Ubiquitination and degradation of the thrombopoietin receptor c-Mpl

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Ubiquitination and degradation of the thrombopoietin receptor c-Mpl.

Regulation of growth factor and cytokine signaling is essential for maintaining physiologic numbers of circulating hematopoietic cells. Thrombopoietin (Tpo), acting through its receptor c-Mpl, is required for hematopoietic stem cell maintenance and megakaryopoiesis. Therefore, the negative regulation of Tpo signaling is critical in many aspects of hematopoiesis. In this study, we determine the ...

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Modulation of megakaryocytopoiesis by thrombopoietin: the c-Mpl ligand.

We have further characterized the biological activities, mechanism of action, and target cell populations of recombinant human and murine thrombopoietin (rhTPO and rmTPO) in in vitro human and murine model systems. Alone, hTPO or mTPO stimulated the maturation of immature murine megakaryoblasts as measured in a single cell assay. The combination of hTPO or mTPO and interleukin-6 (IL-6) resulted...

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Hematopoietic stem cell deficiencies in mice lacking c-Mpl, the receptor for thrombopoietin.

Thrombopoietin (TPO) acts as a lineage-specific late-acting factor to stimulate megakaryocyte and platelet formation. However, analysis of mice lacking either the cytokine or its receptor, c-Mpl, also revealed deficiencies in progenitor cells of multiple hematopoietic lineages, suggesting that TPO signaling may play an important role in the regulation of the hematopoietic stem cell compartment....

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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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Molecular detection of c-mpl thrombopoietin receptor gene expression in chronic myeloproliferative disorders.

BACKGROUND Chronic myeloproliferative disorders (CMPD) originate from a pluripotent haematopoietic progenitor cell but show a marked degree of heterogeneity, especially between Philadelphia chromosome positive and negative disease entities. Abnormal megakaryopoiesis is a frequent finding in CMPD, often associated with thrombocythaemic cell counts. Recent experimental data have suggested that th...

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ژورنال

عنوان ژورنال: Blood

سال: 2010

ISSN: 0006-4971,1528-0020

DOI: 10.1182/blood-2009-06-227033