Thrombopoietin receptor

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search
MPL
Identifiers
AliasesMPL, C-CD110, MPLV, THCYT2, TPOR, MPL proto-oncogene, thrombopoietin receptor, THPOR
External IDsOMIM: 159530 MGI: 97076 HomoloGene: 7845 GeneCards: MPL
Gene location (Human)
Chromosome 1 (human)
Chr.Chromosome 1 (human)[1]
Chromosome 1 (human)
Genomic location for MPL
Genomic location for MPL
Band1p34.2Start43,337,818 bp[1]
End43,354,466 bp[1]
RNA expression pattern
PBB GE MPL 207550 at fs.png

PBB GE MPL 211903 s at fs.png

PBB GE MPL 216825 s at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_005373

NM_001122949
NM_001285496
NM_001285497
NM_010823

RefSeq (protein)

NP_005364

NP_001116421
NP_001272425
NP_001272426
NP_034953

Location (UCSC)Chr 1: 43.34 – 43.35 MbChr 4: 118.44 – 118.46 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

The thrombopoietin receptor also known as the myeloproliferative leukemia protein or CD110 (Cluster of Differentiation 110) is a protein that in humans is encoded by the MPL (myeloproliferative leukemia virus) oncogene.[5]

Discovery[edit]

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 oligodeoxynucleotidesu of c-mpl inhibited megakaryocyte colony formation.

Function[edit]

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]

Interactions[edit]

Myeloproliferative leukemia virus oncogene has been shown to interact with:

Clinical relevance[edit]

Inactivating mutations in this gene have been shown to cause familial aplastic anemia.[9]

Specific mutations to this gene are associated with myelofibrosis and essential 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 abnormal megakaryocytes.[11]

See also[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000117400 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000006389 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b "Entrez Gene: MPL myeloproliferative leukemia virus oncogene".
  6. ^ Meunier C, Bordereaux D, Porteu F, Gisselbrecht S, Chrétien S, Courtois G (Mar 2002). "Cloning and characterization of a family of proteins associated with Mpl". J. Biol. Chem. 277 (11): 9139–47. doi:10.1074/jbc.M105970200. PMID 11784712.
  7. ^ Bellido M, Te Boekhorst PA (2012). "JAK2 Inhibition: Reviewing a New Therapeutical Option in Myeloproliferative Neoplasms". Adv Hematol. 2012: 535709. doi:10.1155/2012/535709. PMC 3286888. PMID 22400031.
  8. ^ Nakaya Y, Shide K, Niwa T, Homan J, Sugahara S, Horio T, Kuramoto K, Kotera T, Shibayama H, Hori K, Naito H, Shimoda K (2011). "Efficacy of NS-018, a potent and selective JAK2/Src inhibitor, in primary cells and mouse models of myeloproliferative neoplasms". Blood Cancer J. 1 (7): e29. doi:10.1038/bcj.2011.29. PMC 3255248. PMID 22829185.
  9. ^ Walne AJ, Dokal A, Plagnol V, Beswick R, Kirwan M, de la Fuente J, Vulliamy T, Dokal I (December 2011). "Exome sequencing identifies MPL as a causative gene in familial aplastic anemia". Haematologica. 97 (4): 524–8. doi:10.3324/haematol.2011.052787. PMC 3347658. PMID 22180433.
  10. ^ Tefferi, A; Lasho, T L; Finke, C M; Knudson, R A; Ketterling, R; Hanson, C H; Maffioli, M; Caramazza, D; Passamonti, F; Pardanani, A (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. ISSN 0887-6924. PMID 24402162.
  11. ^ Tefferi, A (2010). "Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1". Leukemia. 24 (6): 1128–1138. doi:10.1038/leu.2010.69. ISSN 0887-6924. PMC 3035972. PMID 20428194.

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.