Phosphorylation of β-Catenin by AKT Promotes β-Catenin Transcriptional Activity

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 downstre...

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Bibliographic Details
Published in:The Journal of biological chemistry 2007-04, Vol.282 (15), p.11221-11229
Main Authors: Fang, Dexing, Hawke, David, Zheng, Yanhua, Xia, Yan, Meisenhelder, Jill, Nika, Heinz, Mills, Gordon B., Kobayashi, Ryuji, Hunter, Tony, Lu, Zhimin
Format: Article
Language:English
Subjects:
14-3-3 Proteins - metabolism
Amino Acid Sequence
Animals
beta Catenin - chemistry
beta Catenin - genetics
beta Catenin - metabolism
Cell Line
Cell Nucleus - metabolism
Cricetinae
Cricetulus
Cytosol - metabolism
Humans
Molecular Sequence Data
Neoplasm Invasiveness
Neoplasms - metabolism
Neoplasms - pathology
Phosphorylation
Phosphoserine - metabolism
Protein Binding
Protein Transport
Proto-Oncogene Proteins c-akt - metabolism
Trans-Activators
Transcription, Genetic - genetics
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Summary: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 Ser552in 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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M611871200