Phosphoinositide 3-kinase in disease: timing, location, and scaffolding

Curr Opin Cell Biol. 2005 Apr;17(2):141-9. doi: 10.1016/j.ceb.2005.02.011.

Abstract

When PI3Ks are deregulated by aberrant surface receptors or modulators, accumulation of PtdIns(3,4,5)P3 leads to increased cell growth, proliferation and contact-independent survival. The PI3K/PKB/TOR axis controls protein synthesis and growth, while PtdIns(3,4,5)P3-mediated activation of Rho GTPases directs cell motility. PI3K activity has been linked to the formation of tumors, metastasis, chronic inflammation, allergy and cardiovascular disease. Although increased PtdIns(3,4,5)P3 is a well-established cause of disease, it is seldom known which PI3K isoform is implied. Recent work has demonstrated that PI3Kgamma contributes to the control of cAMP levels in the cardiac system, where the protein acts as a scaffold, but not as a lipid kinase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / metabolism*
  • Humans
  • Inflammation / metabolism
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Models, Biological
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphatidylinositol Phosphates / metabolism*
  • Protein Isoforms / metabolism
  • Receptors, Cell Surface / metabolism
  • Time Factors

Substances

  • Intracellular Signaling Peptides and Proteins
  • Phosphatidylinositol Phosphates
  • Protein Isoforms
  • Receptors, Cell Surface
  • phosphatidylinositol 3,4,5-triphosphate
  • Phosphatidylinositol 3-Kinases