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
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Research Support, Non-U.S. Gov't
MeSH terms
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Androstadienes / pharmacology
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Animals
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Antibodies, Monoclonal / pharmacology
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Blood Platelets / enzymology*
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Brain / metabolism
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Cattle
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Cell Membrane / metabolism
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Cytosol / enzymology
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GTP-Binding Proteins / isolation & purification
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GTP-Binding Proteins / metabolism*
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Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
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Humans
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Kinetics
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Macromolecular Substances
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Peptide Fragments / pharmacology
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Phosphatidylinositol 3-Kinases
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Phosphopeptides / pharmacology
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Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors
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Phosphotransferases (Alcohol Group Acceptor) / blood*
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Receptors, Platelet-Derived Growth Factor / metabolism
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Wortmannin
Substances
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Androstadienes
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Antibodies, Monoclonal
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Macromolecular Substances
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Peptide Fragments
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Phosphopeptides
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Guanosine 5'-O-(3-Thiotriphosphate)
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Phosphatidylinositol 3-Kinases
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Phosphotransferases (Alcohol Group Acceptor)
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Receptors, Platelet-Derived Growth Factor
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GTP-Binding Proteins
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Wortmannin