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

J Biol Chem. 2007 Apr 13;282(15):11221-9. doi: 10.1074/jbc.M611871200. Epub 2007 Feb 7.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / metabolism
  • Amino Acid Sequence
  • Animals
  • 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*
  • beta Catenin / chemistry
  • beta Catenin / genetics*
  • beta Catenin / metabolism*


  • 14-3-3 Proteins
  • Trans-Activators
  • beta Catenin
  • Phosphoserine
  • Proto-Oncogene Proteins c-akt