Thrombopoietin (TPO) was shown to be the major regulator of megakaryocytopoiesis and platelet formation. Its receptor (TpoR aka CD110 or c-mpl) is homologous with members of the hematopoietic receptor superfamily, and has two extracellular cytokine receptor domains and two intracellular cytokine receptor box motifs. It can be found found on megakaryocyte precursor cells megakaryocytes, and platelets, as well on stem cells and early bone marrow progenitor cells of all lineage. TPO affects late maturation only of megakaryocytes and platelets but is required to maintain the viability of stem cells and precursors of all lineages. Upon binding to thrombopoietin, the receptor undergoes dimerization that results in a number of signal transduction events (JAK/STAT, and MAPK signaling pathway, among other pathways) that prevent apoptosis, improve cell viability, promote growth, and possibly increase differentiation. In addition, binding to the receptor provides the major mechanism by which thrombopoietin is removed from the circulation by platelets and possibly megakaryocytes.
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