Description
Product Characteristics:
Thrombopoietin (TPO or THPO), also known as c-Mpl ligand (c-Mpl L), is a cytokine that plays a central role in megakaryopoiesis by influencing the development and maturation of megakaryocytes and platelet production from hematopoietic stem cells. TPO exerts its biological effects through the TPO receptor, c-Mpl. c-Mpl is a member of the cytokine receptor superfamily. Expression of c-Mpl is restricted to hematopoietic tissues and cells, such as bone marrow, spleen, fetal liver and CD34+ cells. Stimulation of c-Mpl with TPO results in the activation of the Janus tyrosine kinase family members, Tyk 2 and JAK2, which in turn phosphorylate Stat5 and Stat3, causing their nuclear translocation and the transcription of Stat responsive genes. Muta-tions in c-Mpl have been implicated as the cause of certain human disorders, including congenital amegakaryocytic thrombocytopenia (CAMT) and thrombocytopenia with absent radii (TAR) syndrome.
Subcellular location: Cell membrane
Synonyms: C MPL, C-MPL, CMPL, CD110, CD 110, MPL, MPLV, Myeloprolerative leukemia protein, Myeloprolerative leukemia virus oncogene, Proto-oncogene c-Mpl, THCYT2, Thrombopoietin receptor, TPO R, TPO-R, TPOR, TPOR_HUMAN.
Target Information: In 1990 an oncogene, v-mpl, was identified from the murine myeloproliferative leukemia virus that was capable of immortalizing bone marrow hematopoietic cells from different lineages. In 1992 the human homologue, named, c-mpl, was cloned. Sequence data revealed that c-mpl encoded a protein that was homologous with members of the hematopoietic receptor superfamily. Presence of anti-sense oligodeoxynucleotides of c-mpl inhibited megakaryocyte colony formation. The ligand for c-mpl, thrombopoietin, was cloned in 1994. Thrombopoietin was shown to be the major regulator of megakaryocytopoiesis and platelet formation. The protein encoded by the c-mpl gene, CD110, is a 635 amino acid transmembrane domain, with two extracellular cytokine receptor domains and two intracellular cytokine receptor box motifs. TPO-R deficient mice were severely thrombocytopenic, emphasizing the important role of CD110 and thrombopoietin in megakaryocyte and platelet formation. Upon binding of thrombopoietin CD110 is dimerized and the JAK family of non-receptor tyrosine kinases, as well as the STAT family, the MAPK family, the adaptor protein Shc and the receptors themselves become tyrosine phosphorylated. [provided by RefSeq, Jul 2008]