Ionophore A23187-induced protein-tyrosine phosphorylation of human platelets: possible synergism between Ca2+ mobilization and protein kinase C activation. |
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Authors: | H Takayama T Nakamura S Yanagi T Taniguchi S Nakamura H Yamamura |
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Institution: | First Department of Internal Medicine, Fukui Medical School, Japan. |
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Abstract: | Addition of ionophore A23187 to washed human platelets caused a time- and dose-dependent increase in the phosphotyrosyl content of 135, 124 and 76 kDa proteins. Platelets loaded with intracellular Ca2+ chelator 5,5'-dimethyl-bis-(o-aminophenoxy)-ethane-N, N, N', N'-tetraacetic acid before addition of A23187 exhibited no protein-tyrosine phosphorylation. Replenishment of such platelets with extracellular CaCl2 restored A23187-induced protein-tyrosine phosphorylation. Upon stimulation with A23187, both aspirin and ADP scavengers-treated platelets exhibited protein-tyrosine phosphorylation without phosphoinositide hydrolysis and protein kinase C activation. These data show (a) that A23187 stimulates protein-tyrosine phosphorylation by the elevation of intracellular Ca2+, and (b) that A23187-induced protein-tyrosine phosphorylation is independent of formation of endoperoxides/thromboxane A2, released ADP, phosphoinositide hydrolysis and protein kinase C activation. Furthermore, a synergistic effect of A23187 and protein kinase C activators in stimulating protein-tyrosine phosphorylation is suggested. |
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