THROMBOPOIETIN, C-MPL LIGAND, INDUCES TYROSINE PHOSPHORYLATION OF TYK2, JAK2, AND STAT3, AND ENHANCES AGONISTS-INDUCED AGGREGATION IN PLATELETS IN-VITRO

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.