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

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  • Arthur, William T.
    • Affiliation: School of Medicine, Department of Cell Biology and Physiology
  • Petch, Leslie A
    • Affiliation: School of Medicine, Department of Cell Biology and Physiology
  • Burridge, Keith
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
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. 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, 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. Transient suppression of RhoA by integrins may alleviate contractile forces that would otherwise impede protrusion at the leading edge of migrating cells.
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  • Journal Item
Rights statement
  • In Copyright
Journal title
  • Current Biology
Journal volume
  • 10
Journal issue
  • 12
Page start
  • 719
Page end
  • 722
Language
  • English
Version
  • Postprint
ISSN
  • 0960-9822

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