Affinage

AKAP13

A-kinase anchor protein 13 · UniProt Q12802

Length
2813 aa
Mass
307.6 kDa
Annotated
2026-06-09
52 papers in source corpus 31 papers cited in narrative 31 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

AKAP13 (AKAP-Lbc) is a dual-function scaffold that simultaneously anchors protein kinase A (PKA) and acts as a Gα12-activated, RhoA-selective guanine nucleotide exchange factor (GEF), thereby coupling GPCR signaling to actin cytoskeleton remodeling and transcriptional reprogramming (PMID:11546812, PMID:11696353). Its DH-PH catalytic module engages RhoA-GDP through an N-terminal 'GEF switch' that undergoes a conformational change upon binding, with the PH domain dispensable for nucleotide exchange (PMID:25186459), and a distinct C-terminal region confers selective coupling to Gα12 over Gα13 (PMID:31051012). The GEF activity is held in check by an integrated network of negative regulators: anchored-PKA phosphorylation of Ser1565 recruits 14-3-3 (PMID:15229649), C-terminal leucine-zipper homo-oligomerization is required for that inhibition (PMID:15691829), and LC3 binding to the N-terminal regulatory region suppresses RhoA engagement (PMID:19696020). Beyond its GEF role, AKAP13 nucleates multikinase complexes—coordinating PKCη-dependent PKD activation (PMID:15383279), assembling a PKNα/MLTK/MKK3/p38α module downstream of α1-adrenergic receptors (PMID:21224381), and scaffolding the KSR-1/RAF/MEK/ERK cassette via PKA phosphorylation of KSR-1 (PMID:21102438). Through these outputs it drives pathological cardiac hypertrophy via PKD-dependent HDAC5 nuclear export and MEF2 transcription (PMID:18951085, PMID:20139090, PMID:24161911), and is essential for embryonic cardiac development (PMID:20139090). AKAP13 also positions PKA toward diverse effectors to control transcription and cell fate, including ERα Ser305 phosphorylation and tamoxifen resistance (PMID:26272591), CREB1 activation (PMID:36401072), and PKA-mediated phosphorylation of Raptor (Ser791) to inhibit mTORC1 (PMID:34673774). It additionally contributes to cell migration through polarized leading-edge PKA gradients and integrin/LPA-driven RhoA signaling (PMID:19106088, PMID:22049212). The AKAP13/Lbc locus also encodes the HA-3 minor histocompatibility antigen (PMID:12663445).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2001 High

    Established AKAP13 as a bifunctional protein that both anchors PKA and acts as a Rho-selective GEF activated by Gα12, defining its core molecular identity.

    Evidence Co-immunoprecipitation, fibroblast overexpression, stress fiber assays, and selective Gα12 expression; endogenous Ht31 co-IP of RhoA from primary renal cells

    PMID:11546812 PMID:11696353

    Open questions at the time
    • Did not resolve how PKA anchoring and GEF activity are coupled
    • No structural basis for RhoA selectivity
  2. 2003 High

    Defined the AKAP13/Lbc locus as the source of the HA-3 minor histocompatibility antigen, explaining differential immunogenicity through allele-specific proteasomal processing.

    Evidence Mass spectrometry peptide identification, HLA binding, TAP transport, and proteasome digestion assays

    PMID:12663445

    Open questions at the time
    • Unrelated to the scaffold/GEF mechanism
    • Does not address physiological role of the full-length protein
  3. 2004 High

    Revealed that anchored-PKA phosphorylation of Ser1565 recruits 14-3-3 to inhibit GEF activity, establishing PKA as a built-in negative regulator of AKAP13's own Rho output.

    Evidence Co-IP, mutagenesis, cAMP elevation, and Rho-GEF activity assays

    PMID:15229649

    Open questions at the time
    • Did not address oligomerization requirement
    • Structural mechanism of inhibition unresolved
  4. 2004 High

    Showed AKAP13 assembles a PKD activation scaffold coordinating PKCη and PKA, demonstrating its capacity to integrate two kinases to activate a third.

    Evidence Co-IP, kinase assays, immunofluorescence

    PMID:15383279

    Open questions at the time
    • Downstream PKD transcriptional targets not yet defined
    • Cardiac relevance established only later
  5. 2005 High

    Established that C-terminal leucine-zipper homo-oligomerization is required for 14-3-3-mediated inhibition, linking quaternary structure to GEF regulation.

    Evidence Co-IP, leucine-zipper mutagenesis, Rho-GEF activity assays

    PMID:15691829

    Open questions at the time
    • Stoichiometry of oligomers not determined
    • No structural model of the oligomeric assembly
  6. 2007 High

    Placed AKAP13 downstream of α1-AR/Gα12 in driving cardiomyocyte hypertrophy and showed its GEF activity is required for TLR2-mediated NF-κB and cytokine responses, extending function to cardiac and innate-immune contexts.

    Evidence shRNA knockdown in cardiomyocytes with RhoA pulldowns; siRNA and GEF-deficient mutant in TLR2 reporter cells with NF-κB/cytokine readouts

    PMID:17537920 PMID:17878165

    Open questions at the time
    • Transcriptional mechanism of hypertrophy not yet resolved
    • TLR2 link rests on single lab
  7. 2008 High

    Connected AKAP13-coordinated PKD activation to HDAC5 nuclear export and MEF2 transcription, and identified its role in polarized leading-edge PKA gradients, linking scaffold function to gene reprogramming and migration.

    Evidence FRET kinase reporters, RNAi, nuclear export assays; FRET AKAR reporters with knockdown and PKA inhibition

    PMID:18951085 PMID:19106088

    Open questions at the time
    • Leading-edge gradient study is Medium confidence, single lab
    • In vivo cardiac requirement not yet tested
  8. 2009 High

    Identified LC3 as a direct N-terminal inhibitor of AKAP13 GEF activity, adding a third independent layer of GEF regulation.

    Evidence Co-IP, mutagenesis, Rho-GEF activity and actin stress fiber assays

    PMID:19696020

    Open questions at the time
    • Physiological/autophagic context of LC3 regulation unclear
    • Relationship to PKA/14-3-3 regulation not integrated
  9. 2010 High

    Demonstrated AKAP13 is essential for cardiac development via Gα12/Rho/MEF2C and scaffolds the KSR-1/RAF/MEK/ERK cassette, expanding its developmental and MAPK roles.

    Evidence Akap13-null mice with histology and MEF2C reporters; co-IP, kinase assays, and KSR-1 Ser838 mutagenesis

    PMID:20139090 PMID:21102438

    Open questions at the time
    • Tissue-specific developmental requirements not dissected
    • How RhoA-GEF and ERK scaffold outputs are coordinated unknown
  10. 2011 High

    Showed AKAP13 assembles a PKNα/MLTK/MKK3/p38α module downstream of α1b-AR and mediates integrin/LPA-driven RhoA activation for chemotaxis, defining selective MAPK and migration pathways.

    Evidence Co-IP, siRNA, p38 kinase assays; dominant-negative Rho, C3 transferase, GTPase pulldowns, chemotaxis assays

    PMID:21224381 PMID:22049212

    Open questions at the time
    • Integrin study Medium confidence, single lab
    • Crosstalk between RhoA and Rac1 activation incompletely mapped
  11. 2012 Medium

    Identified AKAP13-anchored PKA substrates Hsp20 (Ser16, cardioprotective) and Shp2 (inhibitory phosphorylation in hypertrophy), broadening its PKA effector repertoire.

    Evidence PKA anchoring disruptor peptides, co-IP, silencing/rescue, apoptosis and phosphatase activity assays in cardiac models

    PMID:22731613 PMID:23045525

    Open questions at the time
    • Both findings rest on single labs
    • Quantitative contribution to in vivo cardiac outcomes not established
  12. 2013 High

    Used domain-specific gene-trap mice to show the PKD-binding and GEF/PKD domains are dispensable for development but required for adaptive hypertrophy and contractility under stress, distinguishing developmental from stress-response functions.

    Evidence Gene-trap mice, transverse aortic constriction, neurohumoral infusion, HDAC5 phosphorylation, echocardiography

    PMID:23658642 PMID:24161911

    Open questions at the time
    • Mechanism of accelerated decompensation not fully resolved
    • GEF vs PKD domain contributions not cleanly separated
  13. 2014 High

    Solved the RhoA-GDP/DH-PH crystal structure, revealing a GEF-switch conformational change and a dispensable PH domain, providing the structural basis for nucleotide exchange.

    Evidence X-ray crystallography at 2.1 Å, nucleotide-exchange assays, ITC

    PMID:25186459

    Open questions at the time
    • No structure of regulatory/autoinhibited full-length protein
    • Structural basis of 14-3-3/LC3 inhibition unknown
  14. 2015 Medium

    Extended AKAP13 PKA-anchoring function to nuclear receptor signaling (ERα Ser305, tamoxifen resistance) and to osteogenesis (Runx2/ALP, bone density), demonstrating roles in cancer endocrinology and bone biology.

    Evidence Co-IP, FRET, siRNA, ERα phosphorylation/tamoxifen assays; Akap13 haploinsufficient mice with micro-CT and CFU-F assays

    PMID:25892096 PMID:26272591

    Open questions at the time
    • Both single-lab studies
    • Direct vs indirect contribution to transcription not fully resolved
  15. 2016 Medium

    Mapped a novel C-terminal Gα12-binding region conferring selectivity over Gα13, refining the receptor-coupling interface distinct from canonical RhoGEF RGS-homology domains.

    Evidence Co-IP, charge-reversal mutagenesis, chimeric Gα12/13 constructs, dominant-negative assays

    PMID:31051012

    Open questions at the time
    • No structure of the Gα12-binding interface
    • Single-lab finding
  16. 2017 Medium

    Showed AKAP13/PKD1 signaling mediates α1-AR cardioprotection against doxorubicin apoptosis via Bcl2/Bax regulation, linking the scaffold to cardiomyocyte survival.

    Evidence shRNA knockdown in cardiomyocytes, apoptosis and PKD1 activity assays, Bcl2/Bax expression/localization

    PMID:28923249

    Open questions at the time
    • Single-lab study
    • In vivo relevance of the protective axis not established
  17. 2019 Medium

    Identified PR-B as a direct AKAP13 partner with ligand-dependent, ERK-sensitive augmentation of activity, further linking the scaffold to nuclear receptor signaling.

    Evidence GST-binding assay, luciferase reporters, siRNA, ERK/p38 inhibition

    PMID:30239831

    Open questions at the time
    • GST pulldown without reciprocal in-cell validation
    • Mechanism of PR-A vs PR-B selectivity unknown
  18. 2021 Medium

    Established AKAP13 as an mTORC1-binding scaffold enabling PKA phosphorylation of Raptor (Ser791) to inhibit mTORC1, and as a CD47-coupled RhoA activator driving lymphoma metastasis, adding metabolic and oncogenic axes.

    Evidence Co-IP, Raptor phosphorylation, siRNA, proliferation/colony/tumor assays; CD47 co-IP, RhoA assays, metastasis assays

    PMID:33406263 PMID:34673774

    Open questions at the time
    • Both single-lab studies
    • How GEF and mTORC1-inhibitory functions are reconciled is unclear
  19. 2022 Medium

    Demonstrated AKAP13 scaffolds PKA toward CREB1 to amplify FSH-induced transcription in granulosa cells, extending its PKA-anchoring role to reproductive endocrine signaling.

    Evidence Co-IP, luciferase reporters, siRNA, CREB1 phosphorylation, qRT-PCR in granulosa cells

    PMID:36401072

    Open questions at the time
    • Single-lab study
    • In vivo reproductive phenotype not tested
  20. 2026 Medium

    Defined a FBXW7/AKAP13/YAP/chemokine axis in glioma and a P2Y14R/PKA/AKAP13/RhoA axis controlling neutrophil cytoskeletal rearrangement and NET release, connecting AKAP13 to tumor progression and thromboinflammation.

    Evidence siRNA in vitro/in vivo, YAP translocation and ubiquitination assays; neutrophil-specific P2Y14R knockout mice, phosphoproteomics, RhoA and NET assays

    PMID:41143464 PMID:41506544

    Open questions at the time
    • Both single-lab studies
    • Phosphosite controlling neutrophil RhoA inhibition not pinpointed to a defined residue

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple competing inputs (Gα12 activation, PKA/14-3-3 inhibition, oligomerization, LC3 binding, mTORC1 association, and FBXW7-mediated degradation) are integrated into a single regulated scaffold in a given cell type remains unresolved.
  • No structure of the autoinhibited full-length protein
  • No unified model of how scaffold outputs are temporally/spatially partitioned
  • Tissue-specific selection among effectors not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 3
Localization
GO:0005829 cytosol 2 GO:0005856 cytoskeleton 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1266738 Developmental Biology 2
Partners
CD47GNA12MAP1LC3PRKACAPRKD1RHOARPTORYWHAZ
Complex memberships
AKAP-Lbc PKA-signaling scaffoldKSR-1/RAF/MEK/ERK modulePKNα/MLTK/MKK3/p38α module

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 AKAP-Lbc (AKAP13) functions as both an A-kinase anchoring protein (AKAP) that binds PKA and a Rho-selective guanine nucleotide exchange factor (GEF). Expression in fibroblasts promotes stress fiber formation in a Rho-dependent manner, and Gα12 selectively couples to and activates AKAP-Lbc to drive RhoA signaling. Biochemical co-immunoprecipitation, overexpression in fibroblasts, stress fiber formation assay, selective Gα12 expression The Journal of biological chemistry High 11546812
2001 The Ht31/AKAP13 gene encodes AKAP13 and smaller splice variants (Brx and proto-Lbc); an endogenous ~309 kDa Ht31 protein co-immunoprecipitates RhoA from primary rat renal inner medullary collecting duct cells, confirming in vivo interaction between AKAP and RhoA. Protein detection by Western blot, co-immunoprecipitation from primary cells, cDNA cloning and sequencing FEBS letters Medium 11696353
2004 AKAP-Lbc assembles a protein kinase D (PKD) activation scaffold by recruiting upstream kinase PKCη and coordinating PKA phosphorylation events that release activated PKD, thereby synchronizing PKA and PKC activities to activate a third kinase. Biochemical co-immunoprecipitation, enzymatic kinase assays, immunofluorescence Molecular cell High 15383279
2004 PKA anchored to AKAP-Lbc phosphorylates AKAP-Lbc on Ser1565, which induces recruitment of 14-3-3, and 14-3-3 binding inhibits the Rho-GEF activity of AKAP-Lbc. Under basal conditions, 14-3-3 maintains AKAP-Lbc in an inactive state; AKAP-Lbc mutants that cannot bind PKA or 14-3-3 show elevated basal Rho-GEF activity. Co-immunoprecipitation, mutagenesis, cAMP elevation assays, Rho-GEF activity assays The EMBO journal High 15229649
2005 AKAP-Lbc forms homo-oligomers inside cells via two adjacent leucine zipper motifs in its C-terminal region. Disruption of oligomerization drastically increases basal RhoA-GEF activity. Additionally, 14-3-3 can only inhibit AKAP-Lbc Rho-GEF activity when the protein is in an oligomeric state; oligomerization-deficient mutants are resistant to PKA/14-3-3-mediated inhibition. Co-immunoprecipitation, leucine zipper mutagenesis, Rho-GEF activity assays The Journal of biological chemistry High 15691829
2007 AKAP-Lbc is critical for α1-adrenergic receptor (α1-AR)-mediated RhoA activation and cardiomyocyte hypertrophy. α1-ARs activate AKAP-Lbc via a Gα12-dependent pathway. shRNA suppression of AKAP-Lbc in neonatal ventricular cardiomyocytes strongly reduces α1-AR-mediated RhoA activation and hypertrophic responses. Lentiviral shRNA knockdown in primary cardiomyocytes, RhoA activation (Rhotekin pulldown) assays, hypertrophy morphological readouts Proceedings of the National Academy of Sciences of the United States of America High 17537920
2008 AKAP-Lbc is upregulated in hypertrophic cardiomyocytes and coordinates PKD activation coupled to phosphorylation-dependent nuclear export of class II histone deacetylase HDAC5, driving MEF2-mediated transcriptional reprogramming leading to pathological cardiac hypertrophy. Live-cell imaging, fluorescent kinase activity reporters (FRET), RNA interference, nuclear export assays Molecular cell High 18951085
2008 AKAP-Lbc is a major contributor to the formation of PKA activity gradients at the leading edge of migrating cells. FRET-based PKA activity reporters show strongest PKA activity at the leading edge (basal surface); disruption of PKA anchoring by Ht31 peptide or AKAP-Lbc knockdown abolishes this polarized gradient. FRET-based A-kinase activity reporter (AKAR1), immunocytochemistry with phospho-PKA substrate antibodies, RNAi knockdown, H-89/PKI inhibition The Journal of biological chemistry Medium 19106088
2009 The ubiquitin-like protein LC3 interacts with AKAP-Lbc via its N-terminal α-helical domain binding to two sites in the N-terminal regulatory region of AKAP-Lbc. LC3 overexpression reduces AKAP-Lbc interaction with RhoA, inhibits its Rho-GEF activity, and impairs actin stress fiber formation. AKAP-Lbc mutants that cannot bind LC3 display higher basal Rho-GEF activity and are refractory to LC3 inhibition. Co-immunoprecipitation, mutagenesis, Rho-GEF activity assays, actin stress fiber imaging The Journal of biological chemistry High 19696020
2010 AKAP13 (Brx-1/AKAP-Lbc) is essential for cardiac development in mice. Akap13-null embryos die at E10.5–11.0 with deficient sarcomere formation and thin-walled hearts. AKAP13 coordinates Gα12 and Rho signaling upstream of MEF2C transcription; Akap13 siRNA reduces Mef2c mRNA and AKAP13 overexpression augments MEF2C-dependent reporter activity. Akap13 knockout mouse, histology, siRNA knockdown, MEF2C reporter assays, qRT-PCR The Journal of biological chemistry High 20139090
2010 AKAP-Lbc forms the core of a signaling network with KSR-1 to relay signals from RAF through MEK to ERK1/2. AKAP-Lbc enhances ERK signaling by anchoring RAF near MEK1 and synchronizing PKA-mediated phosphorylation of Ser838 on KSR-1. Co-immunoprecipitation, kinase assays, mutational analysis, pharmacological inhibition Nature cell biology High 21102438
2011 AKAP-Lbc assembles a novel signaling complex containing PKNα, MLTK, MKK3, and p38α downstream of α1b-adrenergic receptors. This complex integrates α1b-AR signals to promote RhoA-dependent activation of p38α MAPK. Silencing AKAP-Lbc or disrupting the AKAP-Lbc·p38α complex specifically reduces α1-AR-mediated p38α activation without affecting other MAPK pathways. Co-immunoprecipitation, siRNA knockdown, p38 kinase activity assays, selective pathway inhibition The Journal of biological chemistry High 21224381
2011 Integrin α6β4 cooperates with LPA to activate RhoA specifically through AKAP-Lbc, and this RhoA activation is required for LPA-dependent chemotaxis and lamellae formation. AKAP-Lbc-mediated RhoA activation in turn facilitates Rac1 activation dependent on de novo β1 integrin ligation. Dominant-negative Rho constructs, C3 exotransferase, Rho kinase inhibitor, siRNA knockdown, GTPase pulldown assays, chemotaxis assays American journal of physiology. Cell physiology Medium 22049212
2012 AKAP-Lbc directly anchors PKA to facilitate phosphorylation of Hsp20 on Ser16, which is required for the anti-apoptotic cardioprotective actions of Hsp20. PKA anchoring disruptor peptides block this phosphorylation; gene silencing and rescue experiments confirm AKAP-Lbc is the responsible anchoring protein. PKA anchoring disruptor peptides, co-immunoprecipitation, immunofluorescence, gene silencing and rescue experiments, apoptosis assays The Biochemical journal Medium 22731613
2012 Shp2 (tyrosine phosphatase) is a component of the AKAP-Lbc complex; AKAP-Lbc-anchored PKA phosphorylates Shp2, inhibiting its phosphatase activity under pathological hypertrophic conditions in the heart (chronic β-adrenergic stimulation). Co-immunoprecipitation, phosphatase activity assays, cardiac hypertrophy models (chronic β-adrenergic stimulation) The Journal of biological chemistry Medium 23045525
2013 The C-terminus of AKAP-Lbc is critical for PKD1 interaction in vivo. AKAP-Lbc-ΔPKD mice (lacking PKD1-binding domain) show reduced PKD1 activation, diminished HDAC5 phosphorylation, and attenuated compensatory cardiac hypertrophy with accelerated progression to cardiac dysfunction under pressure overload or neurohumoral stimulation. Gene-trap mouse model, transverse aortic constriction (TAC), angiotensin/phenylephrine infusion, HDAC5 phosphorylation assays, echocardiography Journal of molecular and cellular cardiology High 24161911
2013 AKAP13 Rho-GEF and PKD-binding domains are not required for normal mouse development or cardiac architecture, but are required for proper cardiac contractility (fractional shortening and ejection fraction) in response to β-adrenergic-induced cardiac hypertrophy. Gene-trap mice lacking Rho-GEF and/or PKD-binding domains, isoproterenol stress, echocardiography, electrocardiograms PloS one Medium 23658642
2014 Crystal structure of the RhoA-GDP/AKAP-Lbc DH-PH domain complex was determined at 2.1 Å resolution. The PH domain plays no role in nucleotide exchange (confirmed by GEF assays comparing DH-PH vs. DH alone). The structure reveals a conformational change in the N-terminal 'GEF switch' region upon RhoA binding, and AKAP-Lbc has only micromolar affinity for RhoA (measured by ITC). X-ray crystallography (2.1 Å), nucleotide-exchange assays, isothermal titration calorimetry (ITC) The Biochemical journal High 25186459
2015 AKAP13 anchors PKA near estrogen receptor alpha (ERα) and a PKA regulatory subunit; AKAP13 knockdown prevents PKA-mediated phosphorylation of ERα on Ser305 and abrogates PKA-driven tamoxifen resistance in breast cancer cells. Co-immunoprecipitation, FRET analysis, siRNA knockdown, ERα Ser305 phosphorylation assays, tamoxifen resistance assays BMC cancer Medium 26272591
2015 Akap13 haploinsufficient mice display reduced bone mineral density, reduced osteoblast numbers, and diminished Runx2 and alkaline phosphatase expression, indicating AKAP13 is required for early osteogenesis. Akap13 siRNA knockdown in bone marrow stem cells reduces Runx2 and Alp transcripts. Akap13 haploinsufficient mice, micro-CT bone analysis, colony forming unit-fibroblast assays, siRNA knockdown in bone marrow stem cells, qRT-PCR Journal of bone and mineral research Medium 25892096
2016 A novel Gα12-binding region was identified near the C-terminus of AKAP-Lbc (distinct from the RGS-homology domain interface used by other RhoGEFs). AKAP-Lbc shows high selectivity for Gα12 over Gα13; charge-reversal of conserved residues in this region disrupts Gα12 binding. This binding region is also conserved in p114RhoGEF. Co-immunoprecipitation, mutagenesis (charge-reversal), chimeric Gα12/13 constructs, dominant-negative assays in cultured cells Journal of molecular signaling Medium 31051012
2017 AKAP-Lbc is required for α1-adrenergic receptor-mediated cardioprotection against doxorubicin-induced apoptosis. AKAP-Lbc mediates this protection through activation of anchored PKD1, which promotes Bcl2 expression and inhibits Bax translocation to mitochondria. Lentiviral shRNA knockdown in primary cardiomyocytes, apoptosis assays, PKD1 activity assays, Bcl2/Bax expression and localization Biochimica et biophysica acta. Molecular cell research Medium 28923249
2018 AKAP-Lbc-mediated RhoA activation controls aquaporin-2 (AQP2) trafficking in renal collecting duct principal cells. A small-molecule inhibitor (Scaff10-8) that binds RhoA and specifically blocks AKAP-Lbc-mediated (but not other GEF-mediated) RhoA activation promotes redistribution of AQP2 from intracellular vesicles to the plasma membrane. Small-molecule screen (18,431 compounds), focused library synthesis, RhoA activation assays, selectivity assays vs. Rac1/Cdc42, AQP2 localization in primary IMCD cells PloS one Medium 29373579
2019 AKAP13 physically interacts with progesterone receptor B (PR-B) through its carboxyl terminus (shown by GST-binding assay) and augments ligand-dependent PR-B (but not PR-A) activation. This effect is reduced by ERK inhibition but not p38 MAPK inhibition. GST-binding assay, luciferase reporter assay, siRNA knockdown, ERK/p38 inhibition The Journal of clinical endocrinology and metabolism Medium 30239831
2021 AKAP13 acts as a scaffold for PKA and mTORC1, enabling GPCR/Gαs/cAMP-induced PKA phosphorylation of Raptor on Ser791, thereby inhibiting mTORC1. AKAP13 was identified as an mTORC1 binding protein and mediates mTORC1-dependent cell proliferation, cell size, and colony formation. Co-immunoprecipitation identifying AKAP13-mTORC1 interaction, Raptor Ser791 phosphorylation assays, siRNA knockdown, cell proliferation and colony formation assays, in vivo lung tumor growth PLoS genetics Medium 34673774
2021 CD47 interacts with AKAP13 and facilitates AKAP13-mediated RhoA activation, promoting T-cell lymphoma metastasis through elevated basal RhoA activity independent of CD47's anti-phagocytic function. Co-immunoprecipitation, RhoA GTPase activation assays, siRNA knockdown, metastasis assays International immunology Medium 33406263
2022 AKAP13 physically interacts with CREB1 (shown by co-immunoprecipitation) and enhances FSH-induced PKA-dependent CREB1 phosphorylation in granulosa cells. AKAP13 siRNA knockdown reduces FSH-stimulated CREB1 phosphorylation and decreases aromatase and LH receptor transcript levels. Co-immunoprecipitation, luciferase reporter assays, siRNA knockdown, CREB1 phosphorylation assays, qRT-PCR in primary murine and COV434 granulosa cells Reproductive sciences Medium 36401072
2026 AKAP13 drives glioma progression by enhancing YAP expression and nuclear translocation, which upregulates TAM-recruiting chemokines CSF1 and CCL2. FBXW7 was identified as an upstream E3 ligase that promotes ubiquitin-mediated degradation of AKAP13, placing AKAP13 in a FBXW7/AKAP13/YAP/chemokine axis. siRNA knockdown in vitro and in vivo, YAP nuclear translocation assays, chemokine expression assays, ubiquitination assays Biochemical pharmacology Medium 41506544
2026 Neutrophil P2Y14 receptor deletion promotes PKA-induced phosphorylation of AKAP13, thereby inhibiting RhoA activation and cytoskeleton rearrangement, resulting in reduced neutrophil-platelet aggregates and NET release. This places AKAP13 in a PKA/AKAP13/RhoA signaling axis downstream of P2Y14R in neutrophils. Neutrophil-specific P2Y14R knockout mice, phosphoproteomics, immunofluorescence, RhoA activation assays, NET formation assays European heart journal Medium 41143464
2003 The HA-3 minor histocompatibility antigen peptide (VTEPGTAQY) is encoded by the AKAP13/Lbc oncogene. The allelic variant (VMEPGTAQY, HA-3M) is destroyed by proteasome-mediated digestion whereas the HA-3T peptide is not, explaining the differential immunogenicity — the Thr→Met substitution does not affect TAP transport or HLA-A1 binding but leads to proteasomal destruction of the negative allele. Mass spectrometry peptide identification, HLA binding assays, TAP transport assays, proteasome digestion assays, T-cell recognition assays Blood High 12663445
2007 AKAP13 (via its GEF activity) is required for TLR2-mediated NF-κB activation and IL-8/MCP-1 secretion in macrophages and epithelial cells. A GEF-deficient AKAP13 mutant partially inhibits NF-κB activation. AKAP13 is also involved in JNK phosphorylation but not ERK1/2 phosphorylation downstream of TLR2. siRNA knockdown in TLR2 reporter cell lines, GEF-deficient mutant expression, NF-κB reporter assay, cytokine ELISA, JNK/ERK phosphorylation assays The Journal of biological chemistry Medium 17878165

Source papers

Stage 0 corpus · 52 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 AKAP-Lbc anchors protein kinase A and nucleates Galpha 12-selective Rho-mediated stress fiber formation. The Journal of biological chemistry 208 11546812
2004 AKAP-Lbc nucleates a protein kinase D activation scaffold. Molecular cell 131 15383279
2008 AKAP-Lbc mobilizes a cardiac hypertrophy signaling pathway. Molecular cell 119 18951085
2010 New loci associated with central cornea thickness include COL5A1, AKAP13 and AVGR8. Human molecular genetics 112 20719862
2010 AKAP-Lbc enhances cyclic AMP control of the ERK1/2 cascade. Nature cell biology 108 21102438
2004 Anchoring of both PKA and 14-3-3 inhibits the Rho-GEF activity of the AKAP-Lbc signaling complex. The EMBO journal 108 15229649
2007 The A-kinase anchoring protein (AKAP)-Lbc-signaling complex mediates alpha1 adrenergic receptor-induced cardiomyocyte hypertrophy. Proceedings of the National Academy of Sciences of the United States of America 89 17537920
2003 The minor histocompatibility antigen HA-3 arises from differential proteasome-mediated cleavage of the lymphoid blast crisis (Lbc) oncoprotein. Blood 82 12663445
2005 Leucine zipper-mediated homo-oligomerization regulates the Rho-GEF activity of AKAP-Lbc. The Journal of biological chemistry 65 15691829
2010 The Rho guanine nucleotide exchange factor AKAP13 (BRX) is essential for cardiac development in mice. The Journal of biological chemistry 60 20139090
2001 Ht31: the first protein kinase A anchoring protein to integrate protein kinase A and Rho signaling. FEBS letters 56 11696353
2007 AKAP13, a RhoA GTPase-specific guanine exchange factor, is a novel regulator of TLR2 signaling. The Journal of biological chemistry 52 17878165
2011 A-kinase anchoring protein (AKAP)-Lbc anchors a PKN-based signaling complex involved in α1-adrenergic receptor-induced p38 activation. The Journal of biological chemistry 49 21224381
2008 Spatial distribution of protein kinase A activity during cell migration is mediated by A-kinase anchoring protein AKAP Lbc. The Journal of biological chemistry 47 19106088
2012 The A-kinase-anchoring protein AKAP-Lbc facilitates cardioprotective PKA phosphorylation of Hsp20 on Ser(16). The Biochemical journal 39 22731613
2011 Integrin α6β4 cooperates with LPA signaling to stimulate Rac through AKAP-Lbc-mediated RhoA activation. American journal of physiology. Cell physiology 36 22049212
2006 AKAP-Lbc: a molecular scaffold for the integration of cyclic AMP and Rho transduction pathways. European journal of cell biology 36 16460837
2010 The significance of 2-furyl ring substitution with a 2-(para-substituted) aryl group in a new series of pyrazolo-triazolo-pyrimidines as potent and highly selective hA(3) adenosine receptors antagonists: new insights into structure-affinity relationship and receptor-antagonist recognition. Journal of medicinal chemistry 35 20307065
2013 The C-terminus of the long AKAP13 isoform (AKAP-Lbc) is critical for development of compensatory cardiac hypertrophy. Journal of molecular and cellular cardiology 33 24161911
2005 Association of genetic variants in the Rho guanine nucleotide exchange factor AKAP13 with familial breast cancer. Carcinogenesis 32 16234258
2014 The crystal structure of the RhoA-AKAP-Lbc DH-PH domain complex. The Biochemical journal 29 25186459
2010 Ht31, a protein kinase A anchoring inhibitor, induces robust cholesterol efflux and reverses macrophage foam cell formation through ATP-binding cassette transporter A1. The Journal of biological chemistry 26 21106522
2018 An AKAP-Lbc-RhoA interaction inhibitor promotes the translocation of aquaporin-2 to the plasma membrane of renal collecting duct principal cells. PloS one 25 29373579
2011 Amplification of thymosin beta 10 and AKAP13 genes in metastatic and aggressive papillary thyroid carcinomas. Pathology oncology research : POR 25 22161024
2019 A-Kinase Anchoring Protein 13 (AKAP13) Augments Progesterone Signaling in Uterine Fibroid Cells. The Journal of clinical endocrinology and metabolism 23 30239831
2012 AKAP13, CACNA1, GRIK4 and GRIA1 genetic variations may be associated with haloperidol efficacy during acute treatment. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 22 22980146
2009 The ubiquitin-like protein LC3 regulates the Rho-GEF activity of AKAP-Lbc. The Journal of biological chemistry 21 19696020
2021 AKAP13 couples GPCR signaling to mTORC1 inhibition. PLoS genetics 19 34673774
2015 Protein Kinase A-induced tamoxifen resistance is mediated by anchoring protein AKAP13. BMC cancer 19 26272591
2021 MiR-629-5p Promotes Prostate Cancer Development and Metastasis by Targeting AKAP13. Frontiers in oncology 18 34722307
2012 Src homology 2 domain-containing phosphatase 2 (Shp2) is a component of the A-kinase-anchoring protein (AKAP)-Lbc complex and is inhibited by protein kinase A (PKA) under pathological hypertrophic conditions in the heart. The Journal of biological chemistry 18 23045525
2017 AKAP-Lbc mediates protection against doxorubicin-induced cardiomyocyte toxicity. Biochimica et biophysica acta. Molecular cell research 16 28923249
2015 Mice Deficient in AKAP13 (BRX) Are Osteoporotic and Have Impaired Osteogenesis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 16 25892096
2014 Ht31 peptide inhibited inflammatory pain by blocking NMDA receptor-mediated nociceptive transmission in spinal dorsal horn of mice. Neuropharmacology 15 25312281
2011 A regulatory SNP in AKAP13 is associated with blood pressure in Koreans. Journal of human genetics 15 21228793
2006 AKAPs competing peptide HT31 disrupts the inhibitory effect of PKA on RhoA activity. Oncology reports 14 16969490
2019 Structure-Based Optimization of Coumarin hA3 Adenosine Receptor Antagonists. Journal of medicinal chemistry 12 31738058
2020 Long Non-Coding RNA ZNF667-AS1 Knockdown Curbs Liver Metastasis in Acute Myeloid Leukemia by Regulating the microRNA-206/AKAP13 Axis. Cancer management and research 11 33380835
2013 AKAP13 Rho-GEF and PKD-binding domain deficient mice develop normally but have an abnormal response to β-adrenergic-induced cardiac hypertrophy. PloS one 11 23658642
2021 CD47 promotes T-cell lymphoma metastasis by up-regulating AKAP13-mediated RhoA activation. International immunology 10 33406263
2016 A Gα12-specific Binding Domain in AKAP-Lbc and p114RhoGEF. Journal of molecular signaling 10 31051012
2018 Mice deficient in AKAP13 (BRX) develop compulsive-like behavior and increased body weight. Brain research bulletin 8 29653158
1996 Physical mapping of the Borrelia miyamotoi HT31 chromosome in comparison with that of Borrelia turicatae, an etiological agent of tick-borne relapsing fever. Clinical and diagnostic laboratory immunology 7 8877131
2021 A deletion mutation within the goat AKAP13 gene is significantly associated with litter size. Animal biotechnology 6 34431749
2026 Targeting P2Y14R alleviates platelet-induced NET formation and venous thrombosis through PKA/AKAP13/RhoA axis. European heart journal 4 41143464
2023 InDel and CNV within the AKAP13 Gene Revealing Strong Associations with Growth Traits in Goat. Animals : an open access journal from MDPI 4 37685010
2016 The in silico identification of small molecules for protein-protein interaction inhibition in AKAP-Lbc-RhoA signaling complex. Computational biology and chemistry 4 28063348
2022 Design, Synthesis and Biological Evaluation of 1,3,5-Triazine Derivatives Targeting hA1 and hA3 Adenosine Receptor. Molecules (Basel, Switzerland) 2 35807265
2022 AKAP13 Enhances CREB1 Activation by FSH in Granulosa Cells. Reproductive sciences (Thousand Oaks, Calif.) 2 36401072
2009 Resonance assignments of the human AKAP13-PH domain and stabilizing DH helix. Biomolecular NMR assignments 2 19888694
2026 Targeting the FBXW7-AKAP13-YAP axis suppresses gliomagenesis by dual inhibition of tumor invasion and macrophage recruitment. Biochemical pharmacology 1 41506544
2023 Long Non-Coding RNA ZNF667-AS1 Knockdown Curbs Liver Metastasis in Acute Myeloid Leukemia by Regulating the microRNA-206/AKAP13 Axis [Retraction]. Cancer management and research 0 37953887

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