas, Luís; Silva, Maria C; Almeida, Maria H; Guerra-Guimarães, Leonor; Bronze, Maria R

2014-02-01

Plants have developed an efficient system of recognition that induces a complex network of signalling molecules such as salicylic acid (SA), jasmonic acid (JA) and abscisic acid (ABA) in case of a pathogenic infection. The use of specific and sensitive methods is mandatory for the analysis of compounds in these complex samples. In this study a liquid chromatography/electrospray ionisation tandem mass spectrometry method was developed and validated for the simultaneous quantification of SA, JA and ABA in Coffea arabica (L.) leaves in order to understand the role of these phytohormones in the signalling network involved in the coffee defence response against Hemileia vastatrix. The results showed that the method was specific, linear (r ≥ 0.99) in the range 0.125-1.00 µg mL⁻¹ for JA and ABA and 0.125-5.00 µg mL⁻¹ for SA, and precise (relative standard deviation ≤11%), and the limit of detection (0.010 µg g⁻¹ fresh weight) was adequate for quantifying these phytohormones in this type of matrix. In comparison with healthy leaves, those infected with H. vastatrix (resistance reaction) displayed an increase in SA level 24 h after inoculation, suggesting the involvement of an SA-dependent pathway in coffee resistance. © 2013 Society of Chemical Industry.
Adapting the Stress Response: Viral Subversion of the mTOR Signaling Pathway.

PubMed

Le Sage, Valerie; Cinti, Alessandro; Amorim, Raquel; Mouland, Andrew J

2016-05-24

The mammalian target of rapamycin (mTOR) is a central regulator of gene expression, translation and various metabolic processes. Multiple extracellular (growth factors) and intracellular (energy status) molecular signals as well as a variety of stressors are integrated into the mTOR pathway. Viral infection is a significant stress that can activate, reduce or even suppress the mTOR signaling pathway. Consequently, viruses have evolved a plethora of different mechanisms to attack and co-opt the mTOR pathway in order to make the host cell a hospitable environment for replication. A more comprehensive knowledge of different viral interactions may provide fruitful targets for new antiviral drugs.
Adapting the Stress Response: Viral Subversion of the mTOR Signaling Pathway

PubMed Central

Le Sage, Valerie; Cinti, Alessandro; Amorim, Raquel; Mouland, Andrew J.

2016-01-01

The mammalian target of rapamycin (mTOR) is a central regulator of gene expression, translation and various metabolic processes. Multiple extracellular (growth factors) and intracellular (energy status) molecular signals as well as a variety of stressors are integrated into the mTOR pathway. Viral infection is a significant stress that can activate, reduce or even suppress the mTOR signaling pathway. Consequently, viruses have evolved a plethora of different mechanisms to attack and co-opt the mTOR pathway in order to make the host cell a hospitable environment for replication. A more comprehensive knowledge of different viral interactions may provide fruitful targets for new antiviral drugs. PMID:27231932
Interplay between sugar and hormone signaling pathways modulate floral signal transduction

PubMed Central

Matsoukas, Ianis G.

2014-01-01

NOMENCLATURE The following nomenclature will be used in this article: Names of genes are written in italicized upper-case letters, e.g., ABI4.Names of proteins are written in non-italicized upper-case letters, e.g., ABI4.Names of mutants are written in italicized lower-case letters, e.g., abi4. The juvenile-to-adult and vegetative-to-reproductive phase transitions are major determinants of plant reproductive success and adaptation to the local environment. Understanding the intricate molecular genetic and physiological machinery by which environment regulates juvenility and floral signal transduction has significant scientific and economic implications. Sugars are recognized as important regulatory molecules that regulate cellular activity at multiple levels, from transcription and translation to protein stability and activity. Molecular genetic and physiological approaches have demonstrated different aspects of carbohydrate involvement and its interactions with other signal transduction pathways in regulation of the juvenile-to-adult and vegetative-to-reproductive phase transitions. Sugars regulate juvenility and floral signal transduction through their function as energy sources, osmotic regulators and signaling molecules. Interestingly, sugar signaling has been shown to involve extensive connections with phytohormone signaling. This includes interactions with phytohormones that are also important for the orchestration of developmental phase transitions, including gibberellins, abscisic acid, ethylene, and brassinosteroids. This article highlights the potential roles of sugar-hormone interactions in regulation of floral signal transduction, with particular emphasis on Arabidopsis thaliana mutant phenotypes, and suggests possible directions for future research. PMID:25165468
Interplay between sugar and hormone signaling pathways modulate floral signal transduction.

PubMed

Matsoukas, Ianis G

2014-01-01

NOMENCLATURE The following nomenclature will be used in this article: Names of genes are written in italicized upper-case letters, e.g., ABI4.Names of proteins are written in non-italicized upper-case letters, e.g., ABI4.Names of mutants are written in italicized lower-case letters, e.g., abi4. The juvenile-to-adult and vegetative-to-reproductive phase transitions are major determinants of plant reproductive success and adaptation to the local environment. Understanding the intricate molecular genetic and physiological machinery by which environment regulates juvenility and floral signal transduction has significant scientific and economic implications. Sugars are recognized as important regulatory molecules that regulate cellular activity at multiple levels, from transcription and translation to protein stability and activity. Molecular genetic and physiological approaches have demonstrated different aspects of carbohydrate involvement and its interactions with other signal transduction pathways in regulation of the juvenile-to-adult and vegetative-to-reproductive phase transitions. Sugars regulate juvenility and floral signal transduction through their function as energy sources, osmotic regulators and signaling molecules. Interestingly, sugar signaling has been shown to involve extensive connections with phytohormone signaling. This includes interactions with phytohormones that are also important for the orchestration of developmental phase transitions, including gibberellins, abscisic acid, ethylene, and brassinosteroids. This article highlights the potential roles of sugar-hormone interactions in regulation of floral signal transduction, with particular emphasis on Arabidopsis thaliana mutant phenotypes, and suggests possible directions for future research.

A Transgenerational Endocrine Signaling Pathway in Crustacea

PubMed Central

LeBlanc, Gerald A.; Wang, Ying H.; Holmes, Charisse N.; Kwon, Gwijun; Medlock, Elizabeth K.

2013-01-01

Background Environmental signals to maternal organisms can result in developmental alterations in progeny. One such example is environmental sex determination in Branchiopod crustaceans. We previously demonstrated that the hormone methyl farnesoate could orchestrate environmental sex determination in the early embryo to the male phenotype. Presently, we identify a transcription factor that is activated by methyl farnesoate and explore the extent and significance of this transgenerational signaling pathway. Methodology/Principal Findings Several candidate transcription factors were cloned from the water flea Daphnia pulex and evaluated for activation by methyl farnesoate. One of the factors evaluated, the complex of two bHLH-PAS proteins, dappuMet and SRC, activated a reporter gene in response to methyl farnesoate. Several juvenoid compounds were definitively evaluated for their ability to activate this receptor complex (methyl farnesoate receptor, MfR) in vitro and stimulate male sex determination in vivo. Potency to activate the MfR correlated to potency to stimulate male sex determination of offspring (pyriproxyfen>methyl farnesoate>methoprene, kinoprene). Daphnids were exposed to concentrations of pyriproxyfen and physiologic responses determined over multiple generations. Survivial, growth, and sex of maternal organisms were not affected by pyriproxyfen exposure. Sex ratio among offspring (generation 2) were increasingly skewed in favor of males with increasing pyriproxyfen concentration; while, the number of offspring per brood was progressively reduced. Female generation 2 daphnids were reared to reproductive maturity in the absence of pyriproxyfen. Sex ratios of offspring (generation 3) were not affected in this pyriproxyfen lineage, however, the number of offspring per brood, again, was significantly reduced. Conclusions Results reveal likely components to a hormone/receptor signaling pathway in a crustacean that orchestrates transgenerational modifications
UNDERSTANDING PATHWAYS OF TOXICITY: MAKING SENSE OF CHANGING SIGNALS

EPA Science Inventory

Title:
Understanding Pathways of Toxicity: Making sense of changing signals
Authors & affiliations:
Sid Hunter, Maria Blanton, Edward Karoly, Ellen Rogers, Leonard Mole, Phillip Hartig, James Andrews. Reproductive Toxicology Division, National Health and Environmental Ef...
Neuroglian activates Echinoid to antagonize the Drosophila EGF receptor signaling pathway.

PubMed

Islam, Rafique; Wei, Shu-Yi; Chiu, Wei-Hsin; Hortsch, Michael; Hsu, Jui-Chou

2003-05-01

echinoid (ed) encodes an cell-adhesion molecule (CAM) that contains immunoglobulin domains and regulates the EGFR signaling pathway during Drosophila eye development. Based on our previous genetic mosaic and epistatic analysis, we proposed that Ed, via homotypic interactions, activates a novel, as yet unknown pathway that antagonizes EGFR signaling. In this report, we demonstrate that Ed functions as a homophilic adhesion molecule and also engages in a heterophilic trans-interaction with Drosophila Neuroglian (Nrg), an L1-type CAM. Co-expression of ed and nrg in the eye exhibits a strong genetic synergy in inhibiting EGFR signaling. This synergistic effect requires the intracellular domain of Ed, but not that of Nrg. In addition, Ed and Nrg colocalize in the Drosophila eye and are efficiently co-immunoprecipitated. Together, our results suggest a model in which Nrg acts as a heterophilic ligand and activator of Ed, which in turn antagonizes EGFR signaling.
Jasmonic Acid Enhances Al-Induced Root Growth Inhibition1[OPEN

PubMed Central

Yang, Zhong-Bao; Ma, Yanqi

2017-01-01

Phytohormones such as ethylene and auxin are involved in the regulation of the aluminum (Al)-induced root growth inhibition. Although jasmonate (JA) has been reported to play a crucial role in the regulation of root growth and development in response to environmental stresses through interplay with ethylene and auxin, its role in the regulation of root growth response to Al stress is not yet known. In an attempt to elucidate the role of JA, we found that exogenous application of JA enhanced the Al-induced root growth inhibition. Furthermore, phenotype analysis with mutants defective in either JA biosynthesis or signaling suggests that JA is involved in the regulation of Al-induced root growth inhibition. The expression of the JA receptor CORONATINE INSENSITIVE1 (COI1) and the key JA signaling regulator MYC2 was up-regulated in response to Al stress in the root tips. This process together with COI1-mediated Al-induced root growth inhibition under Al stress was controlled by ethylene but not auxin. Transcriptomic analysis revealed that many responsive genes under Al stress were regulated by JA signaling. The differential responsive of microtubule organization-related genes between the wild-type and coi1-2 mutant is consistent with the changed depolymerization of cortical microtubules in coi1 under Al stress. In addition, ALMT-mediated malate exudation and thus Al exclusion from roots in response to Al stress was also regulated by COI1-mediated JA signaling. Together, this study suggests that root growth inhibition is regulated by COI1-mediated JA signaling independent from auxin signaling and provides novel insights into the phytohormone-mediated root growth inhibition in response to Al stress. PMID:27932419
C-Jun N-terminal kinase signalling pathway in response to cisplatin.

PubMed

Yan, Dong; An, GuangYu; Kuo, Macus Tien

2016-11-01

Cisplatin (cis diamminedichloroplatinum II, cDDP) is one of the most effective cancer chemotherapeutic agents and is used in the treatment of many types of human malignancies. However, inherent tumour resistance is a major barrier to effective cisplatin therapy. So far, the mechanism of cDDP resistance has not been well defined. In general, cisplatin is considered to be a cytotoxic drug, for damaging DNA and inhibiting DNA synthesis, resulting in apoptosis via the mitochondrial death pathway or plasma membrane disruption. cDDP-induced DNA damage triggers signalling pathways that will eventually decide between cell life and death. As a member of the mitogen-activated protein kinases family, c-Jun N-terminal kinase (JNK) is a signalling pathway in response to extracellular stimuli, especially drug treatment, to modify the activity of numerous proteins locating in the mitochondria or the nucleus. Recent studies suggest that JNK signalling pathway plays a major role in deciding the fate of the cell and inducing resistance to cDDP-induced apoptosis in human tumours. c-Jun N-terminal kinase regulates several important cellular functions including cell proliferation, differentiation, survival and apoptosis while activating and inhibiting substrates for phosphorylation transcription factors (c-Jun, ATF2: Activating transcription factor 2, p53 and so on), which subsequently induce pro-apoptosis and pro-survival factors expression. Therefore, it is suggested that JNK signal pathway is a double-edged sword in cDDP treatment, simultaneously being a significant pro-apoptosis factor but also being associated with increased resistance to cisplatin-based chemotherapy. This review focuses on current knowledge concerning the role of JNK in cell response to cDDP, as well as their role in cisplatin resistance. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
Molecular pathways of platelet factor 4/CXCL4 signaling.

PubMed

Kasper, Brigitte; Petersen, Frank

2011-01-01

The platelet-derived chemokine CXCL4 takes a specific and unique position within the family of chemotactic cytokines. Today, much attention is directed to CXCL4's capacity to inhibit angiogenesis and to promote innate immune responses, which makes this chemokine an interesting tool and target for potential intervention in tumor growth and inflammation. However, such attempts demand a comprehensive knowledge on the molecular mechanisms and pathways underlying the corresponding cellular functions. At least two structurally different receptors, CXCR3-B and a chondroitin sulfate proteoglycan, are capable of binding CXCL4 and to induce a specific intracellular signaling machinery. While signaling mediated by CXCR3-B involves Gs proteins, elevated cAMP levels, and p38 MAP kinase, signaling via proteoglycans appears to be more complicated and varies strongly between the cell types analyzed. In CXCL4-activated neutrophils and monocytes, tyrosine kinases of the Src family and Syk as well as monomeric GTPases and members of the MAP kinase family have been identified as essential intracellular signals. Most intriguingly, signaling does not proceed in a linear sequence of events but in a repeated activation of certain transducing elements like Rac2 or sphingosine kinase 1. Depending on the downstream targets, such biphasic kinetics either leads to a redundant and prolonged activation of a single pathway or to a timely separated initiation of disparate signals and functions. Results of the studies reviewed here help to understand the molecular basis of CXCL4's functional diversity and provide insights into integrated signaling processes in general. Copyright © 2011 Elsevier GmbH. All rights reserved.
Why does anatabine, but not nicotine, accumulate in jasmonate-elicited cultured tobacco BY-2 cells?

PubMed

Shoji, Tsubasa; Hashimoto, Takashi

2008-08-01

Suspension-cultured cells of Nicotiana tabacum cv. Bright Yellow-2 (BY-2) grow rapidly in a highly homogenous population and still exhibit the general behavior of plant cells, and thus are often used as model systems in several areas of plant molecular and cellular biology, including secondary metabolism. While the parental tobacco variety synthesizes nicotine as a major alkaloid, the cultured tobacco cells mainly produce a related alkaloid anatabine, instead of nicotine, when elicited with jasmonates. We report here that cultured BY-2 cells scarcely express N-methylputrescine oxidase (MPO) genes even after jasmonate elicitation. MPO is the second enzyme in the biosynthetic pathway that supplies the pyrrolidine moiety of nicotine and nornicotine, but is predicted to be dispensable for the biosynthesis of anatabine, anabasine and anatalline, which do not contain the pyrrolidine moiety. When MPO was overexpressed in tobacco BY-2 cells, nicotine synthesis was dramatically enhanced while anatabine formation was effectively suppressed. As a complementary approach, we suppressed MPO expression by RNA interference in tobacco hairy roots that normally accumulate nicotine. In the MPO-suppressed roots, the contents of anatabine, anabasine and anatalline, as well as N-methylputrescine and putrescine, markedly increased to compensate for suppressed formation of nicotine and nornicotine. These results identify the transcriptional regulation of MPO as a critical rate-limiting step that restricts nicotine formation in cultured tobacco BY-2 cells.
Activation of ethylene signaling pathways enhances disease resistance by regulating ROS and phytoalexin production in rice.

PubMed

Yang, Chao; Li, Wen; Cao, Jidong; Meng, Fanwei; Yu, Yongqi; Huang, Junkai; Jiang, Lan; Liu, Muxing; Zhang, Zhengguang; Chen, Xuewei; Miyamoto, Koji; Yamane, Hisakazu; Zhang, Jinsong; Chen, Shouyi; Liu, Jun

2017-01-01

Ethylene plays diverse roles in plant growth, development and stress responses. However, the roles of ethylene signaling in immune responses remain largely unknown. In this study, we showed that the blast fungus Magnaporthe oryzae infection activated ethylene biosynthesis in rice. Resistant rice cultivars accumulated higher levels of ethylene than susceptible ones. Ethylene signaling components OsEIN2 and the downstream transcription factor OsEIL1 positively regulated disease resistance. Mutation of OsEIN2 led to enhanced disease susceptibility. Whole-genome transcription analysis revealed that responsive genes of ethylene, jasmonates (JAs) and reactive oxygen species (ROS) signaling as well as phytoalexin biosynthesis genes were remarkably induced. Transcription of OsrbohA/B, which encode NADPH oxidases, and OsOPRs, the JA biosynthesis genes, were induced by M. oryzae infection. Furthermore, we demonstrated that OsEIL1 binds to the promoters of OsrbohA/OsrbohB and OsOPR4 to activate their expression. These data suggest that OsEIN2-mediated OsrbohA/OsrbohB and OsOPR transcription may play essential roles in ROS generation, JA biosynthesis and the subsequent phytoalexin accumulation. Therefore, the involvement of ethylene signaling in disease resistance is probably by activation of ROS and phytoalexin production in rice during M. oryzae infection. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.
Comparative transcriptional profiling of Gracilariopsis lemaneiformis in response to salicylic acid- and methyl jasmonate-mediated heat resistance

PubMed Central

Wang, Chongbin; Zou, Tonglei; Xu, Nianjun; Sun, Xue

2017-01-01

Culturing the economically important macroalga Gracilariopsis lemaneiformis (Rhodophyta) is limited due to the high temperatures in the summertime on the southern Chinese coast. Previous studies have demonstrated that two phytohormones, salicylic acid (SA) and methyl jasmonate (MJ), can alleviate the adverse effects of high-temperature stress on Gp. lemaneiformis. To elucidate the molecular mechanisms underlying SA- and MJ-mediated heat tolerance, we performed comprehensive analyses of transcriptome-wide gene expression profiles using RNA sequencing (RNA-seq) technology. A total of 14,644 unigenes were assembled, and 10,501 unigenes (71.71%) were annotated to the reference databases. In the SA, MJ and SA/MJ treatment groups, 519, 830, and 974 differentially expressed unigenes were detected, respectively. Unigenes related to photosynthesis and glycometabolism were enriched by SA, while unigenes associated with glycometabolism, protein synthesis, heat shock and signal transduction were increased by MJ. A crosstalk analysis revealed that 216 genes were synergistically regulated, while 18 genes were antagonistically regulated by SA and MJ. The results indicated that the two phytohormones could mitigate the adverse effects of heat on multiple pathways, and they predominantly acted synergistically to resist heat stress. These results will provide new insights into how SA and MJ modulate the molecular mechanisms that counteract heat stress in algae. PMID:28464018
Tofacitinib Represses the Janus Kinase-Signal Transducer and Activators of Transcription Signalling Pathway in Keratinocytes.

PubMed

Srivastava, Ankit; Ståhle, Mona; Pivarcsi, Andor; Sonkoly, Enikö

2018-05-08

Tofacitinib is a Janus kinase (JAK) inhibitor, which has shown efficacy in treating psoriasis. The mode of action of tofacitinib is not completely understood but it has been thought to be mediated by the inhibition of CD4+ T-cell activation. Here, we investigated whether the molecular targets of tofacitinib are expressed in keratinocytes, and whether tofacitinib can modulate the activity of the JAK/Signal Transducer and Activators of Transcription (STAT)-pathway in keratinocytes. Transcriptomic profiling of human keratinocytes treated with IL-22 in combination with tofacitinib revealed that tofacitinib could prevent the majority of IL-22-mediated gene expression changes. Pathway analysis of tofacitinib-regulated genes in keratinocytes revealed enrichment of genes involved in the JAK/STAT signalling pathway. Quantitative real-time-PCR confirmed the upregulation of S100A7 and downregulation of EGR1 expression by IL-22, which was prevented by tofacitinib pre-treatment. These results indicate a direct effect of tofacinitib on keratinocytes, which can have relevance for systemic as well as for topical treatment of psoriasis with tofacitinib.
Drosophila Nociceptive Sensitization Requires BMP Signaling via the Canonical SMAD Pathway.

PubMed

Follansbee, Taylor L; Gjelsvik, Kayla J; Brann, Courtney L; McParland, Aidan L; Longhurst, Colin A; Galko, Michael J; Ganter, Geoffrey K

2017-08-30

Nociceptive sensitization is a common feature in chronic pain, but its basic cellular mechanisms are only partially understood. The present study used the Drosophila melanogaster model system and a candidate gene approach to identify novel components required for modulation of an injury-induced nociceptive sensitization pathway presumably downstream of Hedgehog. This study demonstrates that RNAi silencing of a member of the Bone Morphogenetic Protein (BMP) signaling pathway, Decapentaplegic (Dpp), specifically in the Class IV multidendritic nociceptive neuron, significantly attenuated ultraviolet injury-induced sensitization. Furthermore, overexpression of Dpp in Class IV neurons was sufficient to induce thermal hypersensitivity in the absence of injury. The requirement of various BMP receptors and members of the SMAD signal transduction pathway in nociceptive sensitization was also demonstrated. The effects of BMP signaling were shown to be largely specific to the sensitization pathway and not associated with changes in nociception in the absence of injury or with changes in dendritic morphology. Thus, the results demonstrate that Dpp and its pathway play a crucial and novel role in nociceptive sensitization. Because the BMP family is so strongly conserved between vertebrates and invertebrates, it seems likely that the components analyzed in this study represent potential therapeutic targets for the treatment of chronic pain in humans. SIGNIFICANCE STATEMENT This report provides a genetic analysis of primary nociceptive neuron mechanisms that promote sensitization in response to injury. Drosophila melanogaster larvae whose primary nociceptive neurons were reduced in levels of specific components of the BMP signaling pathway, were injured and then tested for nocifensive responses to a normally subnoxious stimulus. Results suggest that nociceptive neurons use the BMP2/4 ligand, along with identified receptors and intracellular transducers to transition to a
Xtalk: a path-based approach for identifying crosstalk between signaling pathways

PubMed Central

Tegge, Allison N.; Sharp, Nicholas; Murali, T. M.

2016-01-01

Motivation: Cells communicate with their environment via signal transduction pathways. On occasion, the activation of one pathway can produce an effect downstream of another pathway, a phenomenon known as crosstalk. Existing computational methods to discover such pathway pairs rely on simple overlap statistics. Results: We present Xtalk, a path-based approach for identifying pairs of pathways that may crosstalk. Xtalk computes the statistical significance of the average length of multiple short paths that connect receptors in one pathway to the transcription factors in another. By design, Xtalk reports the precise interactions and mechanisms that support the identified crosstalk. We applied Xtalk to signaling pathways in the KEGG and NCI-PID databases. We manually curated a gold standard set of 132 crosstalking pathway pairs and a set of 140 pairs that did not crosstalk, for which Xtalk achieved an area under the receiver operator characteristic curve of 0.65, a 12% improvement over the closest competing approach. The area under the receiver operator characteristic curve varied with the pathway, suggesting that crosstalk should be evaluated on a pathway-by-pathway level. We also analyzed an extended set of 658 pathway pairs in KEGG and to a set of more than 7000 pathway pairs in NCI-PID. For the top-ranking pairs, we found substantial support in the literature (81% for KEGG and 78% for NCI-PID). We provide examples of networks computed by Xtalk that accurately recovered known mechanisms of crosstalk. Availability and implementation: The XTALK software is available at http://bioinformatics.cs.vt.edu/~murali/software. Crosstalk networks are available at http://graphspace.org/graphs?tags=2015-bioinformatics-xtalk. Contact: ategge@vt.edu, murali@cs.vt.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26400040
Is the canonical RAF-MEK-ERK signaling pathway a therapeutic target in SCLC?

PubMed Central

Cristea, Sandra; Sage, Julien

2017-01-01

The activity of the RAF-MEK-ERK signaling pathway is critical for the proliferation of normal and cancerous cells. Oncogenic mutations driving the development of lung adenocarcinoma often activate this signaling pathway. In contrast, pathway activity levels and their biological roles are not well established in small cell lung cancer (SCLC), a fast-growing neuroendocrine lung cancer subtype. Here we discuss the function of the RAF-MEK-ERK kinase pathway and the mechanisms leading to its activation in SCLC cells. In particular, we argue that activation of this pathway may be beneficial to the survival, proliferation and spread of SCLC cells in response to multiple stimuli. We also consider evidence that high levels of RAF-MEK-ERK pathway activity may be detrimental to SCLC tumors, including in part by interfering with their neuroendocrine fate. Based on these observations, we examine when small molecules targeting kinases in the RAF-MEK-ERK pathway may be useful therapeutically in SCLC patients, including in combination with other therapeutic agents. PMID:27133774
Aberrant Signaling Pathways in T-Cell Acute Lymphoblastic Leukemia

PubMed Central

Bongiovanni, Deborah; Saccomani, Valentina

2017-01-01

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease caused by the malignant transformation of immature progenitors primed towards T-cell development. Clinically, T-ALL patients present with diffuse infiltration of the bone marrow by immature T-cell blasts high blood cell counts, mediastinal involvement, and diffusion to the central nervous system. In the past decade, the genomic landscape of T-ALL has been the target of intense research. The identification of specific genomic alterations has contributed to identify strong oncogenic drivers and signaling pathways regulating leukemia growth. Notwithstanding, T-ALL patients are still treated with high-dose multiagent chemotherapy, potentially exposing these patients to considerable acute and long-term side effects. This review summarizes recent advances in our understanding of the signaling pathways relevant for the pathogenesis of T-ALL and the opportunities offered for targeted therapy. PMID:28872614
SNIP1: a new activator of HSE signaling pathway.

PubMed

Li, Qiang; An, Jian; Liu, Xianghua; Zhang, Mingjun; Ling, Yichen; Wang, Chenji; Zhao, Jing; Yu, Long

2012-03-01

In the last 10 years, more and more attention has been focused on SNIP1 (Smad nuclear interacting protein 1), which functions as a transcriptional coactivator. We report here that through quantitative real-time PCR analysis in 18 different human tissues, SNIP1 was found to be expressed ubiquitously. When overexpressed in HeLa cells, SNIP1-EGFP fused protein exhibited a nuclear localization with a characteristic subnuclear distribution in speckles or formed larger discrete nuclear bodies in some cells. Reporter gene assay showed that overexpression of SNIP1 in HEK 293 cells or H1299 cells strongly activated the HSE signaling pathway. Moreover, SNIP1 could selectively regulate the transcription of HSP70A1A and HSP27. Taken together, our findings suggest that SNIP1 might also be a positive regulator of HSE signaling pathway.
Pattern-recognition receptors: signaling pathways and dysregulation in canine chronic enteropathies-brief review.

PubMed

Heilmann, Romy M; Allenspach, Karin

2017-11-01

Pattern-recognition receptors (PRRs) are expressed by innate immune cells and recognize pathogen-associated molecular patterns (PAMPs) as well as endogenous damage-associated molecular pattern (DAMP) molecules. With a large potential for synergism or convergence between their signaling pathways, PRRs orchestrate a complex interplay of cellular mediators and transcription factors, and thus play a central role in homeostasis and host defense. Aberrant activation of PRR signaling, mutations of the receptors and/or their downstream signaling molecules, and/or DAMP/PAMP complex-mediated receptor signaling can potentially lead to chronic auto-inflammatory diseases or development of cancer. PRR signaling pathways appear to also present an interesting new avenue for the modulation of inflammatory responses and to serve as potential novel therapeutic targets. Evidence for a dysregulation of the PRR toll-like receptor (TLR)2, TLR4, TLR5, and TLR9, nucleotide-binding oligomerization domain-containing protein (NOD)2, and the receptor of advanced glycation end products (RAGE) exists in dogs with chronic enteropathies. We describe the TLR, NOD2, and RAGE signaling pathways and evaluate the current veterinary literature-in comparison to human medicine-to determine the role of TLRs, NOD2, and RAGE in canine chronic enteropathies.
Ecological trade-offs between jasmonic acid-dependent direct and indirect plant defences in tritrophic interactions

PubMed Central

Wei, Jianing; Wang, Lizhong; Zhao, Jiuhai; Li, Chuanyou; Ge, Feng; Kang, Le

2011-01-01

Recent studies on plants genetically modified in jasmonic acid (JA) signalling support the hypothesis that the jasmonate family of oxylipins plays an important role in mediating direct and indirect plant defences. However, the interaction of two modes of defence in tritrophic systems is largely unknown. In this study, we examined the preference and performance of a herbivorous leafminer (Liriomyza huidobrensis) and its parasitic wasp (Opius dissitus) on three tomato genotypes: a wild-type (WT) plant, a JA biosynthesis (spr2) mutant, and a JA-overexpression 35S::prosys plant. Their proteinase inhibitor production and volatile emission were used as direct and indirect defence factors to evaluate the responses of leafminers and parasitoids. Here, we show that although spr2 mutant plants are compromised in direct defence against the larval leafminers and in attracting parasitoids, they are less attractive to adult flies compared with WT plants. Moreover, in comparison to other genotypes, the 35S::prosys plant displays greater direct and constitutive indirect defences, but reduced success of parasitism by parasitoids. Taken together, these results suggest that there are distinguished ecological trade-offs between JA-dependent direct and indirect defences in genetically modified plants whose fitness should be assessed in tritrophic systems and under natural conditions. PMID:21039561
Overexpression of aryl hydrocarbon receptor (AHR) signalling pathway in human meningioma.

PubMed

Talari, Noble Kumar; Panigrahi, Manas K; Madigubba, Sailaja; Phanithi, Prakash Babu

2018-04-01

Aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor and involved in tumorigenesis of many cancers. However there are no reports on AHR in human meningioma. Therefore we examined the status of the AHR and its signalling molecules in human meningioma by using tumor biopsy samples and autopsy control meninges. We report the up regulation of AHR pathway genes like aryl hydrocarbon receptor nuclear translocator (ARNT), aldehyde dehydrogenase1family memberA3 (ALDH1A3), cytochrome P450, family1, subfamily A polypeptide1 (CYP1A1) and TCCD induced poly ADP ribose polymerase (TIPARP) gene expression in human meningioma. Further, AHR protein expression was found to be up regulated in all grades of human meningioma. We found that AHR localized in the nucleus for high grade anaplastic meningioma through immunohistochemical analysis. Since AHR signalling pathway was known to involve in inhibition of apoptosis in cancer cells, we evaluated the cyclophilin D levels which maintains mitochondrial permeability transition pore a critical event during apoptosis. We report that cyclophilin D levels were upregulated in all grades of human meningioma compared to control meninges. Finally we also evaluated c-Fos protein levels as its levels were regulated by AHR. Here we report that c-Fos protein levels were down regulated in all grades of human meningioma compared to control meninges. To sum-up we found that AHR signalling pathway components were upregulated, as the grade of the meningioma progresses from low to high grade, suggesting an important role of AHR signalling pathway in human meningioma.
Dysregulation of Uterine Signaling Pathways in Progesterone Receptor-Cre Knockout of Dicer

PubMed Central

Andreu-Vieyra, Claudia V.; Kim, Tae Hoon; Jeong, Jae-Wook; Hodgson, Myles C.; Chen, Ruihong; Creighton, Chad J.; Lydon, John P.; Gunaratne, Preethi H.; DeMayo, Francesco J.; Matzuk, Martin M.

2012-01-01

Epithelial-stromal interactions in the uterus are required for normal uterine functions such as pregnancy, and multiple signaling pathways are essential for this process. Although Dicer and microRNA (miRNA) have been implicated in several reproductive processes, the specific roles of Dicer and miRNA in uterine development are not known. To address the roles of miRNA in the regulation of key uterine pathways, we generated a conditional knockout of Dicer in the postnatal uterine epithelium and stroma using progesterone receptor-Cre. These Dicer conditional knockout females are sterile with small uteri, which demonstrate significant defects, including absence of glandular epithelium and enhanced stromal apoptosis, beginning at approximately postnatal d 15, with coincident expression of Cre and deletion of Dicer. Specific miRNA (miR-181c, −200b, −101, let-7d) were down-regulated and corresponding predicted proapoptotic target genes (Bcl2l11, Aldh1a3) were up-regulated, reflecting the apoptotic phenomenon. Although these mice had normal serum hormone levels, critical uterine signaling pathways, including progesterone-responsive genes, Indian hedgehog signaling, and the Wnt/β-catenin canonical pathway, were dysregulated at the mRNA level. Importantly, uterine stromal cell proliferation in response to progesterone was absent, whereas uterine epithelial cell proliferation in response to estradiol was maintained in adult uteri. These data implicate Dicer and appropriate miRNA expression as essential players in the regulation of multiple uterine signaling pathways required for uterine development and appropriate function. PMID:22798293
ERK signaling pathway regulates sleep duration through activity-induced gene expression during wakefulness.

PubMed

Mikhail, Cyril; Vaucher, Angélique; Jimenez, Sonia; Tafti, Mehdi

2017-01-24

Wakefulness is accompanied by experience-dependent synaptic plasticity and an increase in activity-regulated gene transcription. Wake-induced genes are certainly markers of neuronal activity and may also directly regulate the duration of and need for sleep. We stimulated murine cortical cultures with the neuromodulatory signals that are known to control wakefulness in the brain and found that norepinephrine alone or a mixture of these neuromodulators induced activity-regulated gene transcription. Pharmacological inhibition of the various signaling pathways involved in the regulation of gene expression indicated that the extracellular signal-regulated kinase (ERK) pathway is the principal one mediating the effects of waking neuromodulators on gene expression. In mice, ERK phosphorylation in the cortex increased and decreased with wakefulness and sleep. Whole-body or cortical neuron-specific deletion of Erk1 or Erk2 significantly increased the duration of wakefulness in mice, and pharmacological inhibition of ERK phosphorylation decreased sleep duration and increased the duration of wakefulness bouts. Thus, this signaling pathway, which is highly conserved from Drosophila to mammals, is a key pathway that links waking experience-induced neuronal gene expression to sleep duration and quality. Copyright © 2017, American Association for the Advancement of Science.

Identification of Major Signaling Pathways in Prion Disease Progression Using Network Analysis

PubMed Central

Newaz, Khalique; Sriram, K.; Bera, Debajyoti

2015-01-01

Prion diseases are transmissible neurodegenerative diseases that arise due to conformational change of normal, cellular prion protein (PrPC) to protease-resistant isofrom (rPrPSc). Deposition of misfolded PrpSc proteins leads to an alteration of many signaling pathways that includes immunological and apoptotic pathways. As a result, this culminates in the dysfunction and death of neuronal cells. Earlier works on transcriptomic studies have revealed some affected pathways, but it is not clear which is (are) the prime network pathway(s) that change during the disease progression and how these pathways are involved in crosstalks with each other from the time of incubation to clinical death. We perform network analysis on large-scale transcriptomic data of differentially expressed genes obtained from whole brain in six different mouse strain-prion strain combination models to determine the pathways involved in prion diseases, and to understand the role of crosstalks in disease propagation. We employ a notion of differential network centrality measures on protein interaction networks to identify the potential biological pathways involved. We also propose a crosstalk ranking method based on dynamic protein interaction networks to identify the core network elements involved in crosstalk with different pathways. We identify 148 DEGs (differentially expressed genes) potentially related to the prion disease progression. Functional association of the identified genes implicates a strong involvement of immunological pathways. We extract a bow-tie structure that is potentially dysregulated in prion disease. We also propose an ODE model for the bow-tie network. Predictions related to diseased condition suggests the downregulation of the core signaling elements (PI3Ks and AKTs) of the bow-tie network. In this work, we show using transcriptomic data that the neuronal dysfunction in prion disease is strongly related to the immunological pathways. We conclude that these
Astaxanthin induces angiogenesis through Wnt/β-catenin signaling pathway.

PubMed

Xu, Yangyang; Zhang, Jie; Jiang, Wanglin; Zhang, Shuping

2015-07-15

In the present study, we sought to elucidate whether astaxanthin contributes to induce angiogenesis and its mechanisms. To this end, we examined the role of astaxanthin on human brain microvascular endothelial cell line (HBMEC) and rat aortic smooth muscle cell (RASMC) proliferation, invasion and tube formation in vitro. For study of mechanism, the Wnt/β-catenin signaling pathway inhibitor IWR-1-endo was used. HMBECs and RASMCs proliferation were tested by cell counting. Scratch adhesion test was used to assess the ability of invasion. A matrigel tube formation assay was performed to test capillary tube formation ability. The Wnt/β-catenin pathway activation in HMBECs and RASMCs were tested by Western blot. Our data suggested that astaxanthin induces angiogenesis by increasing proliferation, invasion and tube formation in vitro. Wnt and β-catenin expression were increased by astaxanthin and counteracted by IWR-1-endo in HMBECs and RASMCs. Tube formation was increased by astaxanthin and counteracted by IWR-1-endo. It may be suggested that astaxanthin induces angiogenesis in vitro via a programmed Wnt/β-catenin signaling pathway. Copyright © 2015 Elsevier GmbH. All rights reserved.
Interleukin 4 signals through two related pathways.

PubMed Central

Pernis, A; Witthuhn, B; Keegan, A D; Nelms, K; Garfein, E; Ihle, J N; Paul, W E; Pierce, J H; Rothman, P

1995-01-01

The interleukin 4 (IL-4) signaling pathway involves activation, by tyrosine phosphorylation, of two distinct substrates, a signal-transducing factor (STF-IL4) and the IL-4-induced phosphotyrosine substrate (4PS). It is not known whether the IL-4-mediated activation of these substrates occurs via related or distinct signaling pathways. We report that 32D cells, an IL-3-dependent myeloid progenitor cell line in which no phosphorylated 4PS is found, activate high levels of STF-IL4 in response to IL-4. Consistent with the known requirement for 4PS or insulin receptor substrate 1 (IRS-1) in IL-4-mediated mitogenesis, activation of STF-IL4 in 32D cells is not sufficient for IL-4-inducible c-myc expression. In addition, we have examined the ability of 32D cells transfected with different truncation mutants of the human IL-4 receptor to activate Jak-3 kinase and STF-IL4 in response to human IL-4. As in the case of 4PS/IRS-1, we have found that activation of both Jak-3 and STF-IL4 requires the presence of the IL-4 receptor region comprising aa 437-557. The finding that the same region of the IL-4 receptor is required for the induction of both 4PS/IRS-1 and STF-IL4 suggests that the IL-4-stimulated activation of these two substrates might involve common factors. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:7544011
Evolutionary Proteomics Uncovers Ancient Associations of Cilia with Signaling Pathways.

PubMed

Sigg, Monika Abedin; Menchen, Tabea; Lee, Chanjae; Johnson, Jeffery; Jungnickel, Melissa K; Choksi, Semil P; Garcia, Galo; Busengdal, Henriette; Dougherty, Gerard W; Pennekamp, Petra; Werner, Claudius; Rentzsch, Fabian; Florman, Harvey M; Krogan, Nevan; Wallingford, John B; Omran, Heymut; Reiter, Jeremy F

2017-12-18

Cilia are organelles specialized for movement and signaling. To infer when during evolution signaling pathways became associated with cilia, we characterized the proteomes of cilia from sea urchins, sea anemones, and choanoflagellates. We identified 437 high-confidence ciliary candidate proteins conserved in mammals and discovered that Hedgehog and G-protein-coupled receptor pathways were linked to cilia before the origin of bilateria and transient receptor potential (TRP) channels before the origin of animals. We demonstrated that candidates not previously implicated in ciliary biology localized to cilia and further investigated ENKUR, a TRP channel-interacting protein identified in the cilia of all three organisms. ENKUR localizes to motile cilia and is required for patterning the left-right axis in vertebrates. Moreover, mutation of ENKUR causes situs inversus in humans. Thus, proteomic profiling of cilia from diverse eukaryotes defines a conserved ciliary proteome, reveals ancient connections to signaling, and uncovers a ciliary protein that underlies development and human disease. Copyright © 2017 Elsevier Inc. All rights reserved.
Conditions and constraints for astrocyte calcium signaling in the hippocampal mossy fiber pathway

PubMed Central

Haustein, Martin D.; Kracun, Sebastian; Lu, Xiao-Hong; Shih, Tiffany; Jackson-Weaver, Olan; Tong, Xiaoping; Xu, Ji; Yang, X. William; O'Dell, Thomas J.; Marvin, Jonathan S.; Ellisman, Mark H.; Bushong, Eric A.; Looger, Loren L.; Khakh, Baljit S.

2014-01-01

Summary The spatiotemporal activities of astrocyte Ca2+ signaling in mature neuronal circuits remain unclear. We used genetically encoded Ca2+ and glutamate indicators as well as pharmacogenetic and electrical control of neurotransmitter release to explore astrocyte activity in the hippocampal mossy fiber pathway. Our data revealed numerous localised spontaneous Ca2+ signals in astrocyte branches and territories, but these were not driven by neuronal activity or glutamate. Moreover, evoked astrocyte Ca2+ signaling changed linearly with the number of mossy fiber action potentials. Under these settings astrocyte responses were global, suppressed by neurotransmitter clearance and mediated by glutamate and GABA. Thus, astrocyte engagement in the fully developed mossy fiber pathway was slow and territorial, contrary to that frequently proposed for astrocytes within microcircuits. We show that astrocyte Ca2+ signaling functionally segregates large volumes of neuropil and that these transients are not suited for responding to, or regulating, single synapses in the mossy fiber pathway. PMID:24742463
Association of Wnt1-inducible signaling pathway protein-1 with the proliferation, migration and invasion in gastric cancer cells.

PubMed

Jia, Shuqin; Qu, Tingting; Feng, Mengmeng; Ji, Ke; Li, Ziyu; Jiang, Wenguo; Ji, Jiafu

2017-06-01

Wnt1-inducible signaling pathway protein-1 is a cysteine-rich protein that belongs to the CCN family, which has been implicated in mediating the occurrence and progression through distinct molecular mechanisms in several tumor types. However, the association of Wnt1-inducible signaling pathway protein-1 with gastric cancer and the related molecular mechanisms remain to be elucidated. Therefore, this study aimed to clarify the biological role of Wnt1-inducible signaling pathway protein-1 in the proliferation, migration, and invasion in gastric cancer cells and further investigated the associated molecular mechanism on these biological functions. We first detected the expression level of Wnt1-inducible signaling pathway protein-1 in gastric cancer, and the reverse transcription polymerase chain reaction have shown that Wnt1-inducible signaling pathway protein-1 expression levels were upregulated in gastric cancer tissues. The expression of Wnt1-inducible signaling pathway protein-1 in gastric cancer cell lines was also detected by quantitative real-time polymerase chain reaction and Western blotting. Furthermore, two gastric cancer cell lines with high expression of Wnt1-inducible signaling pathway protein-1 were selected to explore the biological function of Wnt1-inducible signaling pathway protein-1 in gastric cancer. Function assays indicated that knockdown of Wnt1-inducible signaling pathway protein-1 suppressed cell proliferation, migration, and invasion in BGC-823 and AGS gastric cancer cells. Further investigation of mechanisms suggested that cyclinD1 was identified as one of Wnt1-inducible signaling pathway protein-1 related genes to accelerate proliferation in gastric cancer cells. In addition, one pathway of Wnt1-inducible signaling pathway protein-1 induced migration and invasion was mainly through the enhancement of epithelial-to-mesenchymal transition progression. Taken together, our findings presented the first evidence that Wnt1-inducible signaling
Bile Acid Signaling Pathways from the Enterohepatic Circulation to the Central Nervous System

PubMed Central

Mertens, Kim L.; Kalsbeek, Andries; Soeters, Maarten R.; Eggink, Hannah M.

2017-01-01

Bile acids are best known as detergents involved in the digestion of lipids. In addition, new data in the last decade have shown that bile acids also function as gut hormones capable of influencing metabolic processes via receptors such as FXR (farnesoid X receptor) and TGR5 (Takeda G protein-coupled receptor 5). These effects of bile acids are not restricted to the gastrointestinal tract, but can affect different tissues throughout the organism. It is still unclear whether these effects also involve signaling of bile acids to the central nervous system (CNS). Bile acid signaling to the CNS encompasses both direct and indirect pathways. Bile acids can act directly in the brain via central FXR and TGR5 signaling. In addition, there are two indirect pathways that involve intermediate agents released upon interaction with bile acids receptors in the gut. Activation of intestinal FXR and TGR5 receptors can result in the release of fibroblast growth factor 19 (FGF19) and glucagon-like peptide 1 (GLP-1), both capable of signaling to the CNS. We conclude that when plasma bile acids levels are high all three pathways may contribute in signal transmission to the CNS. However, under normal physiological circumstances, the indirect pathway involving GLP-1 may evoke the most substantial effect in the brain. PMID:29163019
Targeting the intracellular signaling "STOP" and "GO" pathways for the treatment of alcohol use disorders.

PubMed

Ron, Dorit; Berger, Anthony

2018-06-01

In recent years, research has identified the molecular and neural substrates underlying the transition of moderate "social" consumption of alcohol to the characteristic alcohol use disorder (AUD) phenotypes including excessive and compulsive alcohol use which we define in the review as the GO signaling pathways. In addition, growing evidence points to the existence of molecular mechanisms that keep alcohol consumption in check and that confer resilience for the development of AUD which we define herein as the STOP signaling pathways. In this review, we focus on examples of the GO and the STOP intracellular signaling pathways and discuss our current knowledge of how manipulations of these pathways may be used for the treatment of AUD.
Core signaling pathways in ovarian cancer stem cell revealed by integrative analysis of multi-marker genomics data.

PubMed

Zhang, Tianyu; Xu, Jielin; Deng, Siyuan; Zhou, Fengqi; Li, Jin; Zhang, Liwei; Li, Lang; Wang, Qi-En; Li, Fuhai

2018-01-01

Tumor recurrence occurs in more than 70% of ovarian cancer patients, and the majority eventually becomes refractory to treatments. Ovarian Cancer Stem Cells (OCSCs) are believed to be responsible for the tumor relapse and drug resistance. Therefore, eliminating ovarian CSCs is important to improve the prognosis of ovarian cancer patients. However, there is a lack of effective drugs to eliminate OCSCs because the core signaling pathways regulating OCSCs remain unclear. Also it is often hard for biologists to identify a few testable targets and infer driver signaling pathways regulating CSCs from a large number of differentially expression genes in an unbiased manner. In this study, we propose a straightforward and integrative analysis to identify potential core signaling pathways of OCSCs by integrating transcriptome data of OCSCs isolated based on two distinctive markers, ALDH and side population, with regulatory network (Transcription Factor (TF) and Target Interactome) and signaling pathways. We first identify the common activated TFs in two OCSC populations integrating the gene expression and TF-target Interactome; and then uncover up-stream signaling cascades regulating the activated TFs. In specific, 22 activated TFs are identified. Through literature search validation, 15 of them have been reported in association with cancer stem cells. Additionally, 10 TFs are found in the KEGG signaling pathways, and their up-stream signaling cascades are extracted, which also provide potential treatment targets. Moreover, 40 FDA approved drugs are identified to target on the up-stream signaling cascades, and 15 of them have been reported in literatures in cancer stem cell treatment. In conclusion, the proposed approach can uncover the activated up-stream signaling, activated TFs and up-regulated target genes that constitute the potential core signaling pathways of ovarian CSC. Also drugs and drug combinations targeting on the core signaling pathways might be able to
Differential Costs of Two Distinct Resistance Mechanisms Induced by Different Herbivore Species in Arabidopsis1

PubMed Central

Reichelt, Michael; van Doorn, Arjen; Schuurink, Robert C.

2016-01-01

Plants respond to herbivory with the induction of resistance, mediated by distinct phytohormonal signaling pathways and their interactions. Phloem feeders are known to induce plant resistance via the salicylic acid pathway, whereas biting-chewing herbivores induce plant resistance mainly via the jasmonate pathway. Here, we show that a specialist caterpillar (biting-chewing herbivore) and a specialist aphid (phloem feeder) differentially induce resistance against Pieris brassicae caterpillars in Arabidopsis (Arabidopsis thaliana) plants. Caterpillar feeding induces resistance through the jasmonate signaling pathway that is associated with the induction of kaempferol 3,7-dirhamnoside, whereas aphid feeding induces resistance via a novel mechanism involving sinapoyl malate. The role of sinapoyl malate is confirmed through the use of a mutant compromised in the biosynthesis of this compound. Caterpillar-induced resistance is associated with a lower cost in terms of plant growth reduction than aphid-induced resistance. A strong constitutive resistance against P. brassicae caterpillars in combination with a strong growth attenuation in plants of a transfer DNA (T-DNA) insertion mutant of WRKY70 (wrky70) suggest that the WRKY70 transcription factor, a regulator of downstream responses mediated by jasmonate-salicylic acid signaling cross talk, is involved in the negative regulation of caterpillar resistance and in the tradeoff between growth and defense. In conclusion, different mechanisms of herbivore-induced resistance come with different costs, and a functional WRKY70 transcription factor is required for the induction of low-cost resistance. PMID:26603653
Understanding disease mechanisms with models of signaling pathway activities.

PubMed

Sebastian-Leon, Patricia; Vidal, Enrique; Minguez, Pablo; Conesa, Ana; Tarazona, Sonia; Amadoz, Alicia; Armero, Carmen; Salavert, Francisco; Vidal-Puig, Antonio; Montaner, David; Dopazo, Joaquín

2014-10-25

Understanding the aspects of the cell functionality that account for disease or drug action mechanisms is one of the main challenges in the analysis of genomic data and is on the basis of the future implementation of precision medicine. Here we propose a simple probabilistic model in which signaling pathways are separated into elementary sub-pathways or signal transmission circuits (which ultimately trigger cell functions) and then transforms gene expression measurements into probabilities of activation of such signal transmission circuits. Using this model, differential activation of such circuits between biological conditions can be estimated. Thus, circuit activation statuses can be interpreted as biomarkers that discriminate among the compared conditions. This type of mechanism-based biomarkers accounts for cell functional activities and can easily be associated to disease or drug action mechanisms. The accuracy of the proposed model is demonstrated with simulations and real datasets. The proposed model provides detailed information that enables the interpretation disease mechanisms as a consequence of the complex combinations of altered gene expression values. Moreover, it offers a framework for suggesting possible ways of therapeutic intervention in a pathologically perturbed system.
Phospholipase D Signaling Pathways and Phosphatidic Acid as Therapeutic Targets in Cancer

PubMed Central

Bruntz, Ronald C.; Lindsley, Craig W.

2014-01-01

Phospholipase D is a ubiquitous class of enzymes that generates phosphatidic acid as an intracellular signaling species. The phospholipase D superfamily plays a central role in a variety of functions in prokaryotes, viruses, yeast, fungi, plants, and eukaryotic species. In mammalian cells, the pathways modulating catalytic activity involve a variety of cellular signaling components, including G protein–coupled receptors, receptor tyrosine kinases, polyphosphatidylinositol lipids, Ras/Rho/ADP-ribosylation factor GTPases, and conventional isoforms of protein kinase C, among others. Recent findings have shown that phosphatidic acid generated by phospholipase D plays roles in numerous essential cellular functions, such as vesicular trafficking, exocytosis, autophagy, regulation of cellular metabolism, and tumorigenesis. Many of these cellular events are modulated by the actions of phosphatidic acid, and identification of two targets (mammalian target of rapamycin and Akt kinase) has especially highlighted a role for phospholipase D in the regulation of cellular metabolism. Phospholipase D is a regulator of intercellular signaling and metabolic pathways, particularly in cells that are under stress conditions. This review provides a comprehensive overview of the regulation of phospholipase D activity and its modulation of cellular signaling pathways and functions. PMID:25244928
The Role of the Wnt/β-catenin Signaling Pathway in Formation and Maintenance of Bone and Teeth

PubMed Central

Duan, Peipei; Bonewald, LF

2016-01-01

The Wnt signaling pathway is known as one of the important molecular cascades that regulate cell fate throughout lifespan. The Wnt signaling pathway is further separated into the canonical signaling pathway that depends on the function of β-catenin (Wnt/β-catenin pathway) and the noncanonical pathways that operate independently of β-catenin (planar cell polarity pathway and Wnt/Ca2+ pathway). The Wnt/β-catenin signaling pathway is complex and consists of numerous receptors, inhibitors, activators, modulators, phosphatases, kinases and other components. However, there is one central, critical molecule to this pathway, β-catenin. While there are at least 3 receptors, LRP 4, 5 and 6, and over twenty activators known as the wnts, and several inhibitors such as sclerostin, dickkopf and secreted frizzled-related protein, these all target β-catenin. These regulators/modulators function to target β-catenin either to the proteasome for degradation or to the nucleus to regulate gene expression. Therefore, the interaction of β-catenin with different factors and Wnt/β-catenin signaling pathway will be the subject of this review with a focus on how this pathway relates to and functions in the formation and maintenance of bone and teeth based on mainly basic and pre-clinical research. Also in this review, the role of this pathway in osteocytes, bone cells embedded in the mineralized matrix, is covered in depth. This pathway is not only important in mineralized tissue growth and development, but for modulation of the skeleton in response to loading and unloading and the viability and health of the adult and aging skeleton. PMID:27210503
Effect of AMPK signal pathway on pathogenesis of abdominal aortic aneurysms

PubMed Central

Yang, Le; Shen, Lin; Gao, Peixian; Li, Gang; He, Yuxiang; Wang, Maohua; Zhou, Hua; Yuan, Hai; Jin, Xing; Wu, Xuejun

2017-01-01

Background and aims Determine the effect of AMPK activation and inhibition on the development of AAA (abdominal aortic aneurysm). Methods AAA was induced in ApoE−/− mice by Ang II (Angiotensin II)-infusion. AICAR (5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside) was used as AMPK activator and Compound C was used as AMPK inhibitor. We further investigate the effect of metformin, a widely used anti-diabetic drug which could activate AMPK signal pathway, on the pathogenesis of aneurysm. Results Phospho-AMPK level was significantly decreased in AAA tissue compared with control aortas. AICAR significantly reduced the incidence, severity and mortality of aneurysm in the Ang II-infusion model. AICAR also alleviated macrophage infiltration and neovascularity in Ang II infusion model at day 28. The expression of pro-inflammatory factors, angiogenic factors and the activity of MMPs were also alleviated by AICAR during AAA induction. On the other hand, Compound C treatment did not exert obvious protective effect. AMPK activation may inhibit the activation of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription-3 (STAT-3) during AAA induction. Administration of metformin also activated AMPK signal pathway and retarded AAA progression in Ang II infusion model. Conclusions Activation of AMPK signaling pathway may inhibit the Ang II-induced AAA in mice. Metformin may be a promising approach to the treatment of AAA. PMID:29190959
Fatty acid-amino acid conjugates are essential for systemic activation of salicylic acid-induced protein kinase and accumulation of jasmonic acid in Nicotiana attenuata.

PubMed

Hettenhausen, Christian; Heinrich, Maria; Baldwin, Ian T; Wu, Jianqiang

2014-11-28

Herbivory induces the activation of mitogen-activated protein kinases (MAPKs), the accumulation of jasmonates and defensive metabolites in damaged leaves and in distal undamaged leaves. Previous studies mainly focused on individual responses and a limited number of systemic leaves, and more research is needed for a better understanding of how different plant parts respond to herbivory. In the wild tobacco Nicotiana attenuata, FACs (fatty acid-amino acid conjugates) in Manduca sexta oral secretions (OS) are the major elicitors that induce herbivory-specific signaling but their role in systemic signaling is largely unknown. Here, we show that simulated herbivory (adding M. sexta OS to fresh wounds) dramatically increased SIPK (salicylic acid-induced protein kinase) activity and jasmonic acid (JA) levels in damaged leaves and in certain (but not all) undamaged systemic leaves, whereas wounding alone had no detectable systemic effects; importantly, FACs and wounding are both required for activating these systemic responses. In contrast to the activation of SIPK and elevation of JA in specific systemic leaves, increases in the activity of an important anti-herbivore defense, trypsin proteinase inhibitor (TPI), were observed in all systemic leaves after simulated herbivory, suggesting that systemic TPI induction does not require SIPK activation and JA increases. Leaf ablation experiments demonstrated that within 10 minutes after simulated herbivory, a signal (or signals) was produced and transported out of the treated leaves, and subsequently activated systemic responses. Our results reveal that N. attenuata specifically recognizes herbivore-derived FACs in damaged leaves and rapidly send out a long-distance signal to phylotactically connected leaves to activate MAPK and JA signaling, and we propose that FACs that penetrated into wounds rapidly induce the production of another long-distance signal(s) which travels to all systemic leaves and activates TPI defense.
A nodal signaling pathway regulates the laterality of neuroanatomical asymmetries in the zebrafish forebrain.

PubMed

Concha, M L; Burdine, R D; Russell, C; Schier, A F; Wilson, S W

2000-11-01

Animals show behavioral asymmetries that are mediated by differences between the left and right sides of the brain. We report that the laterality of asymmetric development of the diencephalic habenular nuclei and the photoreceptive pineal complex is regulated by the Nodal signaling pathway and by midline tissue. Analysis of zebrafish embryos with compromised Nodal signaling reveals an early role for this pathway in the repression of asymmetrically expressed genes in the diencephalon. Later signaling mediated by the EGF-CFC protein One-eyed pinhead and the forkhead transcription factor Schmalspur is required to overcome this repression. When expression of Nodal pathway genes is either absent or symmetrical, neuroanatomical asymmetries are still established but are randomized. This indicates that Nodal signaling is not required for asymmetric development per se but is essential to determine the laterality of the asymmetry.
Macrophages produce IL-33 by activating MAPK signaling pathway during RSV infection.

PubMed

Qi, Feifei; Bai, Song; Wang, Dandan; Xu, Lei; Hu, Haiyan; Zeng, Sheng; Chai, Ruonan; Liu, Beixing

2017-07-01

It has been reported that RSV infection can enhance IL-33 production in lung macrophages. However, little is known about specific signaling pathways for activation of macrophages during RSV infection. In the present study, by using real-time RT-PCR as well as western blot assay, it became clear that RSV infection can enhance not only the expression of mRNAs for MAPK molecules (including p38, JNK1/2, and ERK1/2), but also the levels of MAPK proteins in lung macrophages as well as RAW264.7 cells. Furthermore, infection with RSV resulted in an increased level of phosphorylated MAPK proteins in RAW264.7 cells, suggesting that MAPK signaling pathway may participate in the process of RSV-induced IL-33 secretion by macrophages. In fact, the elevated production of IL-33 in RAW264.7 was attenuated significantly by pretreatment of the cells with special MAPK inhibitor before RSV infection, further confirming the function of MAPKs pathway in RSV-induced IL-33 production in macrophages. In contrast, the expression of NF-κB mRNA as well as the production of NF-κB protein in lung macrophages and RAW264.7 cells was not enhanced markedly after RSV infection. Moreover, RSV infection failed to induce the phosphorylation of NF-κB in RAW264.7 cells, suggesting that NF-κB signaling pathway may be not involved in RSV-induced IL-33 production in macrophages. Conclusion, these results indicate that RSV-induced production of IL-33 in macrophages is dependent on the activation of MAPK signaling pathway. Copyright © 2017 Elsevier Ltd. All rights reserved.
Jasmonic and salicylic acid response in the fern Azolla filiculoides and its cyanobiont.

PubMed

de Vries, Sophie; de Vries, Jan; Teschke, Hendrik; von Dahlen, Janina K; Rose, Laura E; Gould, Sven B

2018-01-03

Plants sense and respond to microbes utilizing a multilayered signalling cascade. In seed plants, the phytohormones jasmonic and salicylic acid (JA and SA) are key denominators of how plants respond to certain microbes. Their interplay is especially well-known for tipping the scales in plants' strategies of dealing with phytopathogens. In non-angiosperm lineages, the interplay is less well understood, but current data indicate that it is intertwined to a lesser extent and the canonical JA/SA antagonism appears to be absent. Here, we used the water fern Azolla filiculoides to gain insights into the fern's JA/SA signalling and the molecular communication with its unique nitrogen fixing cyanobiont Nostoc azollae, which the fern inherits both during sexual and vegetative reproduction. By mining large-scale sequencing data, we demonstrate that Azolla has most of the genetic repertoire to produce and sense JA and SA. Using qRT-PCR on the identified biosynthesis and signalling marker genes, we show that Azolla is responsive to exogenously applied SA. Furthermore, exogenous SA application influenced the abundance and gene expression of Azolla's cyanobiont. Our data provide a framework for JA/SA signalling in ferns and suggest that SA might be involved in Azolla's communication with its vertically inherited cyanobiont. © 2018 John Wiley & Sons Ltd.
Maternal Chromium Restriction Leads to Glucose Metabolism Imbalance in Mice Offspring through Insulin Signaling and Wnt Signaling Pathways

PubMed Central

Zhang, Qian; Sun, Xiaofang; Xiao, Xinhua; Zheng, Jia; Li, Ming; Yu, Miao; Ping, Fan; Wang, Zhixin; Qi, Cuijuan; Wang, Tong; Wang, Xiaojing

2016-01-01

An adverse intrauterine environment, induced by a chromium-restricted diet, is a potential cause of metabolic disease in adult life. Up to now, the relative mechanism has not been clear. C57BL female mice were time-mated and fed either a control diet (CD), or a chromium-restricted diet (CR) throughout pregnancy and the lactation period. After weaning, some offspring continued the diet diagram (CD-CD or CR-CR), while other offspring were transferred to another diet diagram (CD-CR or CR-CD). At 32 weeks of age, glucose metabolism parameters were measured, and the liver from CR-CD group and CD-CD group was analyzed using a gene array. Quantitative real-time polymerase chain reaction (qPCR) and Western blot were used to verify the result of the gene array. A maternal chromium-restricted diet resulted in obesity, hyperglycemia, hyperinsulinemia, increased area under the curve (AUC) of glucose in oral glucose tolerance testing and homeostasis model assessment of insulin resistance (HOMA-IR). There were 463 genes that differed significantly (>1.5-fold change, p < 0.05) between CR-CD offspring (264 up-regulated genes, 199 down-regulated genes) and control offspring. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) analysis revealed that the insulin signaling pathway and Wnt signaling pathway were in the center of the gene network. Our study provides the first evidence that maternal chromium deficiency influences glucose metabolism in pups through the regulation of insulin signaling and Wnt signaling pathways. PMID:27782077
Neurotrophic factors switch between two signaling pathways that trigger axonal growth.

PubMed

Paveliev, Mikhail; Lume, Maria; Velthut, Agne; Phillips, Matthew; Arumäe, Urmas; Saarma, Mart

2007-08-01

Integration of multiple inputs from the extracellular environment, such as extracellular matrix molecules and growth factors, is a crucial process for cell function and information processing in multicellular organisms. Here we demonstrate that co-stimulation of dorsal root ganglion neurons with neurotrophic factors (NTFs) - glial-cell-line-derived neurotrophic factor, neurturin or nerve growth factor - and laminin leads to axonal growth that requires activation of Src family kinases (SFKs). A different, SFK-independent signaling pathway evokes axonal growth on laminin in the absence of the NTFs. By contrast, axonal branching is regulated by SFKs both in the presence and in the absence of NGF. We propose and experimentally verify a Boolean model of the signaling network triggered by NTFs and laminin. Our results demonstrate that NTFs provide an environmental cue that triggers a switch between separate pathways in the cell signaling network.

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