The thrombopoietin receptor

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The biology of thrombopoietin and thrombopoietin receptor agonists.

Thrombopoietin (TPO) is the major physiological regulator of platelet production. TPO binds the TPO receptor, activates JAK and STAT pathways, thus stimulating megakaryocyte growth and platelet production. There is no "sensor" of the platelet count; rather TPO is produced in the liver at a constant rate and cleared by TPO receptors on platelets. TPO levels are inversely proportional to the rate...

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The thrombopoietin receptor P106L mutation functionally separates receptor signaling activity from thrombopoietin homeostasis.

The interaction between thrombopoietin (THPO) and its receptor c-Mpl regulates downstream cytokine signaling and platelet homeostasis. Hereditary mutations of c-Mpl can either result in loss-of-function and thrombocytopenia or in gain-of-function and thrombocythemia (HT), and are important models to analyze the mechanism of c-Mpl activity. We have analyzed the effect of the c-Mpl P106L gain-of-...

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Clinical indications for thrombopoietin and thrombopoietin-receptor agonists.

Thrombocytopenia is a common hematologic disorder. Stimulation of thrombopoiesis may reduce the risk for thrombocytopenia-induced bleeding, prevent severe thrombocytopenia, and reduce the need for platelet transfusion. The key cytokine is thrombopoietin (TPO). It regulates proliferation and maturation of megakaryocytes as well as platelet production. TPO is synthesized in the liver. Development...

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Orientation-specific signalling by thrombopoietin receptor dimers.

Ligand binding to the thrombopoietin receptor is thought to stabilize an active receptor dimer that regulates megakaryocyte differentiation and platelet formation, as well as haematopoietic stem cell renewal. By fusing a dimeric coiled coil in all seven possible orientations to the thrombopoietin receptor transmembrane (TM)-cytoplasmic domains, we show that specific biological effects and in vi...

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Posttranslational Processing of the Thrombopoietin Receptor Is Impaired in Polycythemia

Recently, we demonstrated a marked reduction in the expression of the thrombopoietin receptor, Mpl, in polycythemia vera (PV) platelets and megakaryocytes using an antiserum against the Mpl extracellular domain. To further examine this abnormality, we raised an antibody to the Mpl Cterminus. Immunologic analysis of PV platelets with this antiserum confirmed the reduction in Mpl expression. Howe...

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ژورنال

عنوان ژورنال: Japanese Journal of Thrombosis and Hemostasis

سال: 2015

ISSN: 0915-7441,1880-8808

DOI: 10.2491/jjsth.26.35