Analysis of signal transduction pathways through glycoprotein Ib in human platelets.

点击翻译按钮获取中文摘要

In vivo platelet adhesion to the damaged vessel wall and subsequent platelet-platelet interaction is essential for hemostasis and thrombogenesis. The most initial step involved in this process is the interaction between the glycoprotein Ib (GPIb) and von Willebrand factor (vWF).A number of snake venoms (botrocetin, alboaggregin-B, echicetin, Jararaca GPIb-BP, flavocetin-A) have been identified that affect the interaction between vWF and GPIb. They have proved to be valuable tools for elucidating the biological mechanism underling the GPIb-related platelet activation. In this study, we compared the effects of these GPIb-binding proteins on various parameters of platelet activation. Association of GPIb and Src, tyrosine phosphorylation of 64kDa protein, and platelet aggregation were induced by alboaggregin-B and flavocetin-A.In addition to those reactions, redistribution of Src, Lyn, and 14-3-3 to cytoskeletons and Ca^<++> influx were induced by botrocetin in the presence of vWF.However, botrocetin, in the presence of monomeric vWF, could not induced platelet aggregation, Ca^<2+> influx, and cytoskeletal association of tyrosine kinases. Echicetin or Jararaca GPIb-BP caused no reaction in these parameters.These results suggested that tyrosine kinase might be strongly related in GPIb signal transduction(s). Since botrocetin could not induce platelet activation in the presence of monomeric vWF, the activation of platelets appear to require the clustering of GPIb by the vWF molecules with multiple binding sites.