The guanine nucleotide exchange factor p63RhoGEF, a specific link between Gq/11-coupled receptor signaling and RhoA

The monomeric GTPase RhoA, which is a key regulator of numerous cellular processes, is activated by a variety of G protein-coupled receptors, through either G(12) or Gq family proteins. Here we report that p63RhoGEF, a recently identified RhoA-specific guanine nucleotide exchange factor, enhances the Rho-dependent gene transcription induced by agonist-stimulated G(q/11)- coupled receptors ( M-3-cholinoceptor, histamine H-1 receptor) or GTPase-deficient mutants of G alpha(q) and G(alpha 11). We further demonstrate that active G(alpha q) or G(alpha 11), but not G(alpha 12) or G(alpha 13), strongly enhances p63RhoGEF- induced RhoA activation by direct protein-protein interaction with p63RhoGEF at its C-terminal half. Moreover, the activation of p63RhoGEF by G(alpha q/11) occurs independently of and in competition to the activation of the canonical G(alpha q/11) effector phospholipase C beta. Therefore, our results elucidate a new signaling pathway by which G(q/11)- coupled receptors specifically induce Rho signaling through a direct interaction of activated G(alpha q/11) subunits with p63RhoGEF.