Protein Tyrosine Phosphorylation in Platelets

Abstract

This chapter discusses the protein tyrosine phosphorylation in platelets. Activation of platelets by diverse platelet agonists causes platelet aggregation and secretion and is associated with a rapid induction of tyrosine phosphorylation of multiple proteins. The phosphorylation of these proteins occurs in several temporal phases and is mediated by distinct receptor-activated signal transduction pathways. “Early” phosphorylation events occur within seconds after agonist stimulation and are independent of fibrinogen binding to its integrin receptor, α IIb β3. Fibrinogen binding to α IIb β3 stimulates another wave of tyrosine phosphorylation. Finally, platelet aggregation mediated by fibrinogen cross-linking of stirred platelets induces tyrosine phosphorylation of still another set of proteins. Multiple tyrosine protein kinases appear to be involved in the phosphorylation of these proteins, and cytoskeletal interactions with appear to play an important role in coupling protein tyrosine kinases with α IIb β3. This evidence, together with the ability of protein tyrosine kinase inhibitors to block critical steps in agonist-induced aggregation and secretion, has implicated protein tyrosine phosphorylation as a possible regulatory mechanism during platelet activation. Studies have clearly demonstrated both a role for integrin receptors in the regulation of tyrosine phosphorylation and the utility of platelets in examining intracellular signal transduction events that are regulated by integrin family receptors. The challenge that now faces investigators in this area is to identify the substrates that are phosphorylated on tyrosine and to establish the role of these substrates in platelet signal transduction.