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 anchoring proteins; b2

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

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 control receptor phosphorylation and synaptic plasticity. However, AKAP79/150 may also ...

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- ledge and Scott, 1999). A substantial number of different AKAP proteins have been

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 proteins (AKAPs) and exchange protein activated by c

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, A-kinase anchoring protein

-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 procedure using radiolabeled

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

,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 (AKAP)25,70 , which also binds PKC. Activation of ...

-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 KSR-1/AKAP- Lbc signaling

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 anchoring proteins (AKAPs). AKAPs

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 illustrates the essential features of AKAPs. Each

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 (AKAP); cAMP; Neuron; Synaptic plasticity; Learning

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

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 anchoring

) 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

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 dissemination of information from one ...

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, well-studied scaffolding ...

, 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 -O-dibutyryl cAMP; DMNB

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 different combinations of ...

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 forms a macromolecular ...

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 proteins

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 proteins: A-kinase anchoring ...

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

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 cells, AKAP79

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

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

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 proteins: A-kinase anchoring ...

... 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- ... ...

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 spermatozoa differ in structural organization from those of eutherian ...

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, well-studied scaffolding ...

In nature prion diseases are usually transmitted by extracerebral prion infection, but clinical disease results only after invasion of the central nervous system (CNS). Prion protein (PrP), a host-encoded glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein, is necessary for prion infection and disease. Here, we investigated the role 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 protein kinase A and components ...

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 assemblies. Especially for G-protein-coupled receptors, the AKAPs provide ...

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, which we termed trans-activator of ...

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, which we termed trans-activator of ...

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 regulatory subunit of PKA. The model was used to ...

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 type I PKA from ...

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 activation and may prove a feasible approach ...

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 activity at the leading ...

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 AKAP 18 gamma mRNA expressions while ...

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 anchoring proteins ...