Quinase Xano 2

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JAK2
Protein JAK2 PDB 2b7a.png
Estruturas dispoñibles
PDBBuscar ortólogos: PDBe, RCSB
Identificadores
SímbolosJAK2 (HGNC: 6192) JTK10, THCYT3, Janus kinase 2, MAX2
Identificadores
externos
LocusCr. 9 p24.1
Ortólogos
Especies
Humano Rato
Entrez
3717 16452
Ensembl
Véxase HS Véxase MM
UniProt
O60674 Q62120
RefSeq
(ARNm)
NM_004972 NM_001048177
RefSeq
(proteína) NCBI
NP_001309123 NP_001041642
Localización (UCSC)
Cr. 9:
4.98 – 5.13 Mb
Cr. 19:
29.25 – 29.31 Mb
PubMed (Busca)
3717


16452

A quinase Xano 2 (abreviada comunmente como JAK2, do inglés Janus kinase 2) é unha tirosina quinase non receptora. É un membro da familia da quinase Xano, nome que lle foi dado polo deus latino Xano, pola dualidade de funcións dos seus dominios, análoga á dese deus de dúas caras. Foi implicada na sinalización por membros da familia do receptor de citocina de tipo II (por exemplo, receptores de interferón), da familia do receptor de GM-CSF (IL-3R, IL-5R e GM-CSF-R), da familia do receptor de gp130 (por exemplo, IL-6R), e dos receptores de cadea simple (por exemplo, Epo-R, Tpo-R, GH-R, PRL-R).[1][2]

A característica distintiva entre a quinase Xano 2 e outras quinases JAK é a falta de dominios de unión de homoloxía Src (SH2/SH3) e a presenza de ata sete dominios de homoloxía JAK (JH1-JH7). Non obstante, os dominios JH terminais manteñen un alto nivel de homoloxía con dominios de tirosina quinases. Unha nota interesante é que só un deses dominios JH carboxilo terminais manteñen a función plena de quinase (o JH1), mentres que o outro (o JH2), que antes se pensaba que non tiña funcionalidade de quinase e, en consecuencia, foi nomeado dominio pseudoquinase, atopouse despois que era tamén cataliticamente activo, pero só a un 10% do nivel do dominio JH1.[3][4]

A perda de Jak2 é letal para os ratos de 12 días embrionarios.[5]

Os ortólogos de JAK2[6] foron identificados en todos os mamíferos dos cales se dispón de datos xenómicos completos.

Importancia clínica[editar | editar a fonte]

Observáronse fusións do xene JAK2 con TEL(ETV6) (TEL-JAK2) e xenes PCM1 en pacientes de leucemia, especialmente nas formas con eosinofilia clonal desa doenza.[7][8][9]

As mutacións en JAK2 foron implicadas na policitemia vera, na trombocitocitemia esencial e na mielofibrose, así como noutros trastornos mieloproliferativos.[10] Esta mutación (V617F), que é un cambio de valina a fenilalanina na posición 617, parece facer que as células hematopoéticas sexan máis sensibles a factores de crecemento, como a eritropoetina e a trombopoetina, porque os receptores para estes factores de crecemento requiren JAK2 para a transdución de sinais. Atopouse que un inhibidor de JAK2-STAT5, o AZD1480, tiña actividade en certos cancros de próstata.[11] A mutación en Jak2, cando é demostrable, é un dos métodos de diagnose da policitemia vera.[12]

Interaccións[editar | editar a fonte]

A quinase Xano 2 presenta interaccións con:

A prolactina envía sinais a través de JAK2 de modo dependente de STAT5, e de factores de transdución RUSH.[56]

Notas[editar | editar a fonte]

  1. Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA (June 1998). "Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice". Endocrine Reviews 19 (3): 225–68. PMID 9626554. doi:10.1210/er.19.3.225. 
  2. Brooks AJ, Dai W, O'Mara ML, Abankwa D, Chhabra Y, Pelekanos RA, et al. (2014). "Mechanism of activation of protein kinase JAK2 by the growth hormone receptor". Science 344 (6185): 1249783. PMID 24833397. doi:10.1126/science.1249783. 
  3. Morgan KJ, Gilliland DG (2008). "A role for JAK2 mutations in myeloproliferative diseases". Annual Review of Medicine 59 (1): 213–22. PMID 17919086. doi:10.1146/annurev.med.59.061506.154159. 
  4. Ungureanu D, Wu J, Pekkala T, Niranjan Y, Young C, Jensen ON, Xu CF, Neubert TA, Skoda RC, Hubbard SR, Silvennoinen O (August 2011). "The pseudokinase domain of JAK2 is a dual-specificity protein kinase that negatively regulates cytokine signaling". Nature Structural & Molecular Biology 18 (9): 971–976. PMC 4504201. PMID 21841788. doi:10.1038/nsmb.2099. 
  5. Neubauer H, Cumano A, Müller M, Wu H, Huffstadt U, Pfeffer K (May 1998). "Jak2 deficiency defines an essential developmental checkpoint in definitive hematopoiesis". Cell 93 (3): 397–409. PMID 9590174. doi:10.1016/S0092-8674(00)81168-X. 
  6. "OrthoMaM phylogenetic marker: JAK2 coding sequence". [Ligazón morta]
  7. Lacronique V, Boureux A, Valle VD, Poirel H, Quang CT, Mauchauffé M, Berthou C, Lessard M, Berger R, Ghysdael J, Bernard OA (November 1997). "A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia". Science 278 (5341): 1309–12. PMID 9360930. doi:10.1126/science.278.5341.1309. 
  8. Reiter A, Walz C, Watmore A, Schoch C, Blau I, Schlegelberger B, Berger U, Telford N, Aruliah S, Yin JA, Vanstraelen D, Barker HF, Taylor PC, O'Driscoll A, Benedetti F, Rudolph C, Kolb HJ, Hochhaus A, Hehlmann R, Chase A, Cross NC (April 2005). "The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2". Cancer Research 65 (7): 2662–7. PMID 15805263. doi:10.1158/0008-5472.CAN-04-4263. 
  9. Reiter A, Gotlib J (2017). "Myeloid neoplasms with eosinophilia". Blood 129 (6): 704–714. PMID 28028030. doi:10.1182/blood-2016-10-695973. 
  10. Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, Tichelli A, Cazzola M, Skoda RC (April 2005). "A gain-of-function mutation of JAK2 in myeloproliferative disorders". The New England Journal of Medicine 352 (17): 1779–90. PMID 15858187. doi:10.1056/NEJMoa051113. 
  11. Gu L, Liao Z, Hoang DT, Dagvadorj A, Gupta S, Blackmon S, Ellsworth E, Talati P, Leiby B, Zinda M, Lallas CD, Trabulsi EJ, McCue P, Gomella L, Huszar D, Nevalainen MT (October 2013). "Pharmacologic inhibition of Jak2-Stat5 signaling By Jak2 inhibitor AZD1480 potently suppresses growth of both primary and castrate-resistant prostate cancer". Clinical Cancer Research 19 (20): 5658–74. PMID 23942095. doi:10.1158/1078-0432.CCR-13-0422. 
  12. Scott LM (August 2011). "The JAK2 exon 12 mutations: a comprehensive review". American Journal of Hematology 86 (8): 668–76. PMID 21674578. doi:10.1002/ajh.22063. 
  13. Sarkar S, Pollack BP, Lin KT, Kotenko SV, Cook JR, Lewis A, Pestka S (December 2001). "hTid-1, a human DnaJ protein, modulates the interferon signaling pathway". The Journal of Biological Chemistry 276 (52): 49034–42. PMID 11679576. doi:10.1074/jbc.M103683200. 
  14. Olayioye MA, Beuvink I, Horsch K, Daly JM, Hynes NE (June 1999). "ErbB receptor-induced activation of stat transcription factors is mediated by Src tyrosine kinases". The Journal of Biological Chemistry 274 (24): 17209–18. PMID 10358079. doi:10.1074/jbc.274.24.17209. 
  15. Huang LJ, Constantinescu SN, Lodish HF (December 2001). "The N-terminal domain of Janus kinase 2 is required for Golgi processing and cell surface expression of erythropoietin receptor". Molecular Cell 8 (6): 1327–38. PMID 11779507. doi:10.1016/S1097-2765(01)00401-4. 
  16. Witthuhn BA, Quelle FW, Silvennoinen O, Yi T, Tang B, Miura O, Ihle JN (July 1993). "JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin". Cell 74 (2): 227–36. PMID 8343951. doi:10.1016/0092-8674(93)90414-L. 
  17. Sayeski PP, Ali MS, Safavi A, Lyles M, Kim SO, Frank SJ, Bernstein KE (November 1999). "A catalytically active Jak2 is required for the angiotensin II-dependent activation of Fyn". The Journal of Biological Chemistry 274 (46): 33131–42. PMID 10551884. doi:10.1074/jbc.274.46.33131. 
  18. Chauhan D, Kharbanda SM, Ogata A, Urashima M, Frank D, Malik N, Kufe DW, Anderson KC (December 1995). "Oncostatin M induces association of Grb2 with Janus kinase JAK2 in multiple myeloma cells". The Journal of Experimental Medicine 182 (6): 1801–6. PMC 2192257. PMID 7500025. doi:10.1084/jem.182.6.1801. 
  19. Giorgetti-Peraldi S, Peyrade F, Baron V, Van Obberghen E (December 1995). "Involvement of Janus kinases in the insulin signaling pathway". European Journal of Biochemistry / FEBS 234 (2): 656–60. PMID 8536716. doi:10.1111/j.1432-1033.1995.656_b.x. 
  20. Frank SJ, Yi W, Zhao Y, Goldsmith JF, Gilliland G, Jiang J, Sakai I, Kraft AS (June 1995). "Regions of the JAK2 tyrosine kinase required for coupling to the growth hormone receptor". The Journal of Biological Chemistry 270 (24): 14776–85. PMID 7540178. doi:10.1074/jbc.270.24.14776. 
  21. VanderKuur JA, Wang X, Zhang L, Campbell GS, Allevato G, Billestrup N, Norstedt G, Carter-Su C (August 1994). "Domains of the growth hormone receptor required for association and activation of JAK2 tyrosine kinase". The Journal of Biological Chemistry 269 (34): 21709–17. PMID 8063815. 
  22. Hellgren G, Jansson JO, Carlsson LM, Carlsson B (June 1999). "The growth hormone receptor associates with Jak1, Jak2 and Tyk2 in human liver". Growth Hormone & IGF Research 9 (3): 212–8. PMID 10502458. doi:10.1054/ghir.1999.0111. 
  23. Gual P, Baron V, Lequoy V, Van Obberghen E (March 1998). "Interaction of Janus kinases JAK-1 and JAK-2 with the insulin receptor and the insulin-like growth factor-1 receptor". Endocrinology 139 (3): 884–93. PMID 9492017. doi:10.1210/endo.139.3.5829. 
  24. Kawazoe Y, Naka T, Fujimoto M, Kohzaki H, Morita Y, Narazaki M, Okumura K, Saitoh H, Nakagawa R, Uchiyama Y, Akira S, Kishimoto T (January 2001). "Signal transducer and activator of transcription (STAT)-induced STAT inhibitor 1 (SSI-1)/suppressor of cytokine signaling 1 (SOCS1) inhibits insulin signal transduction pathway through modulating insulin receptor substrate 1 (IRS-1) phosphorylation". The Journal of Experimental Medicine 193 (2): 263–9. PMC 2193341. PMID 11208867. doi:10.1084/jem.193.2.263. 
  25. Yamamoto K, Shibata F, Miura O, Kamiyama R, Hirosawa S, Miyasaka N (April 1999). "Physical interaction between interleukin-12 receptor beta 2 subunit and Jak2 tyrosine kinase: Jak2 associates with cytoplasmic membrane-proximal region of interleukin-12 receptor beta 2 via amino-terminus". Biochemical and Biophysical Research Communications 257 (2): 400–4. PMID 10198225. doi:10.1006/bbrc.1999.0479. 
  26. Ogata N, Kouro T, Yamada A, Koike M, Hanai N, Ishikawa T, Takatsu K (April 1998). "JAK2 and JAK1 constitutively associate with an interleukin-5 (IL-5) receptor alpha and betac subunit, respectively, and are activated upon IL-5 stimulation". Blood 91 (7): 2264–71. PMID 9516124. 
  27. 27,0 27,1 27,2 Fuhrer DK, Yang YC (July 1996). "Complex formation of JAK2 with PP2A, P13K, and Yes in response to the hematopoietic cytokine interleukin-11". Biochemical and Biophysical Research Communications 224 (2): 289–96. PMID 8702385. doi:10.1006/bbrc.1996.1023. 
  28. Zhu T, Goh EL, Lobie PE (April 1998). "Growth hormone stimulates the tyrosine phosphorylation and association of p125 focal adhesion kinase (FAK) with JAK2. Fak is not required for stat-mediated transcription". The Journal of Biological Chemistry 273 (17): 10682–9. PMID 9553131. doi:10.1074/jbc.273.17.10682. 
  29. Ryu H, Lee JH, Kim KS, Jeong SM, Kim PH, Chung HT (August 2000). "Regulation of neutrophil adhesion by pituitary growth hormone accompanies tyrosine phosphorylation of Jak2, p125FAK, and paxillin". Journal of Immunology 165 (4): 2116–23. PMID 10925297. doi:10.4049/jimmunol.165.4.2116. 
  30. Yin T, Shen R, Feng GS, Yang YC (January 1997). "Molecular characterization of specific interactions between SHP-2 phosphatase and JAK tyrosine kinases". The Journal of Biological Chemistry 272 (2): 1032–7. PMID 8995399. doi:10.1074/jbc.272.2.1032. 
  31. Tauchi T, Damen JE, Toyama K, Feng GS, Broxmeyer HE, Krystal G (June 1996). "Tyrosine 425 within the activated erythropoietin receptor binds Syp, reduces the erythropoietin required for Syp tyrosine phosphorylation, and promotes mitogenesis". Blood 87 (11): 4495–501. PMID 8639815. 
  32. Maegawa H, Kashiwagi A, Fujita T, Ugi S, Hasegawa M, Obata T, Nishio Y, Kojima H, Hidaka H, Kikkawa R (November 1996). "SHPTP2 serves adapter protein linking between Janus kinase 2 and insulin receptor substrates". Biochemical and Biophysical Research Communications 228 (1): 122–7. PMID 8912646. doi:10.1006/bbrc.1996.1626. 
  33. Jiao H, Berrada K, Yang W, Tabrizi M, Platanias LC, Yi T (December 1996). "Direct association with and dephosphorylation of Jak2 kinase by the SH2-domain-containing protein tyrosine phosphatase SHP-1". Molecular and Cellular Biology 16 (12): 6985–92. PMC 231702. PMID 8943354. doi:10.1128/mcb.16.12.6985. 
  34. Wu DW, Stark KC, Dunnington D, Dillon SB, Yi T, Jones C, Pelus LM (February 2000). "SH2-Containing protein tyrosine phosphatase-1 (SHP-1) association with Jak2 in UT-7/Epo cells". Blood Cells, Molecules & Diseases 26 (1): 15–24. PMID 10772872. doi:10.1006/bcmd.2000.0273. 
  35. Pollack BP, Kotenko SV, He W, Izotova LS, Barnoski BL, Pestka S (October 1999). "The human homologue of the yeast proteins Skb1 and Hsl7p interacts with Jak kinases and contains protein methyltransferase activity". The Journal of Biological Chemistry 274 (44): 31531–42. PMID 10531356. doi:10.1074/jbc.274.44.31531. 
  36. Rui L, Mathews LS, Hotta K, Gustafson TA, Carter-Su C (November 1997). "Identification of SH2-Bbeta as a substrate of the tyrosine kinase JAK2 involved in growth hormone signaling". Molecular and Cellular Biology 17 (11): 6633–44. PMC 232517. PMID 9343427. doi:10.1128/mcb.17.11.6633. 
  37. Xie S, Lin H, Sun T, Arlinghaus RB (October 2002). "Jak2 is involved in c-Myc induction by Bcr-Abl". Oncogene 21 (47): 7137–46. PMID 12370803. doi:10.1038/sj.onc.1205942. 
  38. VanderKuur J, Allevato G, Billestrup N, Norstedt G, Carter-Su C (March 1995). "Growth hormone-promoted tyrosyl phosphorylation of SHC proteins and SHC association with Grb2". The Journal of Biological Chemistry 270 (13): 7587–93. PMID 7535773. doi:10.1074/jbc.270.13.7587. 
  39. Giordano V, De Falco G, Chiari R, Quinto I, Pelicci PG, Bartholomew L, Delmastro P, Gadina M, Scala G (May 1997). "Shc mediates IL-6 signaling by interacting with gp130 and Jak2 kinase". Journal of Immunology 158 (9): 4097–103. PMID 9126968. 
  40. Sasaki A, Yasukawa H, Shouda T, Kitamura T, Dikic I, Yoshimura A (September 2000). "CIS3/SOCS-3 suppresses erythropoietin (EPO) signaling by binding the EPO receptor and JAK2". The Journal of Biological Chemistry 275 (38): 29338–47. PMID 10882725. doi:10.1074/jbc.M003456200. 
  41. Sasaki A, Yasukawa H, Suzuki A, Kamizono S, Syoda T, Kinjyo I, Sasaki M, Johnston JA, Yoshimura A (June 1999). "Cytokine-inducible SH2 protein-3 (CIS3/SOCS3) inhibits Janus tyrosine kinase by binding through the N-terminal kinase inhibitory region as well as SH2 domain". Genes to Cells 4 (6): 339–51. PMID 10421843. doi:10.1046/j.1365-2443.1999.00263.x. 
  42. 42,0 42,1 Masuhara M, Sakamoto H, Matsumoto A, Suzuki R, Yasukawa H, Mitsui K, Wakioka T, Tanimura S, Sasaki A, Misawa H, Yokouchi M, Ohtsubo M, Yoshimura A (October 1997). "Cloning and characterization of novel CIS family genes". Biochemical and Biophysical Research Communications 239 (2): 439–46. PMID 9344848. doi:10.1006/bbrc.1997.7484. 
  43. 43,0 43,1 Barahmand-Pour F, Meinke A, Groner B, Decker T (May 1998). "Jak2-Stat5 interactions analyzed in yeast". The Journal of Biological Chemistry 273 (20): 12567–75. PMID 9575217. doi:10.1074/jbc.273.20.12567. 
  44. 44,0 44,1 Fujitani Y, Hibi M, Fukada T, Takahashi-Tezuka M, Yoshida H, Yamaguchi T, Sugiyama K, Yamanaka Y, Nakajima K, Hirano T (February 1997). "An alternative pathway for STAT activation that is mediated by the direct interaction between JAK and STAT". Oncogene 14 (7): 751–61. PMID 9047382. doi:10.1038/sj.onc.1200907. 
  45. Takeshita T, Arita T, Higuchi M, Asao H, Endo K, Kuroda H, Tanaka N, Murata K, Ishii N, Sugamura K (April 1997). "STAM, signal transducing adaptor molecule, is associated with Janus kinases and involved in signaling for cell growth and c-myc induction". Immunity 6 (4): 449–57. PMID 9133424. doi:10.1016/S1074-7613(00)80288-5. 
  46. Yasukawa H, Misawa H, Sakamoto H, Masuhara M, Sasaki A, Wakioka T, Ohtsuka S, Imaizumi T, Matsuda T, Ihle JN, Yoshimura A (March 1999). "The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop". The EMBO Journal 18 (5): 1309–20. PMC 1171221. PMID 10064597. doi:10.1093/emboj/18.5.1309. 
  47. Dif F, Saunier E, Demeneix B, Kelly PA, Edery M (December 2001). "Cytokine-inducible SH2-containing protein suppresses PRL signaling by binding the PRL receptor". Endocrinology 142 (12): 5286–93. PMID 11713228. doi:10.1210/endo.142.12.8549. 
  48. Endo TA, Masuhara M, Yokouchi M, Suzuki R, Sakamoto H, Mitsui K, Matsumoto A, Tanimura S, Ohtsubo M, Misawa H, Miyazaki T, Leonor N, Taniguchi T, Fujita T, Kanakura Y, Komiya S, Yoshimura A (June 1997). "A new protein containing an SH2 domain that inhibits JAK kinases". Nature 387 (6636): 921–4. PMID 9202126. doi:10.1038/43213. 
  49. Pezet A, Favre H, Kelly PA, Edery M (August 1999). "Inhibition and restoration of prolactin signal transduction by suppressors of cytokine signaling". The Journal of Biological Chemistry 274 (35): 24497–502. PMID 10455112. doi:10.1074/jbc.274.35.24497. 
  50. Ungureanu D, Saharinen P, Junttila I, Hilton DJ, Silvennoinen O (May 2002). "Regulation of Jak2 through the ubiquitin-proteasome pathway involves phosphorylation of Jak2 on Y1007 and interaction with SOCS-1". Molecular and Cellular Biology 22 (10): 3316–26. PMC 133778. PMID 11971965. doi:10.1128/MCB.22.10.3316-3326.2002. 
  51. Takahashi-Tezuka M, Hibi M, Fujitani Y, Fukada T, Yamaguchi T, Hirano T (May 1997). "Tec tyrosine kinase links the cytokine receptors to PI-3 kinase probably through JAK". Oncogene 14 (19): 2273–82. PMID 9178903. doi:10.1038/sj.onc.1201071. 
  52. Yamashita Y, Watanabe S, Miyazato A, Ohya Ki, Ikeda U, Shimada K, Komatsu N, Hatake K, Miura Y, Ozawa K, Mano H (March 1998). "Tec and Jak2 kinases cooperate to mediate cytokine-driven activation of c-fos transcription". Blood 91 (5): 1496–507. PMID 9473212. 
  53. Guo D, Dunbar JD, Yang CH, Pfeffer LM, Donner DB (March 1998). "Induction of Jak/STAT signaling by activation of the type 1 TNF receptor". Journal of Immunology 160 (6): 2742–50. PMID 9510175. 
  54. Shigematsu H, Iwasaki H, Otsuka T, Ohno Y, Arima F, Niho Y (May 1997). "Role of the vav proto-oncogene product (Vav) in erythropoietin-mediated cell proliferation and phosphatidylinositol 3-kinase activity". The Journal of Biological Chemistry 272 (22): 14334–40. PMID 9162069. doi:10.1074/jbc.272.22.14334. 
  55. "Findings of scientific misconduct". NIH Guide for Grants and Contracts / U.S. Department of Health, Education, and Welfare 24 (42): 1–2. December 1995. PMC 4259583. PMID 7495607. 
  56. Helmer RA, Panchoo M, Dertien JS, Bhakta SM, Hewetson A, Chilton BS (August 2010). "Prolactin-induced Jak2 phosphorylation of RUSH: a key element in Jak/RUSH signaling". Molecular and Cellular Endocrinology 325 (1–2): 143–9. PMC 2902710. PMID 20562009. doi:10.1016/j.mce.2010.05.010. 

Véxase tamén[editar | editar a fonte]

Bibliografía[editar | editar a fonte]

  • Berger R (May 2006). "[A recurrent mutation of the JAK2 gene in chronic myeloproliferative disorders]". Pathologie-Biologie 54 (4): 182–4. PMID 16084028. doi:10.1016/j.patbio.2005.07.002. 
  • Pargade V, Darnige L, Gaussem P (2006). "[Acquired mutation of JAK2 tyrosine kinase and polycythaemia vera]". Annales de Biologie Clinique 64 (1): 3–9. PMID 16420986. 
  • Staerk J, Kallin A, Royer Y, Diaconu CC, Dusa A, Demoulin JB, Vainchenker W, Constantinescu SN (March 2007). "JAK2, the JAK2 V617F mutant and cytokine receptors". Pathologie-Biologie 55 (2): 88–91. PMID 16904848. doi:10.1016/j.patbio.2006.06.003. 
  • Hsu HC (March 2007). "Pathogenetic role of JAK2 V617F mutation in chronic myeloproliferative disorders". Journal of the Chinese Medical Association 70 (3): 89–93. PMID 17389152. doi:10.1016/S1726-4901(09)70337-5. 

Ligazóns externas[editar | editar a fonte]