ERBSTATIN BLOCKS PLATELET ACTIVATING FACTOR-INDUCED PROTEIN-TYROSINE PHOSPHORYLATION, POLYPHOSPHOINOSITIDE HYDROLYSIS, PROTEIN KINASE-C ACTIVATION, SEROTONIN SECRETION AND AGGREGATION OF RABBIT PLATELETS

The role of protein-tyrosine phosphorylation in the signal transduction of platelet activating factor (PAF) was investigated in rabbit platelets with a range of synthetic compounds that inhibit protein-tyrosine kinases. In particular, erbstatin (IC50~20 μg ml) abrogated a wide range of platelet responses to PAF, including tyrosine phosphorylation of cellular proteins, polyphosphoinositide turnover, activation of membranous protein kinase C, platelet aggregation, and serotonin secretion. With about a third of the potency of erbstatin, compound RG50864 also inhibited many of these responses, whereas at 100 μg ml, genistein, 670C88 and ST271 were without effect. Finally, the ability of thrombin to cause platelet aggregation and serotonin secretion was also compromised by erbstatin. © 1990.