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

Details

Serval ID
serval:BIB_01997C96805D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
AKAP2-anchored extracellular signal-regulated kinase 1 (ERK1) regulates cardiac myofibroblast migration.
Journal
Biochimica et biophysica acta. Molecular cell research
Author(s)
Delaunay M., Paterek A., Gautschi I., Scherler G., Diviani D.
ISSN
1879-2596 (Electronic)
ISSN-L
0167-4889
Publication state
In Press
Peer-reviewed
Oui
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
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.
Keywords
A kinase anchoring protein (AKAP), Cardiac fibrosis, Cardiac remodeling, Cell migration, Kinases
Pubmed
Open Access
Yes
Create date
26/01/2024 13:21
Last modification date
27/01/2024 7:38
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