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Radiolabeling and Quantification of Cellular Levels of Phosphoinositides by High Performance Liquid Chromatography-coupled Flow Scintillation
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Phosphoinositide 3-kinase in disease: timing, location, and scaffolding

Matthias P Wymann1, Romina Marone

  • 1Inst. Biochemistry and Genetics, Dept. Clinical and Biological Sciences, Centre of Biomedicine, University of Basel, Mattenstrasse 28, CH-4058, Basel. Matthias.Wymann@UniBas.CH

Current Opinion in Cell Biology
|March 23, 2005
PubMed

Insights

Dereguled phosphoinositide 3-kinases (PI3Ks) cause disease by increasing cell growth and motility. PI3Kgamma

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • Phosphoinositide 3-kinases (PI3Ks) pathway deregulation, marked by phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3) accumulation, drives increased cell growth, proliferation, and survival.
  • The PI3K/PKB/TOR signaling axis is crucial for regulating protein synthesis and cell growth.
  • PtdIns(3,4,5)P3 also activates Rho GTPases, influencing cell motility, and PI3K activity is implicated in various diseases including cancer, inflammation, and cardiovascular conditions.

Purpose of the Study:

  • To investigate the specific roles of PI3K isoforms in disease pathogenesis.
  • To elucidate the precise function of PI3Kgamma in cellular processes, particularly in the cardiac system.

Main Methods:

  • Analysis of PI3K signaling pathways and PtdIns(3,4,5)P3 accumulation.
  • Investigation of the PI3K/PKB/TOR axis in cell growth and proliferation.
  • Examination of Rho GTPase activation and its role in cell motility.
  • Specific studies on PI3Kgamma's function in the cardiac system, assessing its lipid kinase activity and scaffolding role.

Main Results:

  • Aberrant PI3K activity leads to PtdIns(3,4,5)P3 accumulation, promoting cell growth, proliferation, and survival.
  • The PI3K/PKB/TOR pathway is confirmed to control protein synthesis and growth.
  • PtdIns(3,4,5)P3-mediated activation of Rho GTPases is shown to direct cell motility.
  • Recent findings indicate PI3Kgamma acts as a scaffold protein in the cardiac system, regulating cAMP levels, but does not function as a lipid kinase in this context.

Conclusions:

  • While increased PtdIns(3,4,5)P3 is a known disease driver, identifying the implicated PI3K isoform remains challenging.
  • PI3Kgamma's role in the cardiac system is primarily structural (scaffolding) rather than enzymatic (lipid kinase), impacting cAMP regulation.

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