THROMBOPOIETIN MODULATES PLATELET ACTIVATION IN-VITRO THROUGH PROTEIN-TYROSINE PHOSPHORYLATION

To determine the roles of thrombopoietin (TPO) in platelet function in vitro, we examined the effects of TPO on platelet aggregation, Althou gh several proteins in platelets were tyrosine-phosphorylated by TPO t reatment, TPO alone was unable to induce platelet aggregation, However , the secondary wave of platelet aggregation induced by adenosine diph osphate (ADP) was enhanced by TPO in a dose-dependent manner, TPO in c onjunction with ADP augmented tyrosine phosphorylation of platelet pro teins, including tyrosine-phosphorylated proteins induced by TPO alone , Genistein inhibited protein-tyrosine phosphorylation in platelets in duced by TPO with ADP and suppressed TPO-enhanced platelet aggregation , Moreover, tyrosine phosphorylation of MAP-kinases induced by TPO alo ne and TPO with ADP was consistent with TPO-enhanced platelet aggregat ion, These findings in the present study suggest that signal transduct ion involved in TPO-enhanced platelet aggregation is mediated in part by tyrosine-phosphorylated proteins, including MAP-kinases, in platele ts through TPO-stimulated c-Mpl, TPO receptor.