Calpain controls the balance between protein tyrosine kinase and tyrosine phosphatase activities during platelet activation

AbstractProtein phosphorylation was studied during platelet stimulation in two ranges of ionized [Ca2+]. At ionized [Ca2+]i≤1 μM, proteins were phosphorylated. At ionized [Ca2+]i≥4 μM, phosphoproteins disappeared. Protein dephosphorylation was prevented by the combined action of calpeptin and phosphatase inhibitors. Protein tyrosine phosphatase activity was stimulated regardless of the ionized [Ca2+]i level. Protein tyrosine kinase activity was stimulated at ionized [Ca2+]i≤1 μM, whereas at ionized [Ca2+]i≥4 μM, no protein tyrosine kinase activity was observed except in the presence of calpeptin. Thus, the massive tyrosine phosphoprotein disappearance observed at a high ionized [Ca2+]i resulted not only in protein tyrosine phosphatase activation, but also in calpain-induced protein tyrosine kinase inactivation