AKAP2

Last update 08 May 2025

Basic Info

Synonyms

A-kinase anchor protein 2, A-kinase anchoring protein 2, AKAP-2

+ [7]

Introduction

Binds to regulatory subunit (RII) of protein kinase A. May be involved in establishing polarity in signaling systems or in integrating PKA-RII isoforms with downstream effectors to capture, amplify and focus diffuse, trans-cellular signals carried by cAMP. Binds to and modulates the structure of the actin cytoskeleton.

100 Clinical Results associated with AKAP2

100 Translational Medicine associated with AKAP2

0 Patents (Medical) associated with AKAP2

Literatures (Medical) associated with AKAP2

01 Dec 2024·Alzheimer's & Dementia

Multi‐ancestry genome‐wide gene × age interaction study identifies novel loci associated with late‐onset Alzheimer’s Disease

Article

Author: Martin, Eden R ; Haines, Jonathan L ; Bush, William S ; Wang, Li-San ; Zhang, Xiaoling ; Lunetta, Kathryn L ; Pericak-Vance, Margaret A ; Tong, Tong ; Schellenberg, Gerard D ; Farrer, Lindsay A ; Farrell, John J ; Zhu, Congcong

AbstractBackgroundAge is the largest risk factor for late‐onset Alzheimer’s Disease (LOAD). Although >80 genetic loci have been associated with LOAD, little is known about the age dependencies of these associations except the APOE region.MethodWe performed cross‐ancestry and ancestry‐specific genome‐wide gene‐age interaction and age‐stratified association study using TOPMed‐imputed genome‐wide association study (GWAS) data from Alzheimer’s Disease Genetics Consortium (ADGC) including 34,833 non‐Hispanic Whites (NHW), 7,264 African Americans (AA), 3,232 East Asians (EA), and 2,024 Caribbean Hispanics (CH) aged 60 years and older. We chose an approximate median age‐at‐onset threshold of 75 to dichotomize participants into younger (Ncase:Ncontrol = 10, 905:11,624) and older (Ncase:Ncontrol = 9,982:14,842) groups. We first evaluated the association of LOAD with the interaction of SNP × age within each cohort using a linear mixed‐effect model including a binary term for the age group, numeric age, sex, and the first 5 principal components (PCs) of ancestry. Results from each cohort were combined using a fixed‐effect model to jointly estimate the regression coefficients of SNP and SNP × age terms, both within‐ancestry and cross‐ancestry analyses. We also performed an age‐stratified analysis that included all controls regardless of age to increase power and using the same linear model without the interaction term. Results across cohorts were combined by meta‐analysis using a fixed‐effect model within‐ancestry and a modified random‐effect model across ancestry.ResultIn cross‐ancestry joint meta‐analysis, we identified 6 genome‐wide significant (GWS) loci, 4 of which showed nominal evidence of age‐dependent association with LOAD, including CD2AP (rs5876027, PJoint = 2.33 × 10‐8, PSNP×age = 0.043), PICALM (rs583162, PJoint = 2.34 × 10‐8, PSNP×age = 7.60 × 10‐3), APOE (rs429358, PJoint = 0, PSNP×age = 1.58 × 10‐7) and LILRA5 (rs1761461, PJoint = 4.86 × 10‐8, PSNP×age = 0.032), for the first time. Within‐ancestry joint meta‐analysis identified novel associations with VXN (rs146432976, PJoint = 2.29 × 10‐8, PSNP×age = 3.08 × 10‐5) in AAs and PALM2‐AKAP2 (rs67191673, PJoint = 3.46 × 10‐9, PSNP×age = 0.013) in EAs. CR1 (rs6661489, PJoint = 3.54 × 10‐8) and TREM2 (rs75932628, PJoint = 8.61 × 10‐10) were associated with LOAD in NHWs but showed no evidence of age‐dependent effects. In cross‐ancestry age‐stratified GWAS, BIN1, PICALM, and APOE region genes reached GWS in both strata, while MS4A6A was only significant in older group (rs7232, OR = 0.88, P = 4.23 × 10‐8). A GWS association with PALM2‐AKAP2 (rs67191673, OR = 1.94, P = 3.64 × 10‐9) was identified in the EA younger group.ConclusionWe identified several ancestry‐specific age‐dependent association with previously established and novel loci.

01 Aug 2024·Cell Reports

Proteomic analysis reveals a PLK1-dependent G2/M degradation program and a role for AKAP2 in coordinating the mitotic cytoskeleton

Article

Author: Mouery, Ryan D ; Robertson, Kevin C ; Herring, Laura E ; Hsu, Carolyn ; Bonacci, Thomas ; Branigan, Timothy B ; Toomer, E Drew ; Lukasik, Kimberly ; Canterbury, Owen G ; Gupton, Stephanie L ; Emanuele, Michael J ; Brown, Nicholas G ; Bolhuis, Derek L ; Mills, C Allie ; Wang, Xianxi

Ubiquitination is an essential regulator of cell division. The kinase Polo-like kinase 1 (PLK1) promotes protein degradation at G2/M phase through the E3 ubiquitin ligase Skp1-Cul1-F box (SCF)^βTrCP. However, the magnitude to which PLK1 shapes the mitotic proteome is uncharacterized. Combining quantitative proteomics with pharmacologic PLK1 inhibition revealed a widespread, PLK1-dependent program of protein breakdown at G2/M. We validated many PLK1-regulated proteins, including substrates of the cell-cycle E3 SCF^{Cyclin F}, demonstrating that PLK1 promotes proteolysis through at least two distinct E3 ligases. We show that the protein-kinase-A-anchoring protein A-kinase anchor protein 2 (AKAP2) is cell-cycle regulated and that its mitotic degradation is dependent on the PLK1/βTrCP signaling axis. Expression of a non-degradable AKAP2 mutant resulted in actin defects and aberrant mitotic spindles, suggesting that AKAP2 degradation coordinates cytoskeletal organization during mitosis. These findings uncover PLK1's far-reaching role in shaping the mitotic proteome post-translationally and have potential implications in malignancies where PLK1 is upregulated.

01 Mar 2024·Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

AKAP2-anchored extracellular signal-regulated kinase 1 (ERK1) regulates cardiac myofibroblast migration

Article

Author: Diviani, Dario ; Gautschi, Ivan ; Scherler, Greta ; Paterek, Aleksandra ; Delaunay, Marion

Cardiac fibrosis is a major cause of dysfunctions and arrhythmias in failing hearts. At the cellular level fibrosis is mediated by cardiac myofibroblasts, which display an increased migratory capacity and secrete large amounts of extracellular matrix. These properties allow myofibroblasts to invade, remodel and stiffen the myocardium and eventually alter cardiac function. While the enhanced ability of cardiac myofibroblasts to migrate has been proposed to contribute to the initiation of the fibrotic process, the molecular mechanisms controlling their motile function have been poorly defined. In this context, our current findings indicate that A-kinase anchoring protein 2 (AKAP2) associates with actin at the leading edge of migrating cardiac myofibroblasts. Proteomic analysis of the AKAP2 interactome revealed that this anchoring protein assembles a signaling complex composed of the extracellular regulated kinase 1 (ERK1) and its upstream activator Grb2 that mediates the activation of ERK in cardiac myofibroblasts. Silencing AKAP2 expression results in a significant reduction in the phosphorylation of ERK1 and its downstream effector WAVE2, a protein involved in actin polymerization, and impairs the ability of cardiac myofibroblasts to migrate. Importantly, disruption of the interaction between AKAP2 and F-actin using cell-permeant competitor peptides, inhibits the activation of the ERK-WAVE2 signaling axis, resulting in a reduction of the translocation of Arp2 to the leading-edge membrane and in inhibition of cardiac myofibroblast migration. Collectively, these findings suggest that AKAP2 functions as an F-actin bound molecular scaffold mediating the activation of an ERK1-dependent promigratory transduction pathway in cardiac myofibroblasts.

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AKAP2

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