Thethrombopoietin receptor also known as themyeloproliferative leukemia protein orCD110 (Cluster ofDifferentiation110) is aprotein that in humans is encoded by theMPL (myeloproliferative leukemia virus)oncogene.[5]
In 1990 an oncogene, v-mpl, was identified from the murine myeloproliferativeleukemia virus that was capable of immortalizing bone marrowhematopoietic cells from different lineages. In 1992 the humanhomologue, named, c-mpl, was cloned. Sequence data revealed that c-mpl encoded a protein that was homologous with members of the hematopoietic receptorsuperfamily. 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.[5]
Inactivating mutations in this gene have been shown to cause familialaplastic anemia.[9]
Specific mutations to this gene are associated withmyelofibrosis andessential thrombocythemia.[10] In essential thrombocythemia, mutations occur at position 505 or 515 in the protein. In myelofibrosis, a mutation occurs at position 515. These mutations lead to the production of thrombopoietin receptors that are permanently activated, which results in the overproduction of abnormalmegakaryocytes.[11]
^Tefferi A, Lasho TL, Finke CM, Knudson RA, Ketterling R, Hanson CH, et al. (July 2014). "CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons".Leukemia.28 (7):1472–1477.doi:10.1038/leu.2014.3.PMID24402162.S2CID52852665.
Souyri M, Vigon I, Penciolelli JF, Heard JM, Tambourin P, Wendling F (December 1990). "A putative truncated cytokine receptor gene transduced by the myeloproliferative leukemia virus immortalizes hematopoietic progenitors".Cell.63 (6):1137–1147.doi:10.1016/0092-8674(90)90410-G.PMID2175677.S2CID7946220.
Le Coniat M, Souyri M, Vigon I, Wendling F, Tambourin P, Berger R (September 1989). "The human homolog of the myeloproliferative virus maps to chromosome band 1p34".Human Genetics.83 (2):194–196.doi:10.1007/BF00286717.PMID2550356.S2CID20970372.
Mignotte V, Vigon I, Boucher de Crèvecoeur E, Roméo PH, Lemarchandel V, Chrétien S (March 1994). "Structure and transcription of the human c-mpl gene (MPL)".Genomics.20 (1):5–12.doi:10.1006/geno.1994.1120.PMID8020956.
Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, et al. (July 1999). "Characterization of single-nucleotide polymorphisms in coding regions of human genes".Nature Genetics.22 (3):231–238.doi:10.1038/10290.PMID10391209.S2CID195213008.
Wang Q, Miyakawa Y, Fox N, Kaushansky K (September 2000). "Interferon-alpha directly represses megakaryopoiesis by inhibiting thrombopoietin-induced signaling through induction of SOCS-1".Blood.96 (6):2093–2099.doi:10.1182/blood.V96.6.2093.PMID10979953.
Tonelli R, Scardovi AL, Pession A, Strippoli P, Bonsi L, Vitale L, et al. (September 2000). "Compound heterozygosity for two different amino-acid substitution mutations in the thrombopoietin receptor (c-mpl gene) in congenital amegakaryocytic thrombocytopenia (CAMT)".Human Genetics.107 (3):225–233.doi:10.1007/s004390000357.PMID11071383.S2CID10211260.
