Elsevier

Developmental Biology

Volume 223, Issue 2, 15 July 2000, Pages 441-448
Developmental Biology

Regular Article
A Mode of Regulation of β-Catenin Signaling Activity in Xenopus Embryos Independent of Its Levels

https://doi.org/10.1006/dbio.2000.9770Get rights and content
Under an Elsevier user license
open archive

Abstract

The signaling activity of β-catenin is thought to be regulated by phosphorylation of a cluster of N-terminal serines, putative sites for GSK3β. In the prevailing model in the literature, GSK3β-dependent phosphorylation of these sites targets β-catenin for ubiquitin-mediated degradation. Wnt signaling inhibits GSK3β activity and this blocks degradation, allowing β-catenin to accumulate and signal. We show here that β-catenin activity is not regulated solely by protein stability. Mutations in the putative GSK3β phosphorylation sites of β-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 β-catenin signaling in addition to the effects these sites exert upon protein stability.

Keywords

signal transduction
GSK3β
Wnts
Xenopus.

Cited by (0)

1

To whom correspondence should be addressed at the Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, Box 564, 1275 York Avenue, New York, NY 10021. Fax: (212) 717-3047. E-mail: [email protected].