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

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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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Running title: c-Mpl P106L receptor processing and activation Category: Platelets and thrombopoiesis 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 and are important models to analyze the mechanism of c-Mpl activity. We have analyzed the effect of the c-Mpl P106L gain-of-functi...

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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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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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ژورنال

عنوان ژورنال: Blood

سال: 2015

ISSN: 0006-4971,1528-0020

DOI: 10.1182/blood-2014-07-587170