Thrombopoietin, c‐Mpl ligand, induces tyrosine phosphorylation of Tyk2, JAK2, and STAT3, and enhances agonists‐induced aggregation in platelets in vitro

Abstract

We investigated in vitro effects of recombinant human thrombopoietin (TPO), or c‐Mpl ligand, on human platelets. TPO induced rapid dose‐dependent tyrosine phosphorylation of several proteins. We identified Janus tyrosine kinases, Tyk2 and JAK2, and a member of STAT (signal transducers and activators of transcription) family, STAT3, as the tyrosine‐phosphorylated proteins in response to TPO. TPO by itself did not cause platelet aggregation and shape change, but augmented ADP‐induced aggregation in a dose‐dependent manner. Acetylsalicylic acid inhibited the secondary aggregation enhanced by TPO, but not the TPO‐induced potentiation of the primary aggregation. TPO modulates platelet activation possibly through protein‐tyrosine phosphorylation.