Calpains are involved in phosphatidylinositol 3′,4′-bisphosphate synthesis dependent on the αIIbβ3 integrin engagement in thrombin-stimulated platelets

Abstract In thrombin-stimulated platelets α IIb β 3 integrin engagement triggers both phosphatidylinositol 3′,4′- bis phosphate synthesis and calpain activation. We checked the possible involvement of calpains in phosphatidylinositol 3-kinase signalling pathway using a cell permeant specific inhibitor of calpains, calpeptin. In conditions where thrombin-induced platelet aggregation and secretion were not impaired, we found a dose-dependent inhibition of phosphatidylinositol 3,4- bis phosphate synthesis by calpeptin from 50 μg/ml. Moreover, pretreatment of platelets by both calpeptin and the peptide RGDS, an inhibitor of fibrinogen binding to activated α IIb β 3 integrin, did not induce additive effects on phosphatidylinositol 3,4- bis phosphate inhibition. Finally, the p85 regulatory subunit of phosphatidylinositol 3-kinase was still translocated to the cytoskeleton in calpeptin-treated platelets. These data indicate that calpains are involved in the regulation of α IIb β 3 integrin-dependent phosphatidylinositol 3-kinase signalling pathway. © 1997 Federation of European Biochemical Societies.