title: Integrin engagement suppresses RhoA activity via a c-Src-dependent mechanism.
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] [4] [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] [7] [8]. Transient suppression of RhoA by integrins may alleviate contractile forces that would otherwise impede protrusion at the leading edge of migrating cells.
authors.affiliation: Department of Cell Biology and Anatomy, University of North Carolina, Chapel Hill 27599, USA. william_t_arthur@med.unc.edu
authors.forename: W T
authors.initials: WT
authors.lastname: Arthur
authors.forename: L A
authors.initials: LA
authors.lastname: Petch
authors.forename: K
authors.initials: K
authors.lastname: Burridge
mesh_terms: D020690:GTPase-Activating Proteins / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D020690:GTPase-Activating Proteins; D016023:Integrins; D016392:Proto-Oncogene Proteins pp60(c-src); D020742:rhoA GTP-Binding Protein