Uncovering the PI3Ksome: phosphoinositide 3-kinases and counteracting PTEN form a signaling complex with intrinsic regulatory properties

Mol Cell Biol. 2014 Sep 15;34(18):3356-8. doi: 10.1128/MCB.00920-14. Epub 2014 Jul 21.

Abstract

Production of the phosphoinositide lipid phosphatidylinositol (3,4,5)trisphosphate [PI(3,4,5)P3, or PIP3] by class I phosphoinositide 3-kinases (PI3Ks) is a major signaling mechanism whose deregulation contributes to serious diseases, including cancer. New findings suggest that tyrosine kinase receptor engagement results in the assembly of hetero-oligomeric PI3K complexes in which PI3Kα first activates PI3Kβ, and PI3K catalytic activity then promotes recruitment and activation of the PIP3-removing tumor suppressor PTEN. Thus, PIP3 production is fine-tuned through formation of an intrinsically regulated "PI3Ksome."

Publication types

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

MeSH terms

  • Catalytic Domain
  • Class I Phosphatidylinositol 3-Kinases / metabolism*
  • Gene Expression Regulation
  • Humans
  • PTEN Phosphohydrolase / metabolism*
  • Phosphatidylinositol Phosphates / metabolism*
  • Signal Transduction

Substances

  • Phosphatidylinositol Phosphates
  • Class I Phosphatidylinositol 3-Kinases
  • PTEN Phosphohydrolase