THROMBOPOIETIN POTENTIATES ACTIVATION OF HUMAN PLATELETS IN ASSOCIATION WITH JAK2 AND TYK2 PHOSPHORYLATION

摘要: Thrombopoietin (TPO), also known as the c-mpl ligand, stimulates rapid tyrosine phosphorylation of multiple proteins in human platelets including Janus family kinases JAK2 and TYK2. On its own, TPO has no effect on platelet aggregation dense-granule secretion but induces a general potentiation these responses by other stimuli. The most dramatic is observed against threshold concentrations agonists for aggregation. Shape change or weak reversible induced low thrombin, collagen thromboxane mimetic, U46619, are converted into irreversible presence TPO. A similar result obtained ADP scavenger apyrase cyclo-oxygenase inhibitor indomethacin. measured through release 5-hydroxy[3H]-tryptamine. This striking stimuli independent it chelation extracellular Ca2+ with EGTA. potentiates activation phospholipase C elevation intracellular Ca2+, providing molecular explanation functional responses. may have an important physiological role priming thrombocytopenia, action that help to compensate reduced density.