A G-protein beta gamma-subunit-responsive phosphoinositide 3-kinase activity in human platelet cytosol

J Biol Chem. 1994 Jun 17;269(24):16525-8.

Abstract

Thrombin activates phosphoinositide 3-kinase (PI 3-kinase) in platelets via a mechanism involving G-proteins, possibly of both the heterotrimeric and the low molecular weight families. We have investigated the regulation of PI 3-kinase present in platelet cytosol, and we show that this activity can be stimulated by a mixed preparation of G-protein beta gamma-subunits. This stimulation is reversed by preincubation of the beta gamma-subunits with GDP-liganded alpha-subunits. The beta gamma-stimulated activity is inhibited by wortmannin, a recently identified inhibitor of PI 3-kinase in other systems. In addition, the activity associates with PDGF receptor phosphotyrosyl peptide and monoclonal antibody designed to interact with the p85 subunit of PI 3-kinase. We suggest that this beta gamma-sensitive activity is related to previously identified forms of PI 3-kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstadienes / pharmacology
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Blood Platelets / enzymology*
  • Brain / metabolism
  • Cattle
  • Cell Membrane / metabolism
  • Cytosol / enzymology
  • GTP-Binding Proteins / isolation & purification
  • GTP-Binding Proteins / metabolism*
  • Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
  • Humans
  • Kinetics
  • Macromolecular Substances
  • Peptide Fragments / pharmacology
  • Phosphatidylinositol 3-Kinases
  • Phosphopeptides / pharmacology
  • Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors
  • Phosphotransferases (Alcohol Group Acceptor) / blood*
  • Receptors, Platelet-Derived Growth Factor / metabolism
  • Wortmannin

Substances

  • Androstadienes
  • Antibodies, Monoclonal
  • Macromolecular Substances
  • Peptide Fragments
  • Phosphopeptides
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor)
  • Receptors, Platelet-Derived Growth Factor
  • GTP-Binding Proteins
  • Wortmannin