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A POSSIBLE ROLE OF CALCIUM-ACTIVATED, PHOSPHOLIPID-DEPENDENT PROTEIN KINASE IN PLATELET ACTIVATION

English (英語)

The Kobe journal of the medical sciences

28(3)

119-132

1982-06

Human platelets contain a large quantity of Ca Z+ -activated, phospholipid-dependent protein kinase originally found in mammalian brain (Takai, Y., Kishimoto, A., Iwasa, Y., Kawahara, Y., Mori, T., and Nishizuka, Y. J. Biol. Chem. 1979. 254, 3692/3695). At the micromolar range of Ca 2+ concentrations this enzyme almost absolutely requires a small amount of unsaturated diacylglycerol, which may result from the thrombin-induced hydrolysis of phosphatidylinositol. The protein kinase thus activated is able to phosphorylate in vitro endogenous proteins, most predominantly one polypeptide having a molecular weight of approximately 40,000 (40K protein). This protein is phosphorylated rapidly in platelets stimulated by thrombin as well as by exogenous phospholipase C in vivo. This 40K protein phosphorylation in vivo appears to be preceded by diacylglycerol formation and followed by serotonin release reaction. These three reactions are inhibited to the same extent by prostaglandin El. The phosphorylation of 40K protein in vivo induced by thrombin as well as the activation of this kinase in vitro is profoundly inhibited in parallel manner by phospholipid-interacting drugs such as dibucaine and chlorpromazine, which are known to inhibit platelet activation. In human platelets cyclic nucleotide-dependent protein kinases are present in small quantities, and the enzymes are not susceptible to these drugs. The results suggest that Ca 2+ -activated, phospholipid-dependent protein kinase may be directly involved in platelet activation through the phosphorylation of 40K protein.

diacylglycerol

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