title: Thrombopoietin modulates platelet activation in vitro through protein-tyrosine phosphorylation.
abstract: 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.
authors.affiliation: Department of Clinical Laboratory Medicine, Kagawa Medical School, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kubota
authors.forename: T
authors.initials: T
authors.lastname: Arai
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: G
authors.initials: G
authors.lastname: Yamaoka
authors.forename: H
authors.initials: H
authors.lastname: Kiuchi
authors.forename: T
authors.initials: T
authors.lastname: Kajikawa
authors.forename: K
authors.initials: K
authors.lastname: Kawanishi
authors.forename: H
authors.initials: H
authors.lastname: Ohnishi
authors.forename: M
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: J
authors.initials: J
authors.lastname: Takahara
authors.forename: S
authors.initials: S
authors.lastname: Irino
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology*; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects*; D011506:Proteins / Q000378:metabolism; D013926:Thrombopoietin / Q000494:pharmacology*; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D011506:Proteins; D014443:Tyrosine; D000244:Adenosine Diphosphate; D013926:Thrombopoietin