Presenilin couples the paired phosphorylation of β-catenin independent of axin: Implications for β-catenin activation in tumorigenesis

David E. Kang, Salvador Soriano, Xuefeng Xia, Charles G. Eberhart, Bart De Strooper, Hui Zheng, Edward H. Koo

Research output: Contribution to journalArticlepeer-review

Abstract

The Alzheimer's disease-linked gene presenilin 1 (PS1) is required for intramembrane proteolysis of APP and Notch. In addition, recent observations strongly implicate PS1 as a negative regulator of the Wnt/β-catenin signaling pathway, although the mechanism underlying this activity is unknown. Here, we show that presenilin functions as a scaffold that rapidly couples β-catenin phosphorylation through two sequential kinase activities independent of the Wnt-regulated Axin/CK1α complex. Thus, presenilin deficiency results in increased β-catenin stability in vitro and in vivo by disconnecting the stepwise phosphorylation of β-catenin, both in the presence and absence of Wnt stimulation. These findings highlight an aspect of β-catenin regulation outside of the canonical Wnt-regulated pathway and a function of presenilin separate from intramembrane proteolysis.

Original languageEnglish (US)
Pages (from-to)751-762
Number of pages12
JournalCell
Volume110
Issue number6
DOIs
StatePublished - Sep 20 2002

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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