Kubota Y, Arai T, Tanaka T, Yamaoka G, Kiuchi H, Kajikawa T, Kawanishi K, Ohnishi H, Yamaguchi M, Takahara J, Irino S
Department of Clinical Laboratory Medicine, Kagawa Medical School, Japan.
Stem Cells. 1996 Jul;14(4):439-44. doi: 10.1002/stem.140439.
To determine the roles of thrombopoietin (TPO) in platelet function in vitro, we examined the effects of TPO on platelet aggregation. Although several proteins in platelets were tyrosine-phosphorylated by TPO treatment, TPO alone was unable to induce platelet aggregation. However, the secondary wave of platelet aggregation induced by adenosine diphosphate (ADP) was enhanced by TPO in a dose-dependent manner. TPO in conjunction with ADP augmented tyrosine phosphorylation of platelet proteins, including tyrosine-phosphorylated proteins induced by TPO alone. Genistein inhibited protein-tyrosine phosphorylation in platelets induced by TPO with ADP and suppressed TPO-enhanced platelet aggregation. Moreover, tyrosine phosphorylation of MAP-kinases induced by TPO alone and TPO with ADP was consistent with TPO-enhanced platelet aggregation. These findings in the present study suggest that signal transduction involved in TPO-enhanced platelet aggregation is mediated in part by tyrosine-phosphorylated proteins, including MAP-kinases, in platelets through TPO-stimulated c-Mpl, TPO receptor.
为了确定血小板生成素（TPO）在体外血小板功能中的作用，我们研究了TPO对血小板聚集的影响。尽管通过TPO处理可使血小板中的几种蛋白质发生酪氨酸磷酸化，但单独使用TPO无法诱导血小板聚集。然而，TPO以剂量依赖的方式增强了由二磷酸腺苷（ADP）诱导的血小板聚集的第二波。TPO与ADP联合可增强血小板蛋白的酪氨酸磷酸化，包括单独由TPO诱导的酪氨酸磷酸化蛋白。染料木黄酮抑制了由TPO与ADP诱导的血小板中的蛋白酪氨酸磷酸化，并抑制了TPO增强的血小板聚集。此外，单独由TPO以及TPO与ADP诱导的丝裂原活化蛋白激酶（MAP激酶）的酪氨酸磷酸化与TPO增强的血小板聚集一致。本研究中的这些发现表明，TPO增强的血小板聚集中涉及的信号转导部分是通过血小板中酪氨酸磷酸化的蛋白质介导的，包括通过TPO刺激的c-Mpl（TPO受体）介导的MAP激酶。
