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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aspirin / pharmacology
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DNA-Binding Proteins / metabolism*
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Humans
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Janus Kinase 2
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Phosphorylation
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Platelet Aggregation / drug effects*
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Platelet Aggregation Inhibitors / pharmacology
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Protein-Tyrosine Kinases / metabolism*
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Proteins / metabolism*
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Proto-Oncogene Proteins*
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Receptors, Immunologic / metabolism*
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Recombinant Fusion Proteins / metabolism
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STAT3 Transcription Factor
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TYK2 Kinase
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Thrombopoietin / metabolism*
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Trans-Activators / metabolism*
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Tyrosine / metabolism
Substances
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DNA-Binding Proteins
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Platelet Aggregation Inhibitors
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Proteins
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Proto-Oncogene Proteins
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Receptors, Immunologic
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Recombinant Fusion Proteins
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STAT3 Transcription Factor
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STAT3 protein, human
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Trans-Activators
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Tyrosine
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Thrombopoietin
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Protein-Tyrosine Kinases
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JAK2 protein, human
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Janus Kinase 2
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TYK2 Kinase
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TYK2 protein, human
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Aspirin