Receptor da trombopoetina

O oncoxene do virus da leucemia mieloproliferativa (MPL) tamén chamado xene do CD110 (Cluster of Differentiation 110) ou xene do receptor da trombopoetina^[1], é un xene humano que se encontra no cromosoma 1.^[2]

Penciolelli et al. en 1987 identificaron un retrovirus defectivo de ratos que causaba neses animais leucemia aguda, polo que se lle deu o nome de "virus da leucemia mieloproliferativa" (MPLV)^[1][3]. En 1990 identificouse o oncoxene v-mpl a partir do virus da leucemia mieloproliferativa murina, que podía inmortalizar as células hematopoéticas da medula ósea de diferentes liñaxes. En 1992 clonouse o xene homólogo humano chamado c-mpl. Os datos da súa secuencia revelaron que o c-mpl codificaba unha proteína que era homóloga a membros da superfamilia do receptor hematopoético. A presenza de oligodesoxinucleótidos antisentido do c-mpl inhibía a formación de colonias de megacariocitos. O ligando do c-mpl é a trombopoetina, que se clonou en 1994. A trombopoetina é o principal regulador da megacariocitopoese e da formación de plaquetas. A proteína codificada polo xene c-mpl é o CD110, que ten un dominio transmembrana de 635 aminoácidos, e dous dominios receptores de citocinas extracelulares e dúas caixas motivos receptoras de citocinas intracelulares. Os ratos deficientes TPO-R sofren unha grave trombocitopenia (escaseza de plaquetas), o que salienta a importancia do CD110 e da trombopoetina na formación de megacariocitos e plaquetas. Unha vez que se une a trombopoetina ao CD110, este dimerízase e a familia JAK de tirosina quinases non receptoras, e a familia STAT, a familia MAPK, a proteína adaptadora Shc e os propios receptores son fosforiladas na tirosina.^[2]

Interaccións

O oncoxene do virus da leucemia mieloproliferativa presenta interaccións con ATXN2L.^[4]

Importancia clínica

As mutacións neste xene causan a anemia aplástica familiar.^[5]

Notas

1. OMIM MPL
2. "Entrez Gene: MPL myeloproliferative leukemia virus oncogene". 
3. Penciolelli, J. F., Wendling, F., Robert-Lezenes, J., Barque, J. F., Tambourin, P., Gisselbrecht, S. Genetic analysis of myeloproliferative leukemia virus, a novel acute leukemogenic replication-defective retrovirus. J. Virol. 61: 579-583, 1987. PMID 3027384.
4. Meunier, Caroline; Bordereaux Didier, Porteu Francoise, Gisselbrecht Sylvie, Chrétien Stany, Courtois Geneviève (2002). "Cloning and characterization of a family of proteins associated with Mpl". J. Biol. Chem. (United States) 277 (11): 9139–47. ISSN 0021-9258. PMID 11784712. doi:10.1074/jbc.M105970200. 
5. Walne A, Dokal A, Plagnol V, Beswick R, Kirwan M, de la Fuente J, Vulliamy T, Dokal I (2011). "Exome sequencing identifies MPL as a causative gene in familial aplastic anemia". Haematologica 97 (4): 524–8. PMC 3347658. PMID 22180433. doi:10.3324/haematol.2011.052787. 

Véxase tamén

Bibliografía

• Kato T, Matsumoto A, Ogami K; et al. (1999). "Native thrombopoietin: structure and function.". Stem Cells 16 (5): 322–8. PMID 9766811. doi:10.1002/stem.160322. 
• Vigon I, Mornon JP, Cocault L; et al. (1992). "Molecular cloning and characterization of MPL, the human homolog of the v-mpl oncogene: identification of a member of the hematopoietic growth factor receptor superfamily.". Proc. Natl. Acad. Sci. U.S.A. 89 (12): 5640–4. PMC 49348. PMID 1608974. doi:10.1073/pnas.89.12.5640. 
• Souyri M, Vigon I, Penciolelli JF; et al. (1991). "A putative truncated cytokine receptor gene transduced by the myeloproliferative leukemia virus immortalizes hematopoietic progenitors.". Cell 63 (6): 1137–47. PMID 2175677. doi:10.1016/0092-8674(90)90410-G. 
• Le Coniat M, Souyri M, Vigon I; et al. (1989). "The human homolog of the myeloproliferative virus maps to chromosome band 1p34.". Hum. Genet. 83 (2): 194–6. PMID 2550356. doi:10.1007/BF00286717. 
• Drachman JG, Griffin JD, Kaushansky K (1995). "The c-Mpl ligand (thrombopoietin) stimulates tyrosine phosphorylation of Jak2, Shc, and c-Mpl.". J. Biol. Chem. 270 (10): 4979–82. PMID 7534285. doi:10.1074/jbc.270.10.4979. 
• Mignotte V, Vigon I, Boucher de Crèvecoeur E; et al. (1994). "Structure and transcription of the human c-mpl gene (MPL).". Genomics 20 (1): 5–12. PMID 8020956. doi:10.1006/geno.1994.1120. 
• Mu SX, Xia M, Elliott G; et al. (1996). "Megakaryocyte growth and development factor and interleukin-3 induce patterns of protein-tyrosine phosphorylation that correlate with dominant differentiation over proliferation of mpl-transfected 32D cells.". Blood 86 (12): 4532–43. PMID 8541543. 
• Deveaux S, Filipe A, Lemarchandel V; et al. (1996). "Analysis of the thrombopoietin receptor (MPL) promoter implicates GATA and Ets proteins in the coregulation of megakaryocyte-specific genes.". Blood 87 (11): 4678–85. PMID 8639837. 
• Drachman JG, Kaushansky K (1997). "Dissecting the thrombopoietin receptor: functional elements of the Mpl cytoplasmic domain.". Proc. Natl. Acad. Sci. U.S.A. 94 (6): 2350–5. PMC 20091. PMID 9122198. doi:10.1073/pnas.94.6.2350. 
• Ihara K, Ishii E, Eguchi M; et al. (1999). "Identification of mutations in the c-mpl gene in congenital amegakaryocytic thrombocytopenia.". Proc. Natl. Acad. Sci. U.S.A. 96 (6): 3132–6. PMC 15907. PMID 10077649. doi:10.1073/pnas.96.6.3132. 
• Drachman JG, Millett KM, Kaushansky K (1999). "Thrombopoietin signal transduction requires functional JAK2, not TYK2.". J. Biol. Chem. 274 (19): 13480–4. PMID 10224114. doi:10.1074/jbc.274.19.13480. 
• Cargill M, Altshuler D, Ireland J; et al. (1999). "Characterization of single-nucleotide polymorphisms in coding regions of human genes.". Nat. Genet. 22 (3): 231–8. PMID 10391209. doi:10.1038/10290. 
• Okabe S, Tauchi T, Morita H; et al. (1999). "Thrombopoietin induces an SH2-containing protein, CIS1, which binds to Mpl: involvement of the ubiquitin proteosome pathway.". Exp. Hematol. 27 (10): 1542–7. PMID 10517496. doi:10.1016/S0301-472X(99)00094-6. 
• Miyakawa Y, Drachman JG, Gallis B; et al. (2000). "A structure-function analysis of serine/threonine phosphorylation of the thrombopoietin receptor, c-Mpl.". J. Biol. Chem. 275 (41): 32214–9. PMID 10918061. doi:10.1074/jbc.M005080200. 
• van den Oudenrijn S, Bruin M, Folman CC; et al. (2000). "Mutations in the thrombopoietin receptor, Mpl, in children with congenital amegakaryocytic thrombocytopenia.". Br. J. Haematol. 110 (2): 441–8. PMID 10971406. doi:10.1046/j.1365-2141.2000.02175.x. 
• Wang Q, Miyakawa Y, Fox N, Kaushansky K (2000). "Interferon-alpha directly represses megakaryopoiesis by inhibiting thrombopoietin-induced signaling through induction of SOCS-1.". Blood 96 (6): 2093–9. PMID 10979953. 
• Miyakawa Y, Rojnuckarin P, Habib T, Kaushansky K (2001). "Thrombopoietin induces phosphoinositol 3-kinase activation through SHP2, Gab, and insulin receptor substrate proteins in BAF3 cells and primary murine megakaryocytes.". J. Biol. Chem. 276 (4): 2494–502. PMID 11054408. doi:10.1074/jbc.M002633200. 
• Tonelli R, Scardovi AL, Pession A; et al. (2000). "Compound heterozygosity for two different amino-acid substitution mutations in the thrombopoietin receptor (c-mpl gene) in congenital amegakaryocytic thrombocytopenia (CAMT).". Hum. Genet. 107 (3): 225–33. PMID 11071383. doi:10.1007/s004390000357. 
• Ballmaier M, Germeshausen M, Schulze H; et al. (2001). "c-mpl mutations are the cause of congenital amegakaryocytic thrombocytopenia.". Blood 97 (1): 139–46. PMID 11133753. doi:10.1182/blood.V97.1.139. 

Ligazóns externas

• MeshName MPL+protein,+human [1]