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Title: Membrane-associated 41-kDa GTP-binding protein in collagen-induced platelet activation

Initially we established that the binding of collagen to human blood platelets stimulates both the rapid loss of PIP2 and the generation of inositol-4,5-bisphosphate (IP2) and inositol-1,4,5-triphosphate (IP3). These results indicate that the binding of collagen stimulates inositol phospholipid-specific phospholipase C during platelet activation. The fact that GTP or GTP-gamma-S augments, and pertussis toxin inhibits, collagen-induced IP3 formation suggests that a GTP-binding protein or (or proteins) may be directly involved in the regulation of phospholipase C-mediated phosphoinositide turnover in human platelets. We have used several complementary techniques to isolate and characterize a platelet 41-kDa polypeptide (or polypeptides) that has a number of structural and functional similarities to the regulatory alpha i subunit of the GTP-binding proteins isolated from bovine brain. This 41-kDa polypeptide (or polypeptides) is found to be closely associated with at least four membrane glycoproteins (e.g., gp180, gp110, gp95, and gp75) in a 330-kDa complex that can be dissociated by treatment with high salt plus urea. Most important, we have demonstrated that antilymphoma 41-kDa (alpha i subunit of GTP-binding proteins) antibody cross-reacts with the platelet 41-kDa protein (or proteins) and the alpha i subunit of bovine brain Gi alpha proteins, and blocks GTP/collagen-induced IP3 formation. These data providemore » strong evidence that the 41-kDa platelet GTP-binding protein (or proteins) is directly involved in collagen-induced signal transduction during platelet activation.« less
Authors:
;  [1]
  1. (Univ. of Miami Medical School, FL (USA))
Publication Date:
OSTI Identifier:
6623020
Resource Type:
Journal Article
Resource Relation:
Journal Name: FASEB Journal (Federation of American Societies for Experimental Biology); (USA); Journal Volume: 4:11
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; COLLAGEN; BIOCHEMICAL REACTION KINETICS; LIPASES; ENZYME ACTIVITY; MEMBRANE PROTEINS; BIOLOGICAL FUNCTIONS; PHOSPHOLIPIDS; BIOSYNTHESIS; ADP; AUTORADIOGRAPHY; BLOOD PLATELETS; INHIBITION; MOLECULAR WEIGHT; PHOSPHORUS ISOTOPES; TOXINS; ANTIGENS; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BODY FLUIDS; CARBOXYLESTERASES; ENZYMES; ESTERASES; ESTERS; FUNCTIONS; HYDROLASES; ISOTOPES; KINETICS; LIPIDS; MATERIALS; NUCLEOTIDES; ORGANIC COMPOUNDS; ORGANIC PHOSPHORUS COMPOUNDS; PROTEINS; REACTION KINETICS; SCLEROPROTEINS; SYNTHESIS; TOXIC MATERIALS 550201* -- Biochemistry-- Tracer Techniques