Phosphatidylinositol 3 '-kinase and tyrosine-phosphatase activation positively modulate Convulxin-induced platelet activation. Comparison with collagen

In this report we have studied the role of phosphatidylinositol 3'-kinase ( PI3-K) and tyrosine phosphatase activation on platelet activation by Convul xin (Cvx), Wortmannin, a specific PI3-K inhibitor, and phenylarsine oxide ( PAO), a sulfhydryl reagent that inhibits tyrosine phosphatase (PTPase), blo ck Cvx-induced platelet aggregation, granule secretion, inositol phosphate production, and increase in [Ca2+](i). However, PAO does not inhibit Cvx-in duced tyrosine phosphorylation of platelet proteins, including Syk and PLC gamma 2, but blocked collagen-induced platelet aggregation as well as tyros ine phosphorylation of PLC gamma 2. In contrast, Cvx-induced PLC gamma 2 ty rosyl phosphorylation was partially inhibited by wortmannin, We conclude th at (i) although Cvx and collagen activate platelets by a similar mechanism, different regulatory processes are specific to each agonist; (ii) mechanis ms other than tyrosine phosphorylation regulate PLC gamma 2, activity; and (iii) besides protein tyrosine kinases, PI3-K land PTPase) positively modul ate platelet activation by both Cvx and collagen, and this enzyme is requir ed for effective transmission of GPVI-Fc receptor gamma chain signal to res ult in full activation and tyrosine phosphorylation of PLC gamma 2 in Cvx-s timulated platelets. (C) 1999 Federation of European Biochemical Societies.