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. 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.
Kubota
Y
Y
Department of Clinical Laboratory Medicine, Kagawa Medical School, Japan.
Arai
T
T
Tanaka
T
T
Yamaoka
G
G
Kiuchi
H
H
Kajikawa
T
T
Kawanishi
K
K
Ohnishi
H
H
Yamaguchi
M
M
Takahara
J
J
Irino
S
S
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*
D011506:Proteins; D014443:Tyrosine; D000244:Adenosine Diphosphate; D013926:Thrombopoietin