MINIREVIEW Organizing signal transduction through A-kinase anchoring proteins (AKAPs) Jeremy S distinction between these two isoenzymes is their Keywords AKAP; cAMP; enzyme complexes; signal transduction signaling complexes are highlighted in this minireview. Abbreviations AKAP, A-kinase ...
E-print Network
E2; PKA, cAMP-dependent protein kinase; AKAP, A-kinase anchoring protein; PKC, protein kinase C; AR activity of PKA via A-kinase anchoring proteins (AKAPs) so that the kinase preferentially phosphorylates specific substrates (Col- ...
of proteins known as A-kinase- anchoring proteins (AKAPs). AKAPs provide a framework for the coordination with appropriate substrates. AKAPs also bring together signal transduction and signal termination molecules in a convergence of signaling pathways. Indeed, the dynamic assembly of these AKAP complexes represents a paradigm
of PKA signaling through AKAPs 5. A-kinase anchoring protein 150 6. Muscle AKAP 7. Role of AKAPs in learning and memory 8. Tools for AKAP research 9. Exchange protein directly activated by cAMP 10. Aim discovered, cAMP signaling avenues, A-kinase anchoring ...
AKAP9 (A-kinase anchor protein), also known as yotiao or A0009, forms a macromolecular complex with different ion channels and recruits key enzymes such as cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) and protein phosphatase 1
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protein kinase A (PKA), and A-kinase anchoring proteins (AKAPs), known to interact with PKA and c1 interacts with PDE4D3 within a cAMP-responsive multiprotein complex, which contains mAKAP, PKA of the A-kinase anchoring family. GPCRs, G protein-coupled receptors; AKAP, ...
-kinase-anchoring protein, AKAP79/150, co-precipitates with the 2-AR in cell and tissue extracts, nucleating a signaling and to facilitate downstream activation of the MAP kinase pathway. This defines a role for AKAP79 for co-purifying A-kinase anchoring proteins (AKAPs) by an in vitro overlay ...
in cellular responses. AKAPs The first RII-binding proteins were identified as contaminating proteins, which-binding proteins were renamed A-kinase anchoring proteins or AKAPs to account for their proposed PKA- targeting function (26). A model is presented in Fig. 1, which ...
,5)P2 AKAP PKC CaMI CaMII P P Quantitative aspects of PtdIns(4,5)P2 depletion PtdIns(4,5)P2 comprises)-induced enhancement of Kv7 currents57 . AKAP, A-kinase anchoring protein; PtdIns(4,5)P2 , phosphatidylinositol-4 channel proteins bind A-kinase anchoring ...
Protein scaffold complexes are a key mechanism by which a common signaling pathway can serve many different functions. Sequestering a signaling enzyme to a specific subcellular environment not only ensures that the enzyme is near its relevant targets, but also segregates this activity to prevent indiscriminate phosphorylation of other substrates. One family of diverse, ...
PubMed Central
-signal regulated kinase; MAPK, mitogen-activated protein kinase; AKAP, A-kinase anchoring protein; PKA, c We recently discovered that KSR-1 and the A-Kinase Anchoring Protein (AKAP)- Lbc form the core lie in the actions of PKA and its substrates within the confines of the ...
by Robin Leatherbarrow A-kinase anchoring proteins (AKAPs) localize cyclic AMP-dependent protein kinase. A computational model was created to identify AKAPs that bind to the docking/dimerization domain of the RII alpha/D) domain, and the D/D domain provides an interaction surface for A-kinase ...
of synaptic plasticity through AKAP signaling complexes Andrea L. Bauman, April S. Goehring, John D. Scott � how the compartmentalization of PKA through its association with A-Kinase Anchoring Proteins (AKAPsAMP-dependent Protein Kinase (PKA); A-Kinase Anchoring Protein ...
of protein kinase (PK)C to the surface membrane by the kinase anchoring protein AKAP150 (the rodent ortholog of human AKAP79) increases the probability of persistent Cav1.2 channel activity,9 the mechanisms by which eliminated by the application of the Non-standard Abbreviations and Acronyms AKAP150 A-kinase ...
) through its associa- tion with A-kinase anchoring proteins (AKAPs). cAMP-dependent signaling mechanisms AKAPs exist to restrict the diffusion of the kinase and place the enzyme close to certain substrates). This review concentrates on the role of AKAPs as molecular mediators of PKA signaling speci- ficity
, AKAPs) (1�3). Local- ization recruits the PKA holoenzyme close to its substrate effector proteins by peptides that antagonize PKA�AKAP interactions often disables cAMP- dependent signaling (4, 5), emphasizing: AKAP, A-kinase anchor protein; AKAR, A-kinase activity reporter; Bt2cAMP, N6,2 ...
This Teaching Resource provides lecture notes and slides for a class covering the roles of scaffold proteins in signal transduction and is part of the course "Cell Signaling Systems: A Course for Graduate Students." The lecture includes an overview of scaffold proteins in signal integration and focuses on the following scaffold ...
PubMed
The pleiotropic cyclic nucleotide cAMP is the primary second messenger responsible for autonomic regulation of cardiac inotropy, chronotropy, and lusitropy. Under conditions of prolonged catecholaminergic stimulation, cAMP also contributes to the induction of both cardiac myocyte hypertrophy and apoptosis. The formation of localized, multi-protein complexes that contain ...
A-Kinase Anchoring Proteins (AKAPs) orchestrate and synchronize cellular events by tethering the cAMP-dependent protein kinase (PKA) and other signaling enzymes to organelles and membranes. The control of kinases and phosphatases that are held in proximity to activators, effectors, and substrates favors the rapid ...
A-kinase anchoring proteins (AKAPs) create compartmentalized environment inside the cell to bring various signaling molecules to their targets. In the heart, a slowly activating potassium channel (IKs) important for cardiac repolarization is tightly regulated by the sympathetic nervous system in an AKAP-dependent manner. IKs channel ...
of these proteins to caveolae and/or A-kinase anchoring #12;General discussion and summary 205 protein (AKAP) complexes. For example, co-localization of PKA and Epac to distinct AKAPs has been associated with opposing biological effects of the two cAMP effectors in cardiomyocytes and neurons [22, 23]. In neuronal ...
Chapter 3 Both exposure to a novel context and associative learning induce an upregulation of AKAP Abstract A-kinase anchoring protein 150 (AKAP150) is a multi-enzyme signaling complex that coordinates the action of PKA, PKC, and PP2B at neuronal membranes and synapses. We measured levels of AKAP150 protein
... ml; Sigma). Secondary antibodies were anti-rabbit Alexa Fluor 488 (4 μg/ml; Molecular Probes, Eugene, OR), anti-mouse Alexa Fluor 633 (4 μg/ml; Molecular Probes), or Cy5- ... ...
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of the enzyme near its substrates through association withA-kinase anchoring proteins (AKAPs). Here, we provide evidence for interactions between AKAP79/150 and ACV and ACVI. PKA anchoring facili- tates the preferential) (Bos, 2003; Dodge-Kafka et al., 2005; Zaccolo and Pozzan, 2002). AKAPs tether these effector ...
A-kinase anchor protein 4 (AKAP4) is an X-linked member of the AKAP family of scaffold proteins that anchor cAMP-dependent protein kinases and play an essential role in fibrous sheath assembly during spermatogenesis and flagellar function in spermatozoa. Marsupial ...
of the regu- latorysubunit (RII) withA-KinaseAnchorProteins (AKAPs).In previous studies (Scott,J. D., Stofko lacking resi- dues 1-5) was unable to bind AKAPs but retained the ability to dimerize. RIIrv 13AJ5A (a mutant where iso- leucines3 and 5were replaced with alanine) was unable to binda variety ofAKAPs
... of the ASP gene, but similar analyses of busulfan-treated germ cell-deficient mice failed to detect ... injected (i.p.) with 40 mg/kg of busulfan (Sigma, St. Louis, MO) as previously described [10, ... ...
and spatial memory consolidation in the hippocampus99�101 . Furthermore,theA-kinase anchoring proteins (AKAPs that competes with the binding of PKA to AKAP into the lateral amygdala 1 h before FEAR CONDITIONING impaired after training had no effect. The specific contribution of AKAP and PKA with phosphorylation of GluR1
-gestuurde signaaltransductie be�nvloed worden door binding van deze eiwitten aan zogenaamde A-kinase anchoring proteins (AKAP). Epac1, Rap1 en - in mindere mate - PKA, AKAP79 en Epac2 bevinden zich voor een deel in caveolaire belangrijke rol (hoofdstuk 4), mogelijk via de vorming van een complex met AKAP79 (hoofdstuk 6). Tevens werd
in the cartilage nuclear fraction. Furthermore, a novel �150-kDa A-kinase anchoring protein (AKAP), which binds reduction in the amounts of both nuclear RII and nAKAP150. These observations indicate that type II PKA to depend on the the activity of the developmentally regulated nAKAP150. 1996 Academic Press, Inc
Chapter 5 Detailed analysis of mAKAP expression in the brain of young and old mice Anghelus In preparation #12;Chapter 5 Abstract A-kinase anchoring proteins (AKAPs) form large macromolecular signaling and thus provide high specificity to PKA signaling. One important member of this family is mAKAP. Although
AKAPs (A-kinase anchoring proteins) are members of a diverse family of scaffold proteins that minimally possess a characteristic binding domain for the RI/RII regulatory subunit of protein kinase A and play critical roles in establishing spatial constraints for multivalent signalling ...
A-kinase anchoring proteins (AKAPs) localize cyclic AMP-dependent protein kinase (PKA) to specific regions in the cell and place PKA in proximity to its phosphorylation targets. A computational model was created to identify AKAPs that bind to the docking/dimerization domain of the RII alpha isoform of the ...
The formation of multiprotein complexes is a repeated theme in biology ranging from the regulation of the extracellular signal-regulated kinase and cAMP signaling pathways to the formation of postsynaptic density complexes or tight junctions. A-kinase anchoring proteins (AKAPs) are well known for their ability to scaffold ...
Type I protein kinase A (PKA) is targeted to the TCR-proximal signaling machinery by the A-kinase anchoring protein ezrin and negatively regulates T cell immune function through activation of the C-terminal Src kinase. RI anchoring disruptor (RIAD) is a high-affinity competitor peptide that specifically displaces ...
We have reported previously the design of a RIAD (RI-anchoring disruptor) peptide that specifically displaces PKA (protein kinase A) type I from the AKAP (A-kinase-anchoring protein) ezrin, which is present in the immunological synapse of T-cells. This increases immune reactivity by reducing the threshold for ...
of the expressed channels was observed afterA-kinase anchoring protein called AKAP79. In trans- increases in cAMP (Yoshida et al., 1992; Yatani et al.,fected cells expressing a mutant AKAP79 that is un- 1995). Thus have shown that the 1Ction of an AKAP with PKA was required for -adrener- subunit is a substrate
The muscle A-kinase anchoring protein (mAKAP) teth- ers cAMP-dependent enzymes to perinuclear mem- branes of cardiomyocytes. We now demonstrate that two alternatively spliced forms of mAKAP are ex- pressed: mAKAPa and m enzymes (Pawson and Scott, 1997). AKAPs are such scaffolds, defined by their ability to an- chor the PKA
Localization of protein kinase A (PKA) via A-kinase-anchoring proteins (AKAPs) is important for cAMP responsiveness in many cellular systems, and evidence suggests that AKAPs play an important role in cardiac signaling. To test the importance of AKAP-mediated targeting of PKA on cardiac function, we designed a cell-permeable peptide, ...
Cyclic AMP (cAMP)-dependent protein kinase (PKA) is a signalling molecule involved in the regulation of many physiological functions including those of cilia and flagella. PKA localizes to specific cellular structures and organelles by binding to AKAP (A-kinase anchoring protein) molecules via interaction with the ...
A-kinase anchoring proteins (AKAPs) include a family of scaffolding proteins that target protein kinase A (PKA) and other signaling proteins to cellular compartments and thereby confine the activities of the associated proteins to distinct regions ...
A-kinase anchoring proteins (AKAPs) are thought to be passive members of protein complexes that coordinate the association of cAMP-dependent protein kinase A (PKA) with cellular substrates to facilitate targeted PKA protein phosphorylation. IKs, the ...
Protein kinase A (PKA) has been suggested to be spatially regulated in migrating cells due to its ability to control signaling events that are critical for polarized actin cytoskeletal dynamics. Here, using the fluorescence resonance energy transfer-based A-kinase activity reporter (AKAR1), we find that PKA activity gradients form with the strongest ...
A-kinase Anchoring Proteins (AKAPs) define an expanding group of scaffold proteins that display a signature binding site for the RI/RII subunit of protein kinase A. AKAP5 and AKAP12 are multivalent (with respect to protein kinases and phosphatases) and display the ability ...
A-kinase anchoring proteins (AKAPs) are known to compartmentalise protein kinase(s) to discrete cellular locations. Here we show that silencing of AKAP 18 alpha or gamma expression results in decreased or increased glucose-stimulated insulin secretion in INS-1E cells. Glucose stimulates AKAP 18 alpha and inhibits ...
Certain phosphorylation events are tightly controlled by scaffolding proteins such as A-kinase anchoring protein (AKAP). On nociceptive terminals, phosphorylation of transient receptor potential channel type 1 (TRPV1) results in the sensitization to many different stimuli, contributing to the development of hyperalgesia. In this study, ...
Certain phosphorylation events are tightly controlled by scaffolding proteins such as A-Kinase Anchoring Protein (AKAP). On nociceptive terminals, phosphorylation of transient receptor potential channel type 1 (TRPV1) results in the sensitization to many different stimuli, contributing to the development of hyperalgesia. In this study, ...
Cyclic adenosine 3?, 5? monophosphate (cAMP) is a ubiquitous mediator of intracellular signalling events. It principally acts through stimulation of cAMP-dependent protein kinases (PKA)1, 2 but also activates certain ion-channels and guanine nucleotide exchange factors (Epacs)3. Metabolism of cAMP is catalyzed by phosphodiesterases (PDEs)4, 5. A cAMP-responsive signalling ...
A-kinase anchoring protein 79 (AKAP79) is a human anchoring protein that organizes cAMP-dependent protein kinase (PKA), Ca(2+)/calmodulin (CaM)-dependent protein phosphatase (PP2B), and protein kinase C (PKC) for phosphoregulation ...
A-kinase anchoring protein 79 (AKAP79) is a human anchoring protein that organizes cAMP-dependent protein kinase (PKA), Ca2+/calmodulin (CaM)-dependent protein phosphatase (PP2B), and protein kinase C (PKC) ...
Polycystic kidney disease (PKD) is a genetic disorder that is characterized by cyst formation in kidney tubules. PKD arises from abnormalities of the primary cilium, a sensory organelle located on the cell surface. Here, we show that the primary cilium of renal epithelial cells contains a protein complex comprising adenylyl cyclase 5/6 (AC5/6), A-kinase ...
BackgroundDendritic cells (DC) are the most potent antigen presenting cells (APC) of the immune system. Prostaglandin E2, cyclic AMP, and protein kinase A (PKA) have all been shown to regulate DC maturation and activity. In other cells, the ability of these molecules to convey their signals has been shown to be dependent on A-kinase ...
The second messenger cyclic adenosine monophosphate (cAMP), which is produced by adenylyl cyclases following stimulation of G-protein-coupled receptors, exerts its effect mainly through the cAMP-dependent serine/threonine protein kinase A (PKA). Due to the ubiquitous nature of the cAMP/PKA system, PKA signaling pathways underlie strict spatial and temporal ...
The myeloid translocation gene (MTG) homologue Nervy associates with PlexinA on the plasma membrane, where it functions as an A-kinase anchoring protein (AKAP) to modulate plexin-mediated semaphorin signaling in Drosophila. Mammalian MTG16b is an AKAP found in immune cells where plexin-mediated semaphorin signaling regulates immune responses. This study ...
Muscle A-kinase anchoring protein (mAKAP) is a scaffold protein found principally at the nuclear envelope of striated myocytes. mAKAP maintains a complex consisting of multiple signal transduction molecules including the cAMP-dependent protein kinase A, the ryanodine receptor calcium release ...
Energy Citations Database
A-kinase anchoring proteins (AKAPs) bind to protein kinase A (PKA) via an amphipathic helix domain that interacts with a dimerization/docking domain on the regulatory (R) subunit of PKA. Four other mammalian proteins (ROPN1, ASP, SP17, and CABYR) also contain a highly conserved RII ...
Activation of protein kinases and phosphatases at the plasma membrane often initiates agonist-dependent signalling events. In sensory neurons, AKAP150 (A-kinase-anchoring protein 150) orientates PKA (protein kinase A), PKC (protein kinase C) and the ...
Collagen deposition by fibroblasts contributes to scarring in fibrotic diseases. Activation of protein kinase A (PKA) by cAMP represents a pivotal brake on fibroblast activation, and the lipid mediator prostaglandin E(2) (PGE(2)) exerts its well known anti-fibrotic actions through cAMP signaling. However, fibrotic fibroblasts from the lungs of patients with idiopathic ...
A-kinase anchoring protein (AKAP) 79/150 is a scaffold protein found in dendritic spines that recruits the cAMP-dependent protein kinase (PKA) and protein phosphatase 2B-calcineurin (CaN) to membrane-associated guanylate kinase (MAGUK)-linked AMPA receptors (AMPARs) to ...
subunits, including PNUTS and AKAP220, interact with PP1 through sites outwith their RVXF-like motifs18 the interac- tion of the R subunits with AKAPs (A-kinase-anchoring pro- teins)41�43 . High-affinity interaction with the type 1 or type II PKA isozymes is mediated by an amphipathic helix on the AKAP, which
Mitochondria are highly specialized organelles and major players in fundamental aspects of cell physiology. In yeast, energy metabolism and coupling of mitochondrial activity to growth and survival is controlled by the protein kinase A pathway. In higher eukaryotes, modulation of the so-called A-kinase anchor ...
Post-translational modifications on various receptor proteins have significant effects on receptor activation. For the Transient Receptor Potential family V type 1 (TRPV1) receptor, phosphorylation of certain serine/threonine amino acid residues sensitizes the receptor to activation by capsaicin and heat. Although Protein Kinase C (PKC) phosphorylates ...
Kv4.2, as the primary ?�subunit of rapidly inactivating, A-type voltage-gated K+ (Kv) channels expressed in hippocampal CA1 pyramidal dendrites, plays a critical role in regulating their excitability. Activity-dependent trafficking of Kv4.2 relies on C-terminal protein kinase A (PKA) phosphorylation. A-kinase ...
The mitogen-activated protein kinases (MAPKs) pathways are highly organized signaling systems that transduce extracellular signals into a variety of intracellular responses. In this context, it is currently poorly understood how kinases constituting these signaling cascades are assembled and activated in response to receptor stimulation to generate specific cellular responses. ...
A-kinase anchoring proteins (AKAPs) regulate cyclic AMP-dependent protein kinase (PKA) signaling in space and time. Dual-specific AKAP 2 (D-AKAP2) binds to the dimerization/docking (D/D) domain of both RI and RII regulatory subunits of PKA with high affinity. Here we have determined the structures of the RIalpha ...
A-kinase anchoring proteins (AKAPs) regulate cyclic AMP-dependent protein kinase (PKA) signaling in space and time. Dual-specific AKAP 2 (D-AKAP2) binds to the dimerization/docking (D/D) domain of both RI and RII regulatory subunits of PKA with high affinity. Here we have determined the structures of the RI{alpha} ...
Previously, we reported that lysophosphatidic acid (LPA)-induced adenosine 3',5'-cyclic monophosphate (cAMP) production by human diploid fibroblasts depends on the age of the fibroblasts. In this study, we examined the role of A-kinase anchoring proteins (AKAP) in the regulation of LPA-stimulated cAMP production in senescent fibroblasts. We found that ...
Positioned at the C-terminus of many eukaryotic proteins, the glycosylphosphatidylinositol (GPI) anchor is a posttranslational modification that anchors the modified protein in the outer leaflet of the cell membrane. The GPI anchor is a complex structure comprising a phosphoethanolamine linker, ...
Nitric oxide (NO) enhances human sperm motility and capacitation associated with increased protein phosphorylation. NO activates soluble guanylyl cyclase, but can also modify protein function covalently via S-nitrosylation of cysteine. Remarkably, this mechanism remains unexplored in sperm although they depend on post-translational ...
A mitosis-specific Aurora-A kinase has been implicated in microtubule organization and spindle assembly in diverse organisms. However, exactly how Aurora-A controls the microtubule nucleation onto centrosomes is unknown. Here, we show that Aurora-A specifically binds to the COOH-terminal domain of a Drosophila centrosomal protein, ...
... kDa protein with the plasma membrane via a glycolipid (GPI) anchor was predicted by both the �PSORTII� ... solutions Due to the hydrophobic nature of their glycolipid anchors, GPI-linked proteins partiti...
Efficient and specific phosphorylation of PKA substrates, elicited in response to ?-adrenergic stimulation, require spatially confined pools of PKA anchored in proximity of its substrates. PKA-dependent phosphorylation of cardiac sarcomeric proteins has been the subject of intense investigations. Yet, the identity, composition, and function of PKA ...
Adipose LPL (lipoprotein lipase) plays an important role in regulating plasma triacylglycerols and lipid metabolism. We have previously demonstrated that PKCalpha (protein kinase Calpha) depletion inhibits LPL translation in 3T3-F442A adipocytes. Using in vitro translation experiments, the minimum essential region on the 3'UTR (3'-untranslated region) of LPL mRNA required for ...
The mechanisms by which a promiscuous protein can strongly interact with several different proteins using the same binding interface are not completely understood. An example is protein kinase A (PKA), which uses a single face on its docking/dimerization domain to interact with multiple A-kinase ...
A-kinase anchoring proteins (AKAPs) tether cyclic AMP-dependent protein kinases and thereby localize phosphorylation of target proteins and initiation of signal-transduction processes triggered by cyclic AMP. AKAPs can also be scaffolds for kinases and phosphatases and form macromolecular ...
To identify candidate proteins in the nucleus accumbens (NAc) as potential pharmacotherapeutic targets for treating cocaine addition, an 8-plex iTRAQ (isobaric tag for relative and absolute quantitation) proteomic screen was performed using NAc tissue obtained from rats trained to self-administer cocaine followed by extinction training. Compared with yoked-saline controls, 42 ...
Decay accelerating factor (DAF) belongs to a novel group of membrane proteins anchored to the cell surface by a glycophospholipid membrane anchor that is covalently attached to the carboxyl terminus of the protein. The last 37 amino acids of membrane DAF, when fused to the carboxyl terminus of a secreted ...
WAVE proteins are members of the Wiskott�Aldrich syndrome protein (WASP) family of scaffolding proteins that coordinate actin reorganization by coupling Rho-related small molecular weight GTPases to the mobilization of the Arp2/3 complex. We identified WAVE-1 in a screen for rat brain A�kinase-anchoring ...
Glycosylphosphatidylinositol (GPI)-anchored proteins are secretory proteins that are attached to the cell surface of eukaryotic cells by a glycolipid moiety. Once GPI anchoring has occurred in the lumen of the endoplasmic reticulum (ER), the structure of the lipid part on the GPI anchor ...
BackgroundCardiac contractility is regulated by dynamic phosphorylation of sarcomeric proteins by kinases such as cAMP-activated protein kinase A (PKA). Efficient phosphorylation requires that PKA be anchored close to its targets by A-kinase anchoring proteins (AKAPs). Cardiac Myosin Binding ...
The involvement of CK1 (casein kinase 1) delta in the regulation of multiple cellular processes implies a tight regulation of its activity on many different levels. At the protein level, reversible phosphorylation plays an important role in modulating the activity of CK1delta. In the present study, we show that PKA (cAMP-dependent protein kinase), Akt ...
The involvement of CK1 (casein kinase 1) ? in the regulation of multiple cellular processes implies a tight regulation of its activity on many different levels. At the protein level, reversible phosphorylation plays an important role in modulating the activity of CK1?. In the present study, we show that PKA (cAMP-dependent protein kinase), Akt ...
Like for all aurora-A kinases, the Xenopus pEg2 kinase level peaks in G(2)/M and is hardly detectable in G(1) cells, suggesting that the protein is degraded upon exit from mitosis as reported for the human aurora-A kinase. We identified for the first time a sequence RxxL in the C-terminal end ...
A-kinase anchoring proteins (AKAPs) tether protein kinase A (PKA) and other signaling proteins to defined intracellular sites, thereby establishing compartmentalized cAMP signaling. AKAP-PKA interactions play key roles in various cellular processes, including the regulation of cardiac myocyte ...
cAMP-dependent protein kinase A (PKA) is important in processes requiring localized cell protrusion, such as cell migration and axonal path finding. Here, we used a membrane-targeted PKA biosensor to reveal activation of PKA at the leading edge of migrating cells. Previous studies show that PKA activity promotes protrusion and efficient cell migration. In live migrating cells, ...
Numerous cAMP-elevating agents regulate events required for efficient migration of arterial vascular smooth muscle cells (VSMCs). Interestingly, when the impact of cAMP-elevating agents on individual migration-related events is studied, these agents have been shown to have distinct, and sometimes unexpected, effects. For example, although cAMP-elevating agents inhibit overall migration, they ...
The skeletal muscle L-type Ca2+ channel (CaV1.1), which is responsible for initiating muscle contraction, is regulated by phosphorylation by cAMP-dependent protein kinase (PKA) in a voltage-dependent manner that requires direct physical association between the channel and the kinase mediated through A-kinase anchoring ...
NASA Astrophysics Data System (ADS)
BackgroundA-kinase-anchoring proteins, AKAPs, constitute a family of scaffolds that play an essential role in catalyzing the spatial-temporal, dynamic interactions of protein kinase A, protein kinase C, tyrosine kinases, G-protein-coupled receptors and ion channels. We studied AKAP5 (AKAP79; MW ...
Targeting of Protein Kinase A by Muscle A Kinase-anchoring Protein (mAKAP) Regulates A anchoring proteins (AKAPs) tether cAMP-dependent protein kinase (PKA) to specific sub- cellular locations. The muscle AKAP, mAKAP, co-local- izes with the sarcoplasmic reticulum Ca2 ...
A-kinase (PKA) anchoring proteins (AKAPs) are essential for targeting type II PKA to specific locales in the cell to control function. In the present study, AKAP5 (formerly AKAP150) and AKAP6 were identified in mouse parotid acini by type II PKA regulatory subunit (RII) overlay assay and Western blot analysis of mouse parotid cellular ...
Sleep is important for brain function and cognitive performance. Sleep deprivation (SD) may affect subsequent learning capacity and ability to form new memories, particularly in the case of hippocampus-dependent tasks. In the present study we examined whether SD for 6 or 12 h during the normal resting phase prior to learning affects hippocampus-dependent working memory in mice. In addition, we ...
Here we reveal that the characterization of large-scale re-arrangements of signaling scaffolds induced by heart failure can serve as a novel concept to identify more specific therapeutic targets. In the mammalian heart, the cAMP pathway, with the cAMP-dependent protein kinase (PKA) in a central role, acts directly downstream of adrenergic receptors to mediate cardiac ...
Voltage-gated potassium (Kv) channels play important roles in regulating the excitability of myocytes and neurons. Kv4.2 is the primary ?-subunit of the channel that produces the A-type K+ current in CA1 pyramidal neurons of the hippocampus, which is critically involved in the regulation of dendritic excitability and plasticity. K+ channel-interacting ...
Preeclamptic women have enhanced blood pressure response to angiotensin II and extensive systemic vascular infiltration of neutrophils. Neutrophils release reactive oxygen species that might activate the RhoA kinase pathway to enhance vascular reactivity. We hypothesized that enhanced vascular reactivity in preeclampsia is attributed to neutrophil-mediated ...
-kinase anchoring protein AKAP220 Robynn V. Schillace and John D. Scott The cyclic AMP (cAMP)-dependent protein subunits with A-kinase anchoring proteins (AKAPs), whereas a diverse family of phosphatase-anchoring protein, AKAP220, binds PP1c with a ...
CAMP factor (protein B) is a pore-forming protein secreted by Streptococcus agalactiae. It causes lysis of sheep red blood cells when these have been sensitized with staphylococcal sphingomyelinase. We here show that CAMP factor binds to GPI-anchored proteins, and that this interaction involves the carbohydrate ...
Many eukaryotic proteins are tethered to the plasma membrane by glycosyl phosphatidylinositol (GPI) membrane anchors. This unit provides a general approach for detecting GPI-anchored proteins. First, the detergent-partitioning behavior of a protein of interest is examined for characteristics of ...
SummaryTail-anchored proteins are a distinct class of integral membrane proteins located in several eukaryotic organelles, where they perform a diverse range of functions. These proteins have in common the C-terminal location of their transmembrane anchor and the resulting post-translational ...
BackgroundAKAP12/Gravin (A kinase anchor protein 12) is one of the A-kinase scaffold proteins and a potential tumor suppressor gene in human primary cancers. Our recent study demonstrated the highly recurrent loss of AKAP12 in colorectal cancer and AKAP12 reexpression inhibited proliferation ...
A subset of AKAPs (A Kinase Anchoring Proteins) regulate signaling and cytoskeletal pathways through the spaciotemporal scaffolding of multiple protein kinases (PK), such as PKC and PKA, and associations with the plasma membrane and the actin-based cytoskeleton. SSeCKS/Gravin/Akap12 expression ...
Objective:Cyclic adenosine monophosphate/protein kinase A (PKA) is important in embryonic development. The human AKAP10 gene is polymorphic: 1936A>G results in changes to a PKA-binding domain and increased targeting to mitochondria. Previous studies found G1936 as 'deleterious' in adults, and this study investigates whether this holds true in preterm birth.Study ...
A-Kinase anchoring proteins (AKAPs) optimize the efficiency of cAMP signaling by clustering interacting partners. Recently, AKAP79 has been reported to directly bind to adenylyl cyclase type 8 (AC8) and regulate its responsiveness to store-operated Ca2+-entry (SOCE). Although AKAP79 is well-targeted to the PM via phospholipid ...
BackgroundThe transient receptor potential vanilloid type1 (TRPV1) is expressed in nociceptive sensory neurons and is sensitive to phosphorylation. A-Kinase Anchoring Protein 79/150 (AKAP150) mediates phosphorylation of TRPV1 by Protein Kinases A and C, modulating channel activity. However, few studies have focused ...
Modulation of phosphorylation states of ion channels is a critical step in the development of hyperalgesia during inflammation. Modulatory enhancement of channel activity may increase neuronal excitability and affect downstream targets such as gene transcription. The specificity required for such regulation of ion channels quickly occurs via targeting of protein kinases and ...
Glycosylphosphatidylinositol (GPI)-anchored proteins comprise a diverse class of membrane molecules. They protect cells from complement-mediated lysis, control cell to cell adhesion, activate T cells, and play a role in the etiology of slow viral diseases. Despite their functional diversity, GPI-anchored proteins ...
The post-translational integration of tail-anchored proteins at the endoplasmic reticulum represents a novel and distinct pathway for membrane protein synthesis. Studies of various precursors, exemplified by the synaptobrevins and cytochrome b5, indicate that multiple routes may facilitate their biosynthesis. There is clear evidence ...
Membrane-Anchoring Interactions of Bacteriophage Major Coat Proteins A.B. Meijer #12;#12;Membrane-Anchoring Interactions of Bacteriophage Major Coat Proteins A.B. Meijer #12;promotor: prof. dr. T.J. Schaafsma, hoogleraar Coat Proteins A.B. Meijer Proefschrift ter verkrijgingvan de graad van ...
Misfolding and subsequent aggregation of endogeneous proteins constitute essential steps in many human disorders, including Alzheimer and prion diseases. In most prion protein-folding studies, the posttranslational modifications, the lipid anchor in particular, were lacking. Here, we studied a fully posttranslationally modified ...
of Syne pro- teins in nuclear anchoring, we generated transgenic mice overex- pressing the conserved C in transgenic mice, demonstrating that localization and positioning of synaptic nuclei require Syne proteins. We aggregates are required for synaptic development and maintenance. Materials and Methods Transgenic Mice
A large number of eukaryotic proteins have been shown to be anchored to the cell membrane by glycosylphosphatidylinositol (GPI). This glycolipid anchor can serve as a substrate for anchor-specific phospholipases that convert the GPI-anchored membrane proteins into soluble ...
