Induction of membrane circular dorsal ruffles requires co-signalling of integrin-ILK-complex and EGF receptor.

Abstract:

:Integrin and receptor tyrosine kinase signalling networks cooperate to regulate various biological functions. The molecular details underlying the integration of both signalling networks remain largely uncharacterized. Here we identify a signalling module composed of a fibronectin-α5β1-integrin-integrin-linked-kinase (ILK) complex that, in concert with epidermal growth factor (EGF) cues, cooperatively controls the formation of transient actin-based circular dorsal ruffles (DRs) in fibroblasts. DR formation depends on the precise spatial activation of Src at focal adhesions by integrin and EGF receptor signals, in an ILK-dependent manner. In a SILAC-based phosphoproteomics screen we identified the tumour-suppressor Cyld as being required for DR formation induced by α5β1 integrin and EGF receptor co-signalling. Furthermore, EGF-induced Cyld tyrosine phosphorylation is controlled by integrin-ILK and Src as a prerequisite for DR formation. This study provides evidence for a novel function of integrin-ILK and EGF signalling crosstalk in mediating Cyld tyrosine phosphorylation and fast actin-based cytoskeletal rearrangements.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Azimifar SB,Böttcher RT,Zanivan S,Grashoff C,Krüger M,Legate KR,Mann M,Fässler R

doi

10.1242/jcs.091652

subject

Has Abstract

pub_date

2012-01-15 00:00:00

pages

435-48

issue

Pt 2

eissn

0021-9533

issn

1477-9137

pii

jcs.091652

journal_volume

125

pub_type

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