Activation of RhoA by association of G alpha(13) with Dbl

RhoA is a small G protein that is implicated in the regulation of the actin cytoskeleton, gene expression, and cell cycle progression, It is activated by many agonists whose receptors are linked to heterotrimeric G proteins, but the mechanisms are incompletely understood. In this study, we show that the constitutively active alpha -subunit of the heterotrimeric G protein G (13) associated with the Rho family guanine nucleotide exchange factor Dbl in NIH 3T3 cells and that this resulted in activation of RhoA. This activat ion was not seen with wild-type G alpha (13) if Dbl and active G alpha (13) were expressed separately and mixed. In contrast, coexpression of constitu tively active G alpha (q) With Dbl did not lead to their association and ca used a weak activation of RhoA that was no greater than that observed with wild-type G alpha (q). These findings illustrate that activated G alpha (13 ) and Dbl can associate in vivo and that this leads to Rho activation. (C) 2000 Academic Press.