Frizzled proteins, the receptors for Wnt ligands have seven hydrophobic transmembrane domains, a Structural feature of G protein coupled receptors. Therefore a role for G proteins in the regulation of Writ signaling has been proposed. Here I have used Xenopus oocytes to Study the role of heterotrimeric G proteins in the regulation of GSK-3 beta and beta-Catenin, two essential components of the canonical Writ pathway. In these cells, general activators of G proteins such as GTP gamma-S and AIF4(-) increase P-Catenin stability and decrease GSK-3 beta mediated phosphorylation of the microtubule associated protein, Tau. Among several members of Got proteins tested, expression of a constitutively active mutant of G alpha q (G alpha qQL) led to a significant increase in accumulation of P-Catenin. The stabilization of P-Catenin mediated by G alpha q was reversed by a G alpha q specific inhibitor, Gp-antagonist 2A, but not by a specific blocking peptide for Gas. Expression of G alpha qQL also inhibited GSK-3 beta-mediated tau phosphorylation in Xenopus oocytes. These results support a role for the Gq class of G proteins in the regulation of Wnt/beta-Catenin signal transduction. (C) 2009 Elsevier Inc. All rights reserved.