title: Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly.
abstract: The adenomatous polyposis coli gene (APC) is mutated in most colon cancers. The APC protein binds to the cellular adhesion molecule beta-catenin, which is a mammalian homolog of ARMADILLO, a component of the WINGLESS signaling pathway in Drosophila development. Here it is shown that when beta-catenin is present in excess, APC binds to another component of the WINGLESS pathway, glycogen synthase kinase 3beta (GSK3beta), a mammalian homolog of Drosophila ZESTE WHITE 3. APC was a good substrate for GSK3 beta in vitro, and the phosphorylation sites were mapped to the central region of APC. Binding of beta-catenin to this region was dependent on phosphorylation by GSK3 beta.
authors.affiliation: Onyx Pharmaceuticals, Richmond, CA 94806, USA.
authors.forename: B
authors.initials: B
authors.lastname: Rubinfeld
authors.forename: I
authors.initials: I
authors.lastname: Albert
authors.forename: E
authors.initials: E
authors.lastname: Porfiri
authors.forename: C
authors.initials: C
authors.lastname: Fiol
authors.forename: S
authors.initials: S
authors.lastname: Munemitsu
authors.forename: P
authors.initials: P
authors.lastname: Polakis
mesh_terms: D025601:Adenomatous Polyposis Coli Protein; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006801:Humans; D051379:Mice; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D051176:beta Catenin
chemical_list: D025601:Adenomatous Polyposis Coli Protein; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3