A mode of regulation of beta-catenin signaling activity in Xenopus embryos independent of its levels.
The signaling activity of beta-catenin is thought to be regulated by phosphorylation of a cluster of N-terminal serines, putative sites for GSK3beta. In the prevailing model in the literature, GSK3beta-dependent phosphorylation of these sites targets beta-catenin for ubiquitin-mediated degradation. Wnt signaling inhibits GSK3beta activity and this blocks degradation, allowing beta-catenin to accumulate and signal. We show here that beta-catenin activity is not regulated solely by protein stability. Mutations in the putative GSK3beta phosphorylation sites of beta-catenin enhance its signaling activity, but this cannot be accounted for by accumulation of either total or cadherin-free protein. Instead, the mutant protein has a threefold higher specific activity than the wild type both in vivo and in an in vitro signaling assay. We conclude that the N-terminal serines convey a layer of regulation upon beta-catenin signaling in addition to the effects these sites exert upon protein stability.
Guger
K A
KA
Cellular Biochemistry and Biophysics, Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, USA.
Gumbiner
B M
BM
D000595:Amino Acid Sequence; D000818:Animals; D001224:Aspartic Acid / Q000235:genetics; D019521:Body Patterning; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism*; D008845:Microinjections; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012694:Serine / Q000235:genetics; D015398:Signal Transduction; D015534:Trans-Activators; D014981:Xenopus; D029867:Xenopus Proteins; D051176:beta Catenin
C495266:CTNNB1 protein, Xenopus; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D029867:Xenopus Proteins; D051176:beta Catenin; D001224:Aspartic Acid; D012694:Serine; D017346:Protein Serine-Threonine Kinases