Activation of PI 3-kinase by G protein betagamma subunits.
We have reported that fMLP-induced activation of pertussis toxin-sensitive GTP-binding proteins in THP-1 cells potentiates the insulin-induced accumulation of PtdIns(3,4,5)P3, a product of phosphoinositide 3-kinase (T. Okada et al., Biochem. J. 317, 475-480, 1996). The synergism in PtdIns(3,4,5)P3 accumulation was observed in Chinese hamster ovary cells expressing both insulin and fMLP receptors. In rat adipocytes, which represent the physiological target cells of insulin, receptor-mediated activation of GTP-binding protein by adenosine and prostaglandin E2 potentiated the insulin-induced PtdIns(3,4,5)P3 accumulation. In cell-free systems, the activity of the p85/p110beta subtype of phosphoinositide 3-kinase was, while that of p85/p110alpha was not, stimulated by the betagamma subunits of the GTP-binding proteins. We propose here a hypothesis that the p85/p110beta subtype is under the control of both the insulin receptors and the GTP-binding protein-coupled receptors in intact cell systems.
Hazeki
O
O
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan. hazeki@mol.f.u-tokyo.ac.jp
Okada
T
T
Kurosu
H
H
Takasuga
S
S
Suzuki
T
T
Katada
T
T
D000818:Animals; D016466:CHO Cells / Q000378:metabolism; D006224:Cricetinae; D019281:Dimerization; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D046911:Macromolecular Substances; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D051381:Rats; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism; D012680:Sensitivity and Specificity; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007328:Insulin; D046911:Macromolecular Substances; D018129:Phosphatidylinositol Phosphates; D010761:Phosphorus Radioisotopes; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D010566:Virulence Factors, Bordetella; C060974:phosphatidylinositol 3,4,5-triphosphate; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases; D019204:GTP-Binding Proteins