Phosphorylation of beta-catenin by AKT promotes beta-catenin transcriptional activity.
Increased transcriptional activity of beta-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 beta-catenin at Ser552 in vitro and in vivo. AKT-mediated phosphorylation of beta-catenin causes its disassociation from cell-cell contacts and accumulation in both the cytosol and the nucleus and enhances its interaction with 14-3-3zeta via a binding motif containing Ser552. Phosphorylation of beta-catenin by AKT increases its transcriptional activity and promotes tumor cell invasion, indicating that AKT-dependent regulation of beta-catenin plays a critical role in tumor invasion and development.
Fang
Dexing
D
Brain Tumor Center and Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Hawke
David
D
Zheng
Yanhua
Y
Xia
Yan
Y
Meisenhelder
Jill
J
Nika
Heinz
H
Mills
Gordon B
GB
Kobayashi
Ryuji
R
Hunter
Tony
T
Lu
Zhimin
Z
D048948:14-3-3 Proteins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015534:Trans-Activators; D014158:Transcription, Genetic / Q000235:genetics*; D051176:beta Catenin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
D048948:14-3-3 Proteins; D015534:Trans-Activators; D051176:beta Catenin; D010768:Phosphoserine; D051057:Proto-Oncogene Proteins c-akt