The Guanine Nucleotide Exchange Factor p63RhoGEF, a Specific Link between G sub(q/11)-coupled Receptor Signaling and RhoA

• Published in: The Journal of biological chemistry 2005-03, Vol.280 (12), p.11134-11139
• Main Authors: Lutz, Susanne, Freichel-Blomquist, Andrea, Yang, Yang, Rumenapp, Ulrich, Jakobs, Karl H, Schmidt, Martina, Wieland, Thomas
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X

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 sub(12) or G sub(q) 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 sub(q/11)- coupled receptors (M sub(3)-cholinoceptor, histamine H sub(1) receptor) or GTPase- deficient mutants of Galpha sub(q) and Galpha sub(11). We further demonstrate that active Galpha sub(q) or Galpha sub(11), but not Galpha sub(12) or Galpha sub(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 Galpha sub(q/11) occurs independently of and in competition to the activation of the canonical Galpha sub(q/11) effector phospholipase C beta . Therefore, our results elucidate a new signaling pathway by which Galpha sub(q/11)-coupled receptors specifically induce Rho signaling through a direct interaction of activated Galpha sub(q/11) subunits with p63RhoGEF.