[Platelet activation mediated through membrane glycoproteins: involvement of tyrosine kinases]

Platelet membrane glycoproteins such as GPIb and GPIa/IIa play important roles in platelet functional responses. They are the receptors for specific ligands (GPIb for von Willebrand factors, and GPIa/IIa for collagen), and the ligand-receptor interaction is the first step that elicits downstream intracellular activation signals which finally culminate in platelet aggregation. Although a variety of signal transduction pathways may be involved, tyrosine kinases appear to be most closely related to platelet activation mediated by membrane glycoproteins. Since its discovery in early 1980's, protein tyrosine phosphorylation catalyzed by tyrosine kinases has been recognized to play a role in regulating the cell function of various cells. Platelets have several Src family tyrosine kinases with an SH2 domain and an SH3 domain. Syk with two SH2 domains also appears to play an important role in platelet activation, especially in its early phase. The SH2 domain binds to a phosphorylated tyrosine residue of other proteins, and the SH3 domain recognizes proline-rich domains of target proteins, thus providing the anchoring sites for protein-protein interactions. In this article, some of the recent developments in the signal transduction pathways related with tyrosine kinases are introduced. Several signaling molecules involved in GPIb- or GPIa/IIa-mediated platelet activation have been identified. Interestingly, the members participating in these processes are distinct, suggesting a diversity of signal transduction mechanisms.