Thrombopoietin and its receptor.
Thrombopoietin (TPO), the primary physiological regulator of platelet production, was initially thought to be a lineage-specific factor acting predominantly on megakaryocytopoiesis. Detailed studies establish that this cytokine mediates biological effects on a broad spectrum of hematopoietic progenitor cells, including stem cells. TPO is a hormone constitutively produced mainly by the liver and kidney. Plasma TPO levels are regulated by the platelet and megakaryocyte mass through Mpl receptor binding, internalization and degradation. The Mpl receptor is a member of the hematopoietin receptor superfamily lacking intrinsic kinase activity. Upon ligand-induced Mpl homodimerization, the major signaling events for proliferation are mediated through the JAK2/STAT5 pathway, while differentiation might occur through a prolonged activation of the MAPK pathway. Preclinical and clinical studies demonstrate the potential use of TPO in a variety of contexts, but it is too early to evaluate its benefit in reducing platelet transfusion.
Wendling
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F
INSERM U. 362, Institut Gustave-Roussy, Villejuif, France. frog@igr.fr
Vainchenker
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D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism; D006410:Hematopoiesis / Q000502:physiology*; D006801:Humans; D053614:Janus Kinase 2; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008533:Megakaryocytes / Q000502:physiology*; D008894:Milk Proteins; D009363:Neoplasm Proteins; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D013926:Thrombopoietin / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism
D004268:DNA-Binding Proteins; D008894:Milk Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; C082218:MPL protein, human; D013926:Thrombopoietin; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases