Abstract
Human platelets contain a large quantity of Ca2+-activated, phospholipiddependent protein kinase originally found in rat brain (Takai, Y., Kishimoto, A., Iwasa, Y., Kawahara, Y., Mori, T. and Nishizuka, Y. (1979) J. Biol. Chem. 254, 3692-3695). The activation of this enzyme appears to be directly coupled to phosphatidylinositol (PI) turnover which is induced by thrombin, since at micromolar concentrations of Ca2+ the enzyme absolutely depends on phospholipid as well as on a small amount of unsaturated diacylglycerol which is derived from the PI turnover. Among various phospholipids phosphatidylserine is the most active. The enzyme thus activated phosphorylates preferentially an endogenous protein having a molecular weight of 40, 000 in vitro. This protein is also shown to be phosphorylated rapidly in platelets in vivo which are stimulated by thrombin. The phosphorylation of this protein is generally accepted to be intimately related to the thrombin-induced serotonin release. Such phosphorylation in vitro as well as in vivo is profoundly and selectively inhibited in parallel manners by phospholipid-interacting drugs such as dibucaine and chlorpromazine, both of which are known to inhibit platelet activation. These results suggest that PI turnover plays a role in transmembrane control of protein phosphorylation during the thrombin-induced activation of human platelets.
