Wave2 activates serum response element via its VCA region and functions downstream of Rac

WAVE2 is a member of the WASP/WAVE family of protein effectors of actin reorganization and cell movement. In this report, we demonstrate that WAVE2 overexpression induces serum response element (SRE) activation through serum response factor. A WAVE2 mutant lacking the VCA region did not induce SIZE activation and actin polymerization. WAVE2-induced SRE activation was blocked by exposure of cells to Latrunculin A, or overexpression of actin mutant R62D. The DeltaVCA mutant inhibited Rae V12-induced SRE activation, suggesting that WAVE2 lies downstream of Rac. Similar deletion of the VCA domain of WASP attenuated Cdc42 V12-mediated SIZE activation, suggesting that WAVE2 acts in relation to Rae as WASP acts in relation to Cdc42. WAVE2 overexpression did not activate NF-kappaB. (C) 2004 Elsevier Inc. All rights reserved.