Thrombopoietin: the primary regulator of megakaryocyte and platelet production.
The development of blood cells requires the interplay of hematopoietic stem and progenitor cells, marrow stroma and polypeptide growth factors. Although many proteins support the expansion of megakaryocytic precursor cells, identification of the late acting, lineage specific growth factor for platelet production, termed thrombopoietin, has remained elusive. Recently, characterization of the proto-oncogene c-mpl revealed structural homology with the hematopoietic cytokine receptor family. Based on the cell of origin of its cDNA, we hypothesized that the ligand for c-Mpl might be identical with Tpo, and together with scientists at ZymoGenetics, Inc. recently cloned its cDNA. Using recombinant protein we have shown that the mpl-ligand displays all of the expected biological properties of the major regulator of megakaryocyte development, and proposed that it be termed thrombopoietin.
Kaushansky
K
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Division of Hematology, University of Washington, Seattle 98195, USA.
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D001792:Blood Platelets / Q000166:cytology*; D002454:Cell Differentiation / Q000502:physiology; D002986:Clinical Trials as Topic; D003001:Cloning, Molecular; D004353:Drug Evaluation, Preclinical; D005544:Forecasting; D006487:Hemostasis / Q000502:physiology*; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology*; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D011832:Radiation Injuries / Q000628:therapy; D011878:Radiotherapy / Q000009:adverse effects; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D013921:Thrombocytopenia / Q000209:etiology / Q000628:therapy; D013926:Thrombopoietin / Q000502:physiology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D013926:Thrombopoietin