Protein phosphatase 1 regulates assembly and function of the β-catenin degradation complex

Wen Luo, Annita Peterson, Benjamin A. Garcia, Gary Coombs, Bente Kofahl, Reinhart Heinrich, Jeffrey Shabanowitz, Donald F. Hunt, H. Joseph Yost, David M. Virshup

Research output: Contribution to journalArticlepeer-review

97 Scopus citations


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.

Original languageEnglish
Pages (from-to)1511-1521
Number of pages11
JournalEMBO Journal
Issue number6
StatePublished - Mar 21 2007


  • Axin
  • CKI
  • GSK3
  • PP1
  • Wnt/β-catenin


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