title: Wnt3a-stimulated LRP6 phosphorylation is dependent upon arginine methylation of G3BP2.
abstract: Wnt signaling is initiated upon binding of Wnt proteins to Frizzled proteins and their co-receptors LRP5 and 6. The signal is then propagated to several downstream effectors, mediated by the phosphoprotein scaffold, dishevelled. We report a novel role for arginine methylation in regulating Wnt3a-stimulated LRP6 phosphorylation. G3BP2, a dishevelled-associated protein, is methylated in response to Wnt3a. The Wnt3a-induced LRP6 phosphorylation is attenuated by G3BP2 knockdown, chemical inhibition of methyl transferase activity or expression of methylation-deficient mutants of G3BP2. Arginine methylation of G3BP2 appears to be a Wnt3a-sensitive 'switch' regulating LRP6 phosphorylation and canonical Wnt-β-catenin signaling.
authors.affiliation: Department of Pharmacology, School of Medicine, Health Sciences Center, State University of New York at Stony Brook, Stony Brook, NY 11794-8651, USA. kamesh.bikkavilli@ucdenver.edu
authors.forename: Rama Kamesh
authors.initials: RK
authors.lastname: Bikkavilli
authors.forename: Craig C
authors.initials: CC
authors.lastname: Malbon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000235:genetics / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D016601:RNA-Binding Proteins; D015398:Signal Transduction; D015854:Up-Regulation; D060509:Wnt3A Protein / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C574606:G3BP2 protein, human; C576524:G3BP2 protein, mouse; D060488:Low Density Lipoprotein Receptor-Related Protein-6; C555476:Lrp6 protein, mouse; D016601:RNA-Binding Proteins; D060509:Wnt3A Protein; D051176:beta Catenin; D020703:ras GTPase-Activating Proteins; D001120:Arginine