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 language | English (US) |
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Pages (from-to) | 11221-11229 |
Number of pages | 9 |
Journal | Journal of Biological Chemistry |
Volume | 282 |
Issue number | 15 |
DOIs | |
State | Published - Apr 13 2007 |
Externally published | Yes |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology