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

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 filopod ia. RhoA regulates contractility and assembly of actin stress fibers and fo cal 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 Rh oA, in a c-Src-dependent manner, but has no effect on Cdc42 or Rac1 activit y. Additionally, early integrin signaling induces activation and tyrosine p hosphorylation of p190RhoGAP via a mechanism that requires c-Src. Dynamic m odulation of RhoA activity appears to have a role in motility, as both inhi bition 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. (C) 2000 Elsevie r Science Ltd. All rights reserved.