The p85beta regulatory subunit of PI3K serves as a substrate for PTEN protein phosphatase activity during insulin mediated signaling

Biochem Biophys Res Commun. 2010 Jul 2;397(3):513-9. doi: 10.1016/j.bbrc.2010.05.146. Epub 2010 May 31.


Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor gene that is frequently mutated in brain, uterine, and prostate cancers. The protein phosphatase activity is poorly defined. We demonstrate that insulin stimulates phosphorylation of tyrosine and threonine/proline residues on the p85 regulatory subunit of PI3K in Huh-7, and HEK 293 cells. The specificity of PTEN binding and dephosphorylation of PI3K appears to reside on the p85beta subunit. Therefore, the PTEN phosphatase is active against the PI3K p85beta subunit and dephosphorylates a protein involved in insulin signaling where known downstream consequences are increased cell migration, motility, and invasion.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Catalytic Domain / genetics
  • Cell Line
  • Humans
  • Insulin / metabolism*
  • Insulin / pharmacology
  • Mutation
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphorylation
  • Proline / metabolism
  • Protein Subunits / metabolism
  • Proto-Oncogene Proteins c-akt / agonists
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Threonine / metabolism
  • Tyrosine / metabolism


  • Insulin
  • Protein Subunits
  • Threonine
  • Tyrosine
  • Proline
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase