Premium
Protein phosphatase 1 regulates assembly and function of the β‐catenin degradation complex
Author(s) -
Luo Wen,
Peterson Annita,
Garcia Benjamin A,
Coombs Gary,
Kofahl Bente,
Heinrich Reinhart,
Shabanowitz Jeffrey,
Hunt Donald F,
Yost H Joseph,
Virshup David M
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601607
Subject(s) - wnt signaling pathway , biology , phosphorylation , casein kinase 1 , beta catenin , gsk 3 , microbiology and biotechnology , phosphatase , protein phosphatase 1 , dephosphorylation , protein phosphatase 2 , signal transduction , catenin , lrp5 , xenopus , protein kinase a , biochemistry , gene
The Wnt/β‐catenin signaling pathway is critical in both cellular proliferation and organismal development. However, how the β‐catenin degradation complex is inhibited upon Wnt activation remains unclear. Using a directed RNAi screen we find that protein phosphatase 1 (PP1), a ubiquitous serine/threonine phosphatase, is a novel potent positive physiologic regulator of the Wnt/β‐catenin signaling pathway. PP1 expression synergistically activates, and inhibition of PP1 inhibits, Wnt/β‐catenin signaling in Drosophila and mammalian cells as well as in Xenopus embryos. The data suggest that PP1 controls Wnt signaling through interaction with, and regulated dephosphorylation of, axin. Inhibition of PP1 leads to enhanced phosphorylation of specific sites on axin by casein kinase I. Axin phosphorylation markedly enhances the binding of glycogen synthase kinase 3, leading to a more active β‐catenin destruction complex. Wnt‐regulated changes in axin phosphorylation, mediated by PP1, may therefore determine β‐catenin transcriptional activity. Specific inhibition of PP1 in this pathway may offer therapeutic approaches to disorders with increased β‐catenin signaling.