Integrin engagement suppresses RhoA activity via a c-Src-dependent mechanism

William T. Arthur, Leslie Anne Petch Lee, Keith Burridge

Research output: Contribution to journalArticle

357 Citations (Scopus)

Abstract

The Rho family GTPases Cdc42, Rac1 and RhoA control many of the changes in the actin cytoskeleton that are triggered when growth factor receptors and integrins bind their ligands [1,2]. Rac1 and Cdc42 stimulate the formation of protrusive structures such as membrane ruffles, lamellipodia and filopodia. RhoA regulates contractility and assembly of actin stress fibers and focal adhesions. Although prolonged integrin engagement can stimulate RhoA [3-5], regulation of this GTPase by early integrin-mediated signals is poorly understood. Here we show that integrin engagement initially inactivates RhoA, in a c-Src-dependent manner, but has no effect on Cdc42 or Rac1 activity. Additionally, early integrin signaling induces activation and tyrosine phosphorylation of p190RhoGAP via a mechanism that requires c-Src. Dynamic modulation of RhoA activity appears to have a role in motility, as both inhibition and activation of RhoA hinder migration [6-8]. Transient suppression of RhoA by integrins may alleviate contractile forces that would otherwise impede protrusion at the leading edge of migrating cells.

Original languageEnglish (US)
Pages (from-to)719-722
Number of pages4
JournalCurrent Biology
Volume10
Issue number12
DOIs
StatePublished - Jun 1 2000

Fingerprint

integrins
Integrins
pseudopodia
Pseudopodia
GTP Phosphohydrolases
guanosinetriphosphatase
Actins
Chemical activation
Stress Fibers
rho GTP-Binding Proteins
Phosphorylation
Focal Adhesions
Growth Factor Receptors
microfilaments
Actin Cytoskeleton
growth factors
actin
Tyrosine
adhesion
tyrosine

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Integrin engagement suppresses RhoA activity via a c-Src-dependent mechanism. / Arthur, William T.; Petch Lee, Leslie Anne; Burridge, Keith.

In: Current Biology, Vol. 10, No. 12, 01.06.2000, p. 719-722.

Research output: Contribution to journalArticle

Arthur, William T. ; Petch Lee, Leslie Anne ; Burridge, Keith. / Integrin engagement suppresses RhoA activity via a c-Src-dependent mechanism. In: Current Biology. 2000 ; Vol. 10, No. 12. pp. 719-722.
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