Phosphorylation of β-catenin by AKT promotes β-catenin transcriptional activity

Dexing Fang, David Hawke, Yanhua Zheng, Yan Xia, Jill Meisenhelder, Heinz Nika, Gordon B. Mills, Ryuji Kobayashi, Tony Hunter, Zhimin Lu

    Research output: Contribution to journalArticle

    554 Scopus citations

    Abstract

    Increased transcriptional activity of β-catenin resulting from Wnt/Wingless-dependent or -independent signaling has been detected in many types of human cancer, but the underlying mechanism of Wnt-independent regulation is poorly understood. We have demonstrated that AKT, which is activated downstream from epidermal growth factor receptor signaling, phosphorylates β-catenin at Ser552 in vitro and in vivo. AKT-mediated phosphorylation of β-catenin causes its disassociation from cell-cell contacts and accumulation in both the cytosol and the nucleus and enhances its interaction with 14-3-3ζ via a binding motif containing Ser552. Phosphorylation of β-catenin by AKT increases its transcriptional activity and promotes tumor cell invasion, indicating that AKT-dependent regulation of β-catenin plays a critical role in tumor invasion and development.

    Original languageEnglish (US)
    Pages (from-to)11221-11229
    Number of pages9
    JournalJournal of Biological Chemistry
    Volume282
    Issue number15
    DOIs
    StatePublished - Apr 13 2007

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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