Affinage

AKAP5

A-kinase anchor protein 5 · UniProt P24588

Length
427 aa
Mass
47.1 kDa
Annotated
2026-06-09
91 papers in source corpus 54 papers cited in narrative 54 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AKAP5 (AKAP79/150) is a multivalent membrane-targeted scaffold that simultaneously anchors the kinase PKA, the phosphatase calcineurin (PP2B), and PKC at distinct binding sites to coordinate compartmentalized phosphorylation/dephosphorylation cycles in neurons and other tissues (PMID:8599116). Systematic mutagenesis defined its modular architecture: a C-terminal RII (PKA)-binding helix (PMID:8509414), an internal calcineurin-anchoring site centered on a short IAIIIT/LxxIP linear motif (PMID:12354762, PMID:22343722, PMID:28967377), and an N-terminal region that both binds and inhibits the PKC catalytic core via a pseudosubstrate-like Arg39/Arg40 mechanism (PMID:10510312). The same N-terminal polybasic/hydrophobic regions target the scaffold to the membrane through PtdIns(4,5)P2 and acidic phospholipid binding (PMID:9545238) and through DHHC2-mediated palmitoylation of two N-terminal cysteines that direct it to lipid rafts and recycling endosomes (PMID:21771783, PMID:25589740); Ca2+/calmodulin and PKC activation release AKAP5 from membranes and from channel partners, and calmodulin competes directly with PKC for the N-terminal site (PMID:9202019, PMID:9545238, PMID:20147557). Native mass spectrometry and EM established that AKAP5 dimerizes to assemble a ~466 kDa quaternary complex in which Ca2+/CaM binding generates a second interface that activates anchored phosphatase, and that intrinsic disorder permits conformational flexibility in PP2B engagement (PMID:21464287, PMID:28967377). Through these modules AKAP5 docks PKA, calcineurin, PKC, adenylyl cyclases (AC2/5/6/8/9) and PP1 onto ion channels and receptors—CaV1.2, TRPV1, KCNQ2-5, Kir2.1, Kv4.2, KATP, Orai1/STIM, and β1/β2-adrenergic, muscarinic, P2Y and RXFP1 GPCRs—to bidirectionally control channel activity, trafficking and receptor recycling (PMID:17640527, PMID:18701070, PMID:20147557, PMID:21273417, PMID:33082339, PMID:33941685, PMID:20664520). In neurons this organization governs AMPA receptor phosphorylation and trafficking underlying LTP, LTD and homeostatic synaptic scaling (PMID:11943807, PMID:23649627, PMID:25451194, PMID:34612814), and couples local Ca2+ entry through L-type channels and Orai1 to calcineurin-dependent NFAT transcription, including feedback upregulation of KCNQ channels (PMID:17640527, PMID:23259949, PMID:31091162, PMID:33941685). In cardiac and arterial myocytes AKAP5 nucleates caveolin-3- and AC5-associated nanocomplexes that confer β-adrenergic and purinergic control of CaV1.2, calcium handling, and vasoconstriction, with knockout causing cardiac dilatation and dysfunction (PMID:20671242, PMID:25225170, PMID:33082339). AKAP5 also functions as a PKA-dependent regulatory node for GRK2 recruitment and β2AR desensitization (PMID:11278469) and acts directly as a PP1 inhibitory subunit (PMID:21561082).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1993 High

    Established the modular domain organization that makes AKAP5 a targeting scaffold, separating membrane/cytoskeletal anchoring from PKA tethering.

    Evidence Deletion and scanning mutagenesis with subcellular fractionation and RII binding assays in HEK293 cells

    PMID:8509414

    Open questions at the time
    • Did not address how the same protein engages calcineurin or PKC
    • Membrane targets of the N-terminal domains not yet identified
  2. 1996 High

    Defined the central concept that AKAP5 is a single scaffold binding three signaling enzymes (PKA, calcineurin, PKC) at distinct sites, enabling coordinated localization.

    Evidence Deletion analysis and binding studies with co-IP and immunofluorescence co-distribution in neurons

    PMID:8599116

    Open questions at the time
    • Whether the three enzymes occupy one complex simultaneously not directly shown
    • No functional readout of coordinated signaling
  3. 1997 High

    Showed Ca2+/calmodulin acts as a regulatory switch on the scaffold by competing with PKC for the N-terminal site and releasing active PKC.

    Evidence Calmodulin binding assays with KD measurement, co-IP, PKC activity assays in hippocampal neurons

    PMID:9202019

    Open questions at the time
    • Physiological trigger of CaM competition in vivo not established
  4. 1998 High

    Resolved how AKAP5 reaches the membrane and how PKC inhibition works, linking lipid binding and pseudosubstrate displacement to regulated targeting.

    Evidence GFP imaging of mutants, lipid-binding/fractionation assays, in vitro PKC binding and kinase assays with mutagenesis (combined across studies)

    PMID:10510312 PMID:9545238 PMID:9765270

    Open questions at the time
    • Relative in vivo contribution of lipid binding vs palmitoylation unresolved at this stage
    • Calcineurin inhibition mechanism only partially mapped
  5. 2002 High

    Demonstrated that the scaffold assembles a true ternary kinase-scaffold-phosphatase complex and uses it to bidirectionally regulate AMPA receptors and L-type channels.

    Evidence Live-cell FRET (~5 nm), electrophysiology, NFAT reporter and phosphorylation assays in HEK293 and hippocampal neurons (multiple studies)

    PMID:11943807 PMID:12114507 PMID:12354762 PMID:12507994

    Open questions at the time
    • Stoichiometry and oligomeric state of the complex not yet defined
    • Trafficking effects on CaV1.2 PKA-independent — mechanism unclear at this point
  6. 2007 High

    Connected the scaffold to excitation-transcription coupling, showing anchored calcineurin reads local L-type channel Ca2+ to activate NFAT.

    Evidence Co-IP, electrophysiology and NFAT reporter assays with dominant-negative AKAP in HEK293 and neurons

    PMID:17640527

    Open questions at the time
    • How NFAT itself is recruited to the complex not yet defined
  7. 2008 High

    Identified AKAP5 as the convergent platform for inflammatory TRPV1 sensitization, extending its role to nociception.

    Evidence Co-IP, TRPV1 C-terminus deletion mapping, electrophysiology and in vivo hyperalgesia assays

    PMID:18701070

    Open questions at the time
    • Relative contribution of each anchored enzyme to sensitization not dissected here
  8. 2010 High

    Broadened the scaffold's enzyme repertoire to adenylyl cyclases and extended its role to cardiac and GPCR signalosomes, establishing tissue-wide compartmentalized cAMP control.

    Evidence Co-IP, FRET, AC activity assays in AKAP150 KO brain, cardiac KO mice, and cAMP biosensors (multiple studies)

    PMID:20188672 PMID:20231277 PMID:20410303 PMID:20428246 PMID:20664520 PMID:20671242

    Open questions at the time
    • How AC isoform selectivity is achieved across tissues not fully mapped
    • D36 vs full-KO phenotype divergence mechanism partly unexplained
  9. 2011 High

    Defined the quaternary architecture and added PP1 regulation and palmitoylation-dependent raft targeting, explaining how the scaffold physically integrates multiple enzymes and is membrane-positioned.

    Evidence Native MS and cross-linking of reconstituted complex, SPR/phosphatase assays, palmitoylation mutagenesis with raft fractionation and AC8 assays (multiple studies)

    PMID:21273417 PMID:21464287 PMID:21561082 PMID:21562284 PMID:21771783

    Open questions at the time
    • In vivo relevance of PP1 inhibition not established
    • Which channel/receptor complexes depend on raft localization not fully cataloged
  10. 2012 High

    Revealed a paradoxical affinity-tuning principle: the calcineurin-anchoring motif competes with NFAT's docking peptide, so AKAP5 affinity sets NFAT output, and PKA feedback phosphorylates AC8 to shape cAMP dynamics.

    Evidence Structural binding analysis with mutagenesis, NFAT/calcineurin recruitment assays, AC8 S112A mutagenesis with FRET cAMP imaging (multiple studies)

    PMID:22343722 PMID:22677788 PMID:22693956 PMID:22976297 PMID:23259949

    Open questions at the time
    • Whether decoy-site tuning operates at endogenous expression levels unresolved
  11. 2013 High

    Established AC anchoring (not just PKA anchoring) as the critical node for β-adrenergic GluA1 phosphorylation and LTP, and validated the TRPV1-binding motif as an analgesic target in vivo.

    Evidence AKAP5 KO and D36 knock-in mice with LTP electrophysiology; TAT-peptide hyperalgesia assays (multiple studies)

    PMID:23649627 PMID:23699529 PMID:23889134

    Open questions at the time
    • Mechanism by which AC anchoring outweighs PKA anchoring not fully explained
  12. 2014 High

    Showed AKAP5 governs homeostatic synaptic scaling and cardiac CaN/CaMKII balance, broadening its plasticity and disease roles.

    Evidence AKAP5 RNAi and GluA1 S845 knockin, trafficking/electrophysiology; AKAP5 KO mice with echocardiography (multiple studies)

    PMID:25225170 PMID:25451194

    Open questions at the time
    • Causal chain from AKAP5 loss to cardiac dilatation only partly resolved
  13. 2015 High

    Identified DHHC2 as the enzyme controlling AKAP5 palmitoylation/endosomal targeting and showed scaffold coupling to STIM1/store-operated channels, linking lipid modification to plasticity and Ca2+ entry.

    Evidence DHHC2 RNAi with lipidated rescue mutant, spine imaging, electrophysiology; STIM1 T389 mutagenesis with ARC/CRAC recordings (multiple studies)

    PMID:25504574 PMID:25589740

    Open questions at the time
    • Regulation of DHHC2 activity itself unknown
    • How STIM1 phosphorylation discriminates ARC vs CRAC at structural level not defined
  14. 2017 High

    Defined the molecular switch for activity-dependent scaffold removal, showing CaMKII-driven depalmitoylation (not phosphorylation alone) drives synaptic removal during LTD, and that intrinsic disorder tunes anchored phosphatase drug sensitivity.

    Evidence CaMKII pharmacology and site mutagenesis with live spine imaging; negative-stain EM with live-cell sensors (multiple studies)

    PMID:28967377 PMID:29196604

    Open questions at the time
    • Identity of the depalmitoylating enzyme not established
    • How conformational ensembles map to specific functional states unresolved
  15. 2019 High

    Pinpointed the C-terminal leucine-zipper as the direct NFAT-recruitment determinant and assigned PKC-dependent GluA1 Ser831 phosphorylation to generation of Ca2+-permeable AMPARs.

    Evidence AKAP150 RNAi with LZ-mutant rescue, FRET/NFAT/Ca2+ assays; GluA1 phosphosite mutagenesis with I-V electrophysiology (multiple studies)

    PMID:30737285 PMID:31091162

    Open questions at the time
    • Structural basis of LZ-NFAT contact not solved
  16. 2021 High

    Quantified how scaffolding accelerates calcineurin-mediated suppression of PKA and dissected the Orai1-AKAP5-NFAT cytokine pathway, giving a kinetic and structural account of excitation-transcription coupling and PKA antagonism.

    Evidence In vitro reconstitution phosphatase assays with PKA reporters and LTD electrophysiology; NMR of the Orai1 N-terminus; cAMP nexus mapping; β-cell leptin FRET reporters (multiple studies)

    PMID:33082339 PMID:33617875 PMID:33941685 PMID:34458850 PMID:34612814

    Open questions at the time
    • Whether the ~10-fold calcineurin acceleration occurs at endogenous stoichiometry in vivo not confirmed
    • AC requirement for Orai1-linked cAMP appears cell-type-dependent
  17. 2022 Medium

    Established dynamic exchange kinetics of AKAP5 on Orai1, explaining how transient scaffold occupancy and NFAT recycling sustain transcription during continuous Ca2+ entry.

    Evidence FRAP, FCS, co-IP and NFAT1 translocation with mathematical kinetic modeling

    PMID:36317924

    Open questions at the time
    • Single-lab kinetic model awaits independent confirmation
    • Molecular driver of the rapid AKAP5 exchange not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how the many enzyme and channel modules are dynamically prioritized at a single AKAP5 scaffold within a cell, and which depalmitoylase and upstream signals control the activity-dependent assembly/disassembly cycle in vivo.
  • No full-length high-resolution structure of an assembled signalosome on a native channel
  • Depalmitoylating enzyme unidentified
  • Selectivity rules governing which partner complex forms in a given compartment are unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0060090 molecular adaptor activity 4 GO:0008092 cytoskeletal protein binding 2 GO:0008289 lipid binding 2
Localization
GO:0005886 plasma membrane 4 GO:0005856 cytoskeleton 3 GO:0005829 cytosol 2 GO:0005768 endosome 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-112316 Neuronal System 5 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-397014 Muscle contraction 3
Partners
ADCY8 (AC8)CACNA1C (CAV1.2)CALM1 (CALMODULIN)DLG1 (SAP97)ORAI1PPP3CA (CALCINEURIN A)PRKAR2 (PKA RII)PRKCB (PKC)
Complex memberships
AKAP79-PKA(RII)-calcineurin(PP2B)-CaM quaternary complexOrai1-AKAP79-calcineurin-NFAT1 complexRXFP1-AKAP79-AC2-β-arrestin2-PDE4D3 signalosomecaveolin-3/AC5-6/PKA/calcineurin/CaV1.2 cardiac T-tubule complex

Evidence

Reading pass · 54 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 AKAP79 functions as a scaffold protein that simultaneously binds three signaling enzymes—PKA, calcineurin (PP2B), and PKC—at distinct binding sites, coordinating their localization in mammalian neurons. Deletion analysis and binding studies (co-immunoprecipitation, subcellular co-distribution by immunofluorescence) Science High 8599116
1993 AKAP79 (AKAP75) contains two distinct non-contiguous N-terminal domains (residues 27–48 and 77–91) required for intracellular membrane/cytoskeletal targeting, and a C-terminal RII-binding (tethering) domain mapped to residues 392–413 where hydrophobic residues are essential for high-affinity PKA regulatory subunit binding. Deletion and scanning mutagenesis with subcellular fractionation and RII binding assays in HEK293 cells The Journal of biological chemistry High 8509414
1997 Ca²⁺/calmodulin binds AKAP79 with high affinity (KD ~28 nM) and competes with PKC for the same N-terminal region (residues 31–52), releasing inhibited PKC from the AKAP79 complex and increasing PKC activity at postsynaptic densities. Calmodulin binding assays, co-immunoprecipitation, PKC activity assays, immunofluorescence in hippocampal neurons The Journal of biological chemistry High 9202019
1998 AKAP79 membrane targeting is mediated by three basic/hydrophobic N-terminal regions (A: residues 31–52; B: 76–101; C: 116–145) that bind acidic phospholipids including PtdIns(4,5)P2; this binding is regulated by phosphorylation and Ca²⁺/calmodulin, and PKC or calmodulin activation releases AKAP79 from membrane fractions. GFP-based fluorescence imaging of deletion mutants, membrane vesicle lipid-binding assays, subcellular fractionation, phosphorylation assays in HEK293 cells and cortical neurons The EMBO journal High 9545238
1998 AKAP79 binds calcineurin A through residues 108–280 on AKAP79 and residues 30–98 and 311–336 on calcineurin A, independently of calcineurin B and at a site distinct from immunophilin-binding regions; overexpression of AKAP79 inhibits calcineurin-mediated NFAT dephosphorylation and activation in intact cells. Co-immunoprecipitation, truncation mapping, NFAT reporter assay in transfected cells The Journal of biological chemistry High 9765270
1999 AKAP79 binds and inhibits the conserved catalytic core of PKC (multiple conventional, novel, and atypical isoforms) through a mechanism involving the pseudosubstrate displacement by residues 31–52 (specifically Arg39 and Arg40); lipid activators or kinase activation are not required for the association. In vitro binding and kinase activity assays, endoproteinase proteolysis, mutagenesis of AKAP79 and PKCβII, co-immunoprecipitation and immunofluorescence in hippocampal neurons The Biochemical journal High 10510312
2001 AKAP79 regulates GRK2 membrane recruitment and β2AR phosphorylation by anchoring PKA, which directly phosphorylates GRK2 on Ser685, increasing Gβγ binding to GRK2 and enhancing GRK2 translocation to agonist-occupied receptor; S685A mutation or dominant-negative AKAP79 reduces GRK2-mediated receptor phosphorylation and internalization. Mutagenesis of GRK2 (S685A), dominant-negative AKAP79 expression, phosphorylation assays, receptor internalization assays in HEK293 cells The Journal of biological chemistry High 11278469
2001 AKAP79 directly associates with the inwardly rectifying potassium channel Kir2.1 via both N- and C-terminal intracellular domains of the channel, and this association enhances the channel's response to elevated intracellular cAMP. Co-immunoprecipitation from intact cells, GST pulldown with Kir2.1 intracellular domains, electrophysiology in transfected cells The Journal of biological chemistry Medium 11287423
2002 AKAP79 promotes basal PKA-mediated phosphorylation of GluR1 Ser845 and, through anchored PP2B and Ca²⁺ signaling, confers calcineurin-dependent downregulation of GluR1 receptor currents analogous to LTD; this requires PKA, Ser845, and PDZ-domain interaction between GluR1 and SAP97. Electrophysiology, co-immunoprecipitation, phosphorylation assays in HEK293 cells and hippocampal neurons The Journal of neuroscience High 11943807
2002 AKAP79 directly regulates cell-surface expression (trafficking) of L-type calcium channels (CaV1.2) via a polyproline sequence in the channel II–III cytoplasmic loop, independently of PKA activity. Extracellular epitope tagging of CaV1.2, immunoassays, whole-cell and single-channel electrophysiology in transfected cells The Journal of biological chemistry Medium 12114507
2002 The PP2B/calcineurin-binding site on AKAP79 is localized to residues 315–360; multiple determinants in this region bind directly to the calcineurin A subunit and inhibit phosphatase activity; peptides spanning residues 330–357 antagonize PP2B anchoring and attenuate PP2B-dependent downregulation of GluR1 currents. Cellular targeting assays with AKAP79 truncation/deletion mutants, in vitro binding and phosphatase activity assays, peptide antagonist electrophysiology in HEK293 cells The Journal of biological chemistry High 12354762
2002 FRET microscopy in living cells directly demonstrated that PKA-RII and calcineurin A subunits simultaneously bind AKAP79 at the plasma membrane cytoskeleton within ~5 nm of each other, forming a ternary kinase-scaffold-phosphatase complex; AKAP79 also regulates membrane localization of SAP97. FRET microscopy (immunofluorescence and live-cell FRET), subcellular localization in transfected cells The Journal of cell biology High 12507994
2003 AKAP79 directly interacts with the C-terminal domain of IQGAP1, forming an IQGAP1/AKAP79 complex that co-purifies with PKA in β-cells, potentially linking cAMP/PKA signaling with Ca²⁺/CaM and GTPase pathways. cAMP affinity chromatography, co-immunoprecipitation, direct binding assay with IQGAP1 C-terminal domain Journal of cellular biochemistry Medium 12938160
2005 AKAP79 is constitutively associated with the β2-adrenergic receptor and anchors PKA to mediate PKA-dependent phosphorylation of β2AR and switching of β2AR signaling to ERK activation via Gi; β-arrestin-recruited PDE4D5 desensitizes this AKAP79/PKA-mediated process. siRNA knockdown of specific PDE4 isoforms and AKAP79, co-immunoprecipitation, β2AR phosphorylation assays, ERK activation assays in HEK293B2 cells The Journal of biological chemistry High 16030021
2006 AKAP79-mediated targeting of PKA to the β1-adrenergic receptor promotes receptor recycling and functional resensitization; AKAP79, β1-AR, and PKA form a ternary complex at the β1-AR C-terminus; siRNA knockdown of AKAP79 prevents β1-AR recycling. siRNA knockdown, co-immunoprecipitation, FRET microscopy, PKA phosphorylation assays in HEK293 cells, SK-N-MC cells, and neonatal rat cortical neurons The Journal of biological chemistry High 16940053
2006 AKAP79 forms a complex with SAP97 at the PDZ-binding sequence (ESKV) at the β1-AR C-terminus, assembling a receptosome that targets PKA to β1-AR for Ser312 phosphorylation in the third intracellular loop, which is required for receptor recycling. Co-immunoprecipitation, domain deletion mutants, PKA phosphorylation assays, receptor trafficking assays in HEK293 cells The Journal of biological chemistry Medium 17170109
2007 AKAP79/150 directly interacts with CaV1.2 and co-targets PKA and calcineurin to L-type channels, conferring bidirectional regulation of L-type current; anchored calcineurin dominantly suppresses PKA enhancement of the channel; AKAP79/150-anchored calcineurin is required for NFATc4 activation by local Ca²⁺ influx through L-type channels. Co-immunoprecipitation, electrophysiology in HEK293 cells and hippocampal neurons, NFAT reporter assays, dominant-negative AKAP constructs Neuron High 17640527
2008 AKAP79/150 forms a complex with TRPV1, PKA, PKC, and calcineurin via a critical region in the TRPV1 C-terminus; disrupting this binding abrogates TRPV1 sensitization by bradykinin and PGE2, demonstrating that AKAP79/150 is a final common element for heat hyperalgesia. Co-immunoprecipitation, deletion mapping of TRPV1 C-terminus, TRPV1 electrophysiology in transfected cells and neurons, in vivo hyperalgesia assays Neuron High 18701070
2008 AKAP79 selectively enhances PKC-mediated phosphorylation of GluR1 Ser831 by localizing PKC near the receptor via SAP97, shifting the PKC dose-dependence ~20-fold so that low PKC concentrations are as effective as much higher CaMKII concentrations. Biochemical phosphorylation assays, electrophysiology of GluR1 currents in transfected cells with AKAP79 constructs The Journal of biological chemistry Medium 18305116
2010 AKAP79 associates with multiple adenylyl cyclase (AC) isoforms (AC5, AC6, AC9) via their N-terminal regions and residues 77–108 of AKAP79; this interaction places AC5/6 in proximity to synaptic AMPA receptors; loss of AKAP150 in mice decreases AMPA receptor-associated AC activity. Co-immunoprecipitation, FRET (intensity- and lifetime-based) in living cells, AC activity assays in brain extracts from AKAP150 KO mice, domain deletion mapping The Journal of biological chemistry High 20231277
2010 AKAP5 (AKAP79/150) organizes a caveolin-3-associated signaling complex in cardiac T-tubules comprising adenylyl cyclase 5/6, PKA, calcineurin, and a subpopulation of CaV1.2 channels; only this caveolin-3-associated CaV1.2 subpopulation is phosphorylated by PKA upon sympathetic stimulation; AKAP5 KO disrupts this complex, preventing normal calcium transients and PKA-dependent phosphorylation of ryanodine receptors and phospholamban. AKAP5 knockout mice, calcium imaging, electrophysiology, co-immunoprecipitation, PKA phosphorylation assays in cardiomyocytes Circulation research High 20671242
2010 AKAP79 alters the cellular pharmacology of anchored PKC, protecting it from certain ATP-competitive inhibitors; AKAP79-anchored PKC synchronizes muscarinic agonist-induced phosphorylation and KCNQ2 M-channel inhibition to optimize neuronal excitability. Dual fluorescent imaging/patch-clamp technique with CKAR kinase activity reporter, pharmacological profiling, electrophysiology in neurons Molecular cell High 20188672
2010 AKAP79/150 directly interacts with AC8, limiting AC8 sensitivity to intracellular Ca²⁺; this interaction was observed in HEK293 cells, pancreatic insulin-secreting cells, and hippocampal neurons. Co-immunoprecipitation, high-resolution live-cell imaging in multiple cell types endogenously expressing both proteins The Journal of biological chemistry Medium 20410303
2010 AKAP5 knockout in mice delocalizes PKA from hippocampus and striatum (redistributing it to dendritic shafts via MAP2 binding); the D36 mutant lacking only the PKA binding domain produces more severe electrophysiological and behavioral deficits than complete KO, indicating that targeting calcineurin or other binding partners without the balancing PKA disrupts synaptic plasticity. Genetic KO and knockin (D36) mouse lines, immunofluorescence, co-immunoprecipitation, electrophysiology, behavioral tests PloS one High 20428246
2010 Ca²⁺/calmodulin disrupts AKAP79/150 interaction with KCNQ2–5 (but not KCNQ1) channels as shown by TIRF/FRET; this disruption prevents AKAP79-mediated sensitization of KCNQ2/3 channels to muscarinic inhibition, while PIP2 depletion does not affect AKAP79 membrane localization. TIRF/FRET microscopy, perforated patch-clamp electrophysiology, dominant-negative calmodulin, cotransfection in CHO cells The Journal of neuroscience High 20147557
2011 AKAP79 dimerizes through K328-K328 and K333-K333 cross-links; the reconstituted AKAP79-PP2B-RII-CaM complex has a molecular mass of ~466 kDa consisting of dimeric AKAP79 coordinating two RII homodimers, four PP2B heterodimers, and two calmodulin molecules; Ca²⁺/CaM binding activates anchored phosphatases by generating a second interface. Native mass spectrometry, chemical cross-linking, in vitro reconstitution of quaternary complex, quantitative biochemical analysis Proceedings of the National Academy of Sciences High 21464287
2011 AKAP79/150-anchored PKA controls Kv4.2 surface expression; the C-terminal domain of Kv4.2 interacts with an internal region of AKAP79/150 overlapping its MAGUK-binding domain; disrupting PKA anchoring decreases neuronal excitability while preventing calcineurin-mediated dephosphorylation increases excitability. Co-immunoprecipitation, pulldown, AKAP79/150 KO neurons, PKA anchoring disruption (Ht31 peptide), electrophysiology in hippocampal neurons The Journal of neuroscience Medium 21273417
2011 AKAP79 is identified as a novel PP1 regulatory subunit; it directly binds PP1 catalytic subunit through a consensus FxxR/KxR/K motif in residues 1–44 and a second domain in residues 150–250; AKAP79 inhibits PP1 activity (IC50 ~811 nM) in a substrate-dependent manner but does not inhibit PP1 dephosphorylation of phospho-PSD-95. Co-immunoprecipitation from rat brain, pulldown with purified proteins, phosphatase activity assays, surface plasmon resonance, peptide mapping Biochemistry Medium 21561082
2011 Palmitoylation of AKAP79 at two N-terminal cysteines targets it to lipid rafts; mutation of these cysteines excludes AKAP79 from rafts, alters membrane diffusion behavior, and abolishes AKAP79-dependent regulation of SOCE-stimulated AC8 activity and PKA-dependent phosphorylation of raft proteins. Pharmacological palmitoylation inhibition, site-directed mutagenesis of Cys residues, lipid raft fractionation, FRAP analysis, AC8 activity assays in HEK293 cells The Journal of biological chemistry High 21771783
2011 AKAP79/150-mediated PKC anchoring is specifically required for muscarinic M1 (and angiotensin II) receptor suppression of M-type (KCNQ) K⁺ currents in SCG neurons, but not for bradykinin or purinergic suppression; FRET showed strong AKAP79 association with M1 and AT1 receptors and KCNQ2/3, but weak association with P2Y6 or B2 receptors. AKAP150 KO mice, transfection of ΔA-AKAP79 (no PKC binding), FRET under TIRF microscopy, perforated patch-clamp in SCG neurons The Journal of neuroscience High 21562284
2012 The IAIIIT anchoring motif in AKAP79 (residues forming a short linear motif) binds the same surface of calcineurin as the PxIxIT recognition peptide of NFAT but with higher affinity; increasing calcineurin-AKAP affinity paradoxically impairs NFAT activation by slowing calcineurin release and sequestering it as 'decoy' sites. Structural binding analysis, mutagenesis of AKAP79 anchoring sequence, NFAT activation assays, calcineurin recruitment measurements Nature structural & molecular biology High 22343722
2012 AKAP79/150-anchored calcineurin and L-type Ca²⁺ channel activation drive KCNQ2/3 transcriptional upregulation via NFAT in hippocampal neurons; AKAP150 KO mice fail to upregulate KCNQ2/3 transcription after drug-induced seizures, indicating a negative feedback mechanism on neuronal excitability. Neuronal activity manipulation, NFAT reporter assays, AKAP150 KO mice, qRT-PCR of KCNQ2/3 mRNA in seizure model Neuron High 23259949
2012 AKAP79 interacts with caldendrin (a neuronal Ca²⁺-binding protein) at a site overlapping the calmodulin-binding region; caldendrin competes with calmodulin for binding to AKAP79 with similar affinity (KD ~20 nM vs ~30 nM for CaM), but through an induced-fit mechanism with a slow rearrangement step and Ca²⁺-independent binding component. Pulldown experiments, surface plasmon resonance biosensor kinetic analysis Journal of neurochemistry Medium 22693956
2012 AKAP79 modulation of CaV1.2 membrane expression occurs through disruption of an autoinhibitory intramolecular interaction between the channel II–III linker and distal C-terminus; AKAP79 directly interacts with the distal CaV1.2 C-terminus, competing with its association to the II–III linker. Mutagenesis of polyproline domains, co-immunoprecipitation, channel trafficking assays in transfected cells Channels Medium 22677788
2012 PKA recruited to AC8 via AKAP79 phosphorylates AC8 at Ser112, providing a negative feedback mechanism that reduces the on-rate of cAMP production during Ca²⁺ oscillations. Site-directed mutagenesis of AC8 (S112A), FRET-based cAMP measurements during Ca²⁺ oscillations, co-immunoprecipitation Journal of cell science High 22976297
2013 The AKAP79 region between amino acids 326–336 mediates binding to TRPV1; a TAT-conjugated peptide mimicking this domain inhibits TRPV1 sensitization in vitro and inflammatory hyperalgesia in vivo without affecting basal pain thresholds. FRET, co-immunoprecipitation, TRPV1 membrane trafficking assays, in vivo hyperalgesia assay with TAT-peptide The Journal of neuroscience High 23699529
2013 AKAP5 (AKAP79/150) anchors adenylyl cyclase (AC) to postsynaptic sites and this AC anchoring is required for β-adrenergic stimulation-induced phosphorylation of GluA1 Ser845 and for theta-frequency-induced LTP; AC anchoring (disrupted in AKAP5 KO) is more critical than PKA anchoring alone (disrupted in D36 mice) for this process. AKAP5 KO and D36 (PKA-binding-deleted) knock-in mice, phosphorylation assays, LTP electrophysiology in acute forebrain slices The Journal of biological chemistry High 23649627
2013 AKAP79 recruits PKC to activate AC2 and generates localized cAMP upon Gq-coupled muscarinic receptor stimulation; PKA anchored to AKAP79 activates PDE4 to degrade this cAMP; calcineurin anchored to AKAP79 is not involved in this pathway. Live-cell cAMP imaging, siRNA knockdown of AKAP79 components, pharmacological dissection in HEK293 cells The Biochemical journal Medium 23889134
2014 AKAP5 scaffold is required for PKA-GluA1 coupling during homeostatic plasticity; knockdown of AKAP5 blocks synaptic scaling up, which requires PKA-mediated phosphorylation of GluA1 S845; scaling down involves loss of PKA from synapses, and scaling up involves enhanced synaptic PKA activity regulated by AKAP5. AKAP5 RNAi knockdown, GluA1 S845 knockin mutant, phosphorylation assays, electrophysiology, surface AMPAR trafficking assays in neurons Neuron High 25451194
2014 AKAP5 controls calcineurin (CaN) and CaMKII activity in cardiac myocytes; loss of AKAP5 enhances CaN and CaMKII activities, interferes with β1-AR recycling through CaN binding to AKAP5, and leads to cardiac dilatation and dysfunction. AKAP5 KO mice, NFAT-luciferase reporter, echocardiography, biochemical assays, pharmacological rescue with carvedilol Cardiovascular research Medium 25225170
2015 DHHC2 palmitoyl acyltransferase, resident in recycling endosomes, directly palmitoylates AKAP79/150 to regulate its targeting to recycling endosomes; DHHC2 knockdown disrupts recycling endosome exocytosis, dendritic spine enlargement, AKAP recruitment to spines, and LTP-stimulated AMPAR delivery; a palmitoylation-independent lipidated AKAP mutant rescues these deficits. RNAi knockdown of DHHC2, palmitoylation-independent AKAP rescue mutant, live imaging of spine exocytosis, electrophysiology in hippocampal neurons The Journal of neuroscience High 25589740
2015 AKAP79 constitutively associates with plasma membrane STIM1 and mediates PKA phosphorylation of STIM1 Thr389, which is necessary for activation of store-independent ARC channels but actually inhibits STIM1's ability to activate store-operated CRAC channels. AKAP79 knockdown, STIM1 T389 mutagenesis, ARC and CRAC channel electrophysiology, PKA activity assays The Journal of physiology High 25504574
2017 CaMKII mediates LTD-induced synaptic removal of AKAP79/150 by phosphorylating its N-terminal polybasic targeting domain (inhibiting F-actin association) and by promoting depalmitoylation at two N-terminal Cys residues; depalmitoylation (not phosphorylation per se) is required for AKAP79/150 spine removal and LTD-induced spine shrinkage; autonomous CaMKII activity preferentially phosphorylates AKAP79/150 compared with Ca²⁺/CaM-stimulated CaMKII. CaMKII inhibitors and constitutively active CaMKII, mutagenesis of palmitoylation sites and phosphorylation sites, live imaging of spine morphology, AKAP trafficking in hippocampal neurons during LTD The Journal of biological chemistry High 29196604
2017 Intrinsic disorder in AKAP79 allows conformational flexibility in PP2B engagement; the sole PP2B-anchoring determinant is a short linear motif (residues 337–343); Ca²⁺/calmodulin activation condenses diverse conformational variants into a uniform 178 Å population and engages a Leu-Lys-Ile-Pro sequence (residues 125–128) that occupies a PP2B binding pocket shared with cyclosporin, fine-tuning anchored phosphatase drug sensitivity. Negative-stain electron microscopy structural analysis, live-cell fluorescent activity sensor imaging, mutagenesis eLife High 28967377
2019 AKAP79 directly interacts with NFAT via its C-terminal leucine-zipper (LZ) domain; disrupting this LZ interaction abolishes depolarization-stimulated NFAT signaling in hippocampal neurons while preserving the AKAP-LTCC interaction and LTCC function; AKAP79 thus recruits NFAT to the LTCC signaling complex to promote its activation by anchored calcineurin. RNAi knockdown of AKAP150 with human AKAP79 LZ-mutant replacement, FRET, Ca²⁺ imaging, electrophysiology, NFAT reporter, FRAP and FCS in hippocampal neurons Molecular biology of the cell High 31091162
2019 AKAP79-anchored PKC (not other AKAP79-signaling components) drives the appearance of Ca²⁺-permeable (GluA2-lacking) AMPARs primarily through GluA1 Ser831 phosphorylation; this generates CP-AMPARs under conditions where CI-AMPARs normally predominate. Electrophysiology (current-voltage relationships), GluA1 phosphosite mutagenesis, AKAP79 domain mutants in transfected cells The Journal of biological chemistry Medium 30737285
2020 AKAP5 organizes a nanocomplex of P2Y11/P2Y11-like receptors, AC5, PKA, and CaV1.2 at the plasma membrane of arterial myocytes; disruption of AKAP5 function blocks glucose- and P2Y11 agonist-induced cAMP synthesis, CaV1.2 potentiation, vasoconstriction, and decreased blood flow. AKAP5 null mice and arterial myocytes, proximity ligation assay for nanocomplexes, cAMP assays, electrophysiology, vasoconstriction assays Nature communications High 33082339
2020 STIM2 recruits Orai1/STIM1 to ER-PM junctions in response to ER-Ca²⁺ depletion, promoting assembly with AKAP79 to couple Orai1 channel function to NFAT1 activation; STIM2 knockdown attenuates NFAT1 activation and Orai1-AKAP79 assembly without substantially reducing Orai1/STIM1 clustering or global Ca²⁺ increases. STIM2 knockdown, STIM1ΔK mutant, co-immunoprecipitation, Ca²⁺ imaging, NFAT1 nuclear translocation assays Proceedings of the National Academy of Sciences High 32601188
2021 AKAP79 enables calcineurin to dephosphorylate PKA type II regulatory subunits at a rate ~10-fold higher than without scaffolding; this allows calcineurin to suppress PKA activity by increasing catalytic subunit capture rate without altering cAMP levels, and this mechanism contributes to hippocampal LTD. In vitro reconstitution phosphatase assays, fluorescent PKA activity reporter (AKAR), kinetic modeling, hippocampal neuron LTD electrophysiology eLife High 34612814
2021 The N-terminus of Orai1 (but not Orai2, Orai3, or a shorter Orai1 isoform) directly interacts with AKAP79; NMR structural analysis reveals the AKAP-binding domain has a compact shape with proline-driven turns; this interaction is essential for NFAT1 activation by local Ca²⁺ entry and cytokine production. NMR structural analysis of AKAP79-binding domain, co-immunoprecipitation, domain deletion/truncation of Orai isoforms, NFAT1 reporter assays, cytokine production assays Proceedings of the National Academy of Sciences High 33941685
2021 AKAP79 coordinates PKA and PDE4 in a cAMP signaling nexus adjacent to Orai1; both PKA and PDE4 associate with AKAP79 and relocalize close to Orai1 after stimulation; in HEK293 cells, which lack functional Ca²⁺-activated adenylyl cyclases including AC8, Ca²⁺ entry through Orai1 does not increase cAMP levels despite AKAP79-Orai1 association. FRET-based cAMP sensors (AKAP79-CUTie), mass spectrometry, PCR, bulk cAMP and PKA activity measurements in HEK293 cells Function Medium 34458850
2021 AKAP79/150 coordinates leptin-induced PKA signaling at the cell membrane in pancreatic β-cells; leptin increases PKA activity at the membrane via NMDAR-CaMKKβ-AMPK signaling in an AKAP79/150-dependent manner; disrupting PP2B anchoring to AKAP79/150 elevates basal PKA signaling and increases surface KATP channels even without leptin. FRET-based PKA activity reporters, AKAP79/150 genetic knockdown and rescue, dominant-negative PP2B anchoring disruption, KATP channel trafficking assays in MIN6 β-cells The Journal of biological chemistry Medium 33617875
2010 A pre-assembled RXFP1-AKAP79-AC2-β-arrestin 2-PDE4D3 signalosome mediates sub-picomolar relaxin signaling; AC2 is functionally coupled to RXFP1 through AKAP79 binding to helix 8 of the receptor; PKA-activated PDE4D3 scaffolded via β-arrestin 2 tonically opposes AC2 activity. cAMP biosensors in single cells, co-immunoprecipitation, domain mapping (helix 8 of RXFP1) The EMBO journal Medium 20664520
2022 The AKAP79-Orai1 interaction is considerably more transient than STIM1-Orai1; free AKAP79 (with calcineurin and NFAT1) can rapidly replace AKAP79 devoid of NFAT1 on Orai1 during continuous Ca²⁺ entry; Ca²⁺ nanodomains near Orai1 activate nearly the entire cytosolic NFAT1 pool, and recycling of inactive NFAT1 from cytoplasm to AKAP79 sustains excitation-transcription coupling. FRAP, FCS, co-immunoprecipitation, NFAT1 translocation assays, mathematical kinetic modeling Molecular and cellular biology Medium 36317924

Source papers

Stage 0 corpus · 91 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Coordination of three signaling enzymes by AKAP79, a mammalian scaffold protein. Science (New York, N.Y.) 479 8599116
2007 AKAP79/150 anchoring of calcineurin controls neuronal L-type Ca2+ channel activity and nuclear signaling. Neuron 285 17640527
2008 Proinflammatory mediators modulate the heat-activated ion channel TRPV1 via the scaffolding protein AKAP79/150. Neuron 218 18701070
1998 Membrane-targeting sequences on AKAP79 bind phosphatidylinositol-4, 5-bisphosphate. The EMBO journal 204 9545238
2002 Regulation of GluR1 by the A-kinase anchoring protein 79 (AKAP79) signaling complex shares properties with long-term depression. The Journal of neuroscience : the official journal of the Society for Neuroscience 183 11943807
2005 RNA silencing identifies PDE4D5 as the functionally relevant cAMP phosphodiesterase interacting with beta arrestin to control the protein kinase A/AKAP79-mediated switching of the beta2-adrenergic receptor to activation of ERK in HEK293B2 cells. The Journal of biological chemistry 170 16030021
2010 Sympathetic stimulation of adult cardiomyocytes requires association of AKAP5 with a subpopulation of L-type calcium channels. Circulation research 141 20671242
2001 Regulation of membrane targeting of the G protein-coupled receptor kinase 2 by protein kinase A and its anchoring protein AKAP79. The Journal of biological chemistry 135 11278469
2014 PKA-GluA1 coupling via AKAP5 controls AMPA receptor phosphorylation and cell-surface targeting during bidirectional homeostatic plasticity. Neuron 132 25451194
2012 Balanced interactions of calcineurin with AKAP79 regulate Ca2+-calcineurin-NFAT signaling. Nature structural & molecular biology 130 22343722
2002 Mapping the protein phosphatase-2B anchoring site on AKAP79. Binding and inhibition of phosphatase activity are mediated by residues 315-360. The Journal of biological chemistry 124 12354762
2002 Trafficking of L-type calcium channels mediated by the postsynaptic scaffolding protein AKAP79. The Journal of biological chemistry 112 12114507
2000 AKAP79 and the evolution of the AKAP model. FEBS letters 112 10878251
2002 Imaging kinase--AKAP79--phosphatase scaffold complexes at the plasma membrane in living cells using FRET microscopy. The Journal of cell biology 109 12507994
1997 Regulation of the AKAP79-protein kinase C interaction by Ca2+/Calmodulin. The Journal of biological chemistry 99 9202019
2010 Interaction with AKAP79 modifies the cellular pharmacology of PKC. Molecular cell 96 20188672
2010 AKAP79 interacts with multiple adenylyl cyclase (AC) isoforms and scaffolds AC5 and -6 to alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptors. The Journal of biological chemistry 95 20231277
1993 Characterization of distinct tethering and intracellular targeting domains in AKAP75, a protein that links cAMP-dependent protein kinase II beta to the cytoskeleton. The Journal of biological chemistry 79 8509414
2011 Architecture and dynamics of an A-kinase anchoring protein 79 (AKAP79) signaling complex. Proceedings of the National Academy of Sciences of the United States of America 78 21464287
1999 Mechanism of A-kinase-anchoring protein 79 (AKAP79) and protein kinase C interaction. The Biochemical journal 75 10510312
2011 Palmitoylation targets AKAP79 protein to lipid rafts and promotes its regulation of calcium-sensitive adenylyl cyclase type 8. The Journal of biological chemistry 74 21771783
2010 Mutations in AKAP5 disrupt dendritic signaling complexes and lead to electrophysiological and behavioral phenotypes in mice. PloS one 73 20428246
2012 Activity-dependent transcriptional regulation of M-Type (Kv7) K(+) channels by AKAP79/150-mediated NFAT actions. Neuron 72 23259949
1998 AKAP79 inhibits calcineurin through a site distinct from the immunophilin-binding region. The Journal of biological chemistry 72 9765270
2006 AKAP79-mediated targeting of the cyclic AMP-dependent protein kinase to the beta1-adrenergic receptor promotes recycling and functional resensitization of the receptor. The Journal of biological chemistry 71 16940053
2010 Sub-picomolar relaxin signalling by a pre-assembled RXFP1, AKAP79, AC2, beta-arrestin 2, PDE4D3 complex. The EMBO journal 67 20664520
2010 AKAP79/150 interacts with AC8 and regulates Ca2+-dependent cAMP synthesis in pancreatic and neuronal systems. The Journal of biological chemistry 66 20410303
2006 Assembly of an SAP97-AKAP79-cAMP-dependent protein kinase scaffold at the type 1 PSD-95/DLG/ZO1 motif of the human beta(1)-adrenergic receptor generates a receptosome involved in receptor recycling and networking. The Journal of biological chemistry 65 17170109
2015 The palmitoyl acyltransferase DHHC2 regulates recycling endosome exocytosis and synaptic potentiation through palmitoylation of AKAP79/150. The Journal of neuroscience : the official journal of the Society for Neuroscience 61 25589740
2013 Adenylyl cyclase anchoring by a kinase anchor protein AKAP5 (AKAP79/150) is important for postsynaptic β-adrenergic signaling. The Journal of biological chemistry 58 23649627
2001 Targeting of an A kinase-anchoring protein, AKAP79, to an inwardly rectifying potassium channel, Kir2.1. The Journal of biological chemistry 56 11287423
2014 G protein-coupled receptor 30 (GPR30) forms a plasma membrane complex with membrane-associated guanylate kinases (MAGUKs) and protein kinase A-anchoring protein 5 (AKAP5) that constitutively inhibits cAMP production. The Journal of biological chemistry 54 24962572
2010 Ca2+/calmodulin disrupts AKAP79/150 interactions with KCNQ (M-Type) K+ channels. The Journal of neuroscience : the official journal of the Society for Neuroscience 53 20147557
2011 AKAP79/150 signal complexes in G-protein modulation of neuronal ion channels. The Journal of neuroscience : the official journal of the Society for Neuroscience 50 21562284
2021 The N terminus of Orai1 couples to the AKAP79 signaling complex to drive NFAT1 activation by local Ca2+ entry. Proceedings of the National Academy of Sciences of the United States of America 49 33941685
2017 CaMKII regulates the depalmitoylation and synaptic removal of the scaffold protein AKAP79/150 to mediate structural long-term depression. The Journal of biological chemistry 46 29196604
2011 AKAP79/150 impacts intrinsic excitability of hippocampal neurons through phospho-regulation of A-type K+ channel trafficking. The Journal of neuroscience : the official journal of the Society for Neuroscience 46 21273417
2008 AKAP79 selectively enhances protein kinase C regulation of GluR1 at a Ca2+-calmodulin-dependent protein kinase II/protein kinase C site. The Journal of biological chemistry 46 18305116
2008 Stable membrane expression of postsynaptic CaV1.2 calcium channel clusters is independent of interactions with AKAP79/150 and PDZ proteins. The Journal of neuroscience : the official journal of the Society for Neuroscience 46 19091974
2004 Modulation of dopamine mediated phosphorylation of AMPA receptors by PSD-95 and AKAP79/150. Neuropharmacology 46 15458848
2009 Ca2+/calmodulin-dependent protein kinase II binds to and phosphorylates a specific SAP97 splice variant to disrupt association with AKAP79/150 and modulate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor (AMPAR) activity. The Journal of biological chemistry 45 19858198
2013 Role of AKAP79/150 protein in β1-adrenergic receptor trafficking and signaling in mammalian cells. The Journal of biological chemistry 44 24121510
2013 Mapping the binding site of TRPV1 on AKAP79: implications for inflammatory hyperalgesia. The Journal of neuroscience : the official journal of the Society for Neuroscience 40 23699529
2020 STIM2 targets Orai1/STIM1 to the AKAP79 signaling complex and confers coupling of Ca2+ entry with NFAT1 activation. Proceedings of the National Academy of Sciences of the United States of America 38 32601188
2020 AKAP5 complex facilitates purinergic modulation of vascular L-type Ca2+ channel CaV1.2. Nature communications 38 33082339
2006 G-Protein-coupled receptor-associated A-kinase anchoring proteins: AKAP79 and AKAP250 (gravin). European journal of cell biology 37 16442664
2005 Beta-arrestin-recruited phosphodiesterase-4 desensitizes the AKAP79/PKA-mediated switching of beta2-adrenoceptor signalling to activation of ERK. Biochemical Society transactions 35 16246112
2008 G-protein-coupled receptor-associated A-kinase anchoring proteins AKAP5 and AKAP12: differential signaling to MAPK and GPCR recycling. Journal of molecular signaling 33 19055733
2019 AKAP79/150 recruits the transcription factor NFAT to regulate signaling to the nucleus by neuronal L-type Ca2+ channels. Molecular biology of the cell 32 31091162
2003 Identification of an IQGAP1/AKAP79 complex in beta-cells. Journal of cellular biochemistry 32 12938160
2000 Localization of the A kinase anchoring protein AKAP79 in the human hippocampus. The European journal of neuroscience 31 10762347
2014 Carvedilol reverses cardiac insufficiency in AKAP5 knockout mice by normalizing the activities of calcineurin and CaMKII. Cardiovascular research 30 25225170
2012 A key phosphorylation site in AC8 mediates regulation of Ca(2+)-dependent cAMP dynamics by an AC8-AKAP79-PKA signalling complex. Journal of cell science 30 22976297
2013 AKAP79, PKC, PKA and PDE4 participate in a Gq-linked muscarinic receptor and adenylate cyclase 2 cAMP signalling complex. The Biochemical journal 27 23889134
2017 Intrinsic disorder within AKAP79 fine-tunes anchored phosphatase activity toward substrates and drug sensitivity. eLife 24 28967377
2015 Anchoring protein AKAP79-mediated PKA phosphorylation of STIM1 determines selective activation of the ARC channel, a store-independent Orai channel. The Journal of physiology 24 25504574
2010 Ca2+/calmodulin-dependent protein kinase II inhibitors disrupt AKAP79-dependent PKC signaling to GluA1 AMPA receptors. The Journal of biological chemistry 24 21156788
2011 A Potential Role for a Genetic Variation of AKAP5 in Human Aggression and Anger Control. Frontiers in human neuroscience 23 22232585
2008 G-protein-coupled receptor-associated A-kinase anchoring proteins AKAP5 and AKAP12: differential trafficking and distribution. Cellular signalling 19 18950703
2011 Identification of AKAP79 as a protein phosphatase 1 catalytic binding protein. Biochemistry 18 21561082
2005 Differential expression of protein kinase A, AKAP79, and PP2B in pregnant human myometrial membranes prior to and during labor. Journal of the Society for Gynecologic Investigation 18 15914039
2021 AKAP79 enables calcineurin to directly suppress protein kinase A activity. eLife 17 34612814
2021 AKAP79 Orchestrates a Cyclic AMP Signalosome Adjacent to Orai1 Ca2+ Channels. Function (Oxford, England) 15 34458850
2015 Curcumin Protects Neurons from Glutamate-Induced Excitotoxicity by Membrane Anchored AKAP79-PKA Interaction Network. Evidence-based complementary and alternative medicine : eCAM 15 26170881
2021 AKAP79/150 coordinates leptin-induced PKA signaling to regulate KATP channel trafficking in pancreatic β-cells. The Journal of biological chemistry 14 33617875
2019 Preferential generation of Ca2+-permeable AMPA receptors by AKAP79-anchored protein kinase C proceeds via GluA1 subunit phosphorylation at Ser-831. The Journal of biological chemistry 14 30737285
2012 AKAP79 modulation of L-type channels involves disruption of intramolecular interactions in the CaV1.2 subunit. Channels (Austin, Tex.) 14 22677788
2012 AKAP79/150 interacts with the neuronal calcium-binding protein caldendrin. Journal of neurochemistry 14 22693956
2011 AKAP12 and AKAP5 form higher-order hetero-oligomers. Journal of molecular signaling 14 21831305
2015 Mechanisms and dynamics of AKAP79/150-orchestrated multi-protein signalling complexes in brain and peripheral nerve. The Journal of physiology 13 25653013
2018 Targeting FRET-Based Reporters for cAMP and PKA Activity Using AKAP79. Sensors (Basel, Switzerland) 12 29976855
2011 AKAP5 and AKAP12 Form Homo-oligomers. Journal of molecular signaling 12 21554706
2013 Increased density of AKAP5-expressing neurons in the anterior cingulate cortex of subjects with bipolar disorder. Journal of psychiatric research 11 23462372
2022 Nuanced Interactions between AKAP79 and STIM1 with Orai1 Ca2+ Channels at Endoplasmic Reticulum-Plasma Membrane Junctions Sustain NFAT Activation. Molecular and cellular biology 9 36317924
2010 The contribution of AKAP5 in amylase secretion from mouse parotid acini. American journal of physiology. Cell physiology 9 20164376
2012 Kinetic and mechanistic differences in the interactions between caldendrin and calmodulin with AKAP79 suggest different roles in synaptic function. Journal of molecular recognition : JMR 8 22996592
2003 Expression and intracellular localization of protein phosphatases 2A and 2B, protein kinase a, A-Kinase anchoring protein (AKAP79), and binding of the regulatory (RII) subunit of protein kinase a to AKAP79 in human myometrium. Journal of the Society for Gynecologic Investigation 7 14519485
2015 Modified sympathetic nerve regulation in AKAP5-null mice. Biochemical and biophysical research communications 6 26713362
2014 AKAP5 keeps L-type channels and NFAT on their toes. Cell reports 5 24926793
2001 Development-related expression of AKAP79 in the striatal compartments of the human brain. Cells, tissues, organs 5 11275698
2015 AKAP5 signaling complexes: focal points and functional properties. Neuro endocrinology letters 4 25789584
2012 "Shaping" of cell signaling via AKAP-tethered PDE4D: Probing with AKAR2-AKAP5 biosensor. Journal of molecular signaling 4 22583680
2006 Contextual utilization of enzymes in discrete AKAP79/150 signalling complexes. European journal of cell biology 4 16460836
2024 Akap5 links synaptic dysfunction to neuroinflammatory signaling in a mouse model of infantile neuronal ceroid lipofuscinosis. Frontiers in synaptic neuroscience 3 38798824
2020 AKAP5 anchors PKA to enhance regulation of the HERG channel. The international journal of biochemistry & cell biology 3 32173522
2019 Maturation of thalamocortical synapses in the somatosensory cortex depends on neocortical AKAP5 expression. Neuroscience letters 3 31310785
2004 AKAP79 increases the functional expression of skeletal muscle Ca2+ channels in Xenopus oocytes. Biochemical and biophysical research communications 3 15003529
2022 Metoprolol Mitigates Ischemic Heart Remodeling and Fibrosis by Increasing the Expression of AKAP5 in Ischemic Heart. Oxidative medicine and cellular longevity 2 36238650
2025 Unveiling the significance of AKAP79/150 in the nervous system disorders: An emerging opportunity for future therapies? Neurobiology of disease 1 39864527
2026 Maternal exercise improves vascular function in hypertensive offspring via A-kinase anchoring protein 150 gene (Akap5) epigenetic modifications. British journal of pharmacology 0 41640285
2023 Retracted: Metoprolol Mitigates Ischemic Heart Remodeling and Fibrosis by Increasing the Expression of AKAP5 in Ischemic Heart. Oxidative medicine and cellular longevity 0 37810553

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