TAILIEUCHUNG - Báo cáo khoa học: Glycoprotein Ib-mediated platelet activation A signalling pathway triggered by thrombin

Platelet activation by thrombin plays a major role in the development of haemostasis and thrombosis. Thrombin activates human platelets by cleaving the N-terminal region of G-protein-coupled protease-activated receptors (PARs). On the other hand, the platelet membrane glycoprotein GPIb acts as a thrombin-binding site and promotes platelet activation by low thrombin present here new evidence in favour of a thrombin receptor function for GPIb. We have selected conditions in which thrombin– GPIb interactions were enhanced by thrombin immobiliza-tion | Eur. J. Biochem. 270 2959-2970 2003 FEBS 2003 doi Glycoprotein Ib-mediated platelet activation A signalling pathway triggered by thrombin Frederic Adam1 Marie-Claude Guillin1 2 and Martine Jandrot-Perrus1 1INSERM E0348 Faculte Xavier Bichat Paris 2Hématologie et Immunologie Hopital Bichat AP-HP Paris France Platelet activation by thrombin plays a major role in the development of haemostasis and thrombosis. Thrombin activates human platelets by cleaving the N-terminal region of G-protein-coupled protease-activated receptors PARs . On the other hand the platelet membrane glycoprotein GPIb acts as a thrombin-binding site and promotes platelet activation by low thrombin concentrations. We present here new evidence in favour of a thrombin receptor function for GPIb. We have selected conditions in which thrombin-GPIb interactions were enhanced by thrombin immobilization. Activation was studied independently of PAR ce Lv ag e by using active-site-blocked thrombin. We show that immobilized proteolytically inactive thrombin induces platelet adhesion and spreading dense granule secretion and integrin oIIbp3-dependent platelet-platelet interactions. The pathway must be dependent on GPIb because it is deficient in platelets from a patient with Bernard Soulier syndrome and inhibited by a monoclonal antibody to GPIb SZ2 or by an excess of glycocalicin. Secreted ADP plays a major role in GPIb-dependent thrombin-induced platelet activation which is in addition regulated by cAMP concentration. Thrombin-induced GPIb-dependent platelet activation leads to tyrosyl phosphorylation of several proteins. Inhibition of platelet-platelet interactions and protein tyrosine phosphorylations by inhibitors of phosphatidylinositol 3-kinases and protein kinase C implies that activation of the latter are important steps of the GPIb-coupled signalling pathway triggered by thrombin. Keywords glycoprotein Ib platelets signalling thrombin. Platelet activation by .

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