Anti-CD9 monoclonal antibody elicits staurosporine inhibitable phosphatidylinositol 4,5-bisphosphate hydrolysis, phosphatidylinositol 3,4-bisphosphate synthesis, and protein-tyrosine phosphorylation in human platelets.
Phosphoinositide metabolism elicited by anti-CD9 monoclonal antibody, a well-characterized platelet activator, was studied using acetylsalicylic acid-treated human platelets. TP82, which is an anti-CD9 monoclonal antibody, induced classical phosphatidylinositol 4,5-bisphosphate hydrolysis, as monitored by intracellular Ca2+ mobilization and phosphatidic acid production, and synthesis of phosphatidylinositol 3,4-bisphosphate, which is a major component of newly-described 3-phosphorylated inositol phospholipids produced during platelet activation. These changes were severely inhibited by 1 microM staurosporine, a potent, though non-selective, protein kinase inhibitor, which also abolished TP82 induction of tyrosine phosphorylation of multiple platelet proteins. Protein-tyrosine phosphorylation appears necessary to initiate both the classical phosphoinositide turnover and synthesis of the newly-described 3-phosphorylated inositol phospholipids in anti-CD9 monoclonal antibody-induced platelet activation.
Department of Laboratory Medicine, Yamanashi Medical College, Japan.
Y
Y
Yatomi
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Y
Ozaki
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Satoh
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Kume
D000470:Alkaloids / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology*; D001792:Blood Platelets / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000096:biosynthesis* / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D019311:Staurosporine; D060245:Tetraspanin 29; D014443:Tyrosine / Q000378:metabolism
D000470:Alkaloids; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C554869:CD9 protein, human; D008562:Membrane Glycoproteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D060245:Tetraspanin 29; C060980:phosphatidylinositol 3,4-diphosphate; D014443:Tyrosine; D011493:Protein Kinase C; D019311:Staurosporine