Activators of G proteins inhibit GSK-3beta and stabilize beta-Catenin in Xenopus oocytes.
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 Wnt signaling has been proposed. Here I have used Xenopus oocytes to study the role of heterotrimeric G proteins in the regulation of GSK-3beta and beta-Catenin, two essential components of the canonical Wnt pathway. In these cells, general activators of G proteins such as GTPgamma-S and AlF4(-) increase beta-Catenin stability and decrease GSK-3beta mediated phosphorylation of the microtubule associated protein, Tau. Among several members of Galpha proteins tested, expression of a constitutively active mutant of Galphaq (GalphaqQL) led to a significant increase in accumulation of beta-Catenin. The stabilization of beta-Catenin mediated by Galphaq was reversed by a Galphaq specific inhibitor, Gp-antagonist 2A, but not by a specific blocking peptide for Galphas. Expression of GalphaqQL also inhibited GSK-3beta-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.
Najafi
S Mahmoud A
SM
Department of Cell & Molecular Biology, School of Biology, University College of Science, University of Tehran, Tehran, Iran. najafim@khayam.ut.ac.ir
D000818:Animals; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D000071679:Glycogen Synthase Kinase 3 beta; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006801:Humans; D009865:Oocytes; D055550:Protein Stability; D014982:Xenopus laevis; D051176:beta Catenin / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
D051176:beta Catenin; D016875:tau Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D043802:GTP-Binding Protein alpha Subunits, Gq-G11