INTEGRIN-DEPENDENT PROTEIN DEPHOSPHORYLATION ON TYROSINE INDUCED BY ACTIVATION OF THE THROMBIN RECEPTOR IN HUMAN PLATELETS

Activation of human platelets by thrombin or a thrombin receptor-activ ating peptide (TRAP) resulted in a decrease in tyrosine phosphorylatio n of two proteins, P38 and P140. Preincubation of platelets with the t yrosine phosphatase inhibitor orthovanadate prevented the tyrosine dep hosphorylation of P38 and P140, and reduced platelet aggregation induc ed by thrombin receptor activation. When platelets were stimulated und er conditions that precluded the activation of glycoprotein IIb/IIIa ( dissociation of the complex by EGTA at 37 degrees C) or the binding of fibrinogen (preincubation of platelets with RGDS), tyrosine dephospho rylation of P38 and P140 was not observed. The results indicate that p rotein tyrosine phosphatase stimulation (a) occurs during platelet act ivation induced by a physiological stimulus, (b) is a positive regulat ory signal for platelet aggregation and (c) is dependent on the activa tion of the integrin alpha(IIb)beta(3).