Jak2

Summary

Gene Symbol: Jak2
Description: Janus kinase 2
Alias: JTK10, THCYT3, tyrosine-protein kinase JAK2, JAK-2, Janus kinase 2 (a protein tyrosine kinase)
Species: human
Products:     Jak2

Top Publications

  1. Levine R, Wadleigh M, Cools J, Ebert B, Wernig G, Huntly B, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005;7:387-97 pubmed
    ..In vitro analysis demonstrated that JAK2V617F is a constitutively active tyrosine kinase. ..
  2. Jamieson C, Gotlib J, Durocher J, Chao M, Mariappan M, Lay M, et al. The JAK2 V617F mutation occurs in hematopoietic stem cells in polycythemia vera and predisposes toward erythroid differentiation. Proc Natl Acad Sci U S A. 2006;103:6224-9 pubmed
    ..of patients with polycythemia vera (PV) harbor a valine-to-phenylalanine mutation at amino acid 617 (V617F) in the JAK2 signaling molecule, the stage of hematopoiesis at which the mutation arises is unknown...
  3. Mullighan C, Zhang J, Harvey R, Collins Underwood J, Schulman B, Phillips L, et al. JAK mutations in high-risk childhood acute lymphoblastic leukemia. Proc Natl Acad Sci U S A. 2009;106:9414-8 pubmed publisher
    ..Here, we report activating mutations in the Janus kinases JAK1 (n = 3), JAK2 (n = 16), and JAK3 (n = 1) in 20 (10.7%) of 187 BCR-ABL1-negative, high-risk pediatric ALL cases...
  4. Dawson M, Bannister A, Göttgens B, Foster S, Bartke T, Green A, et al. JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin. Nature. 2009;461:819-22 pubmed publisher
    Activation of Janus kinase 2 (JAK2) by chromosomal translocations or point mutations is a frequent event in haematological malignancies...
  5. Ma W, Kantarjian H, Zhang X, Yeh C, Zhang Z, Verstovsek S, et al. Mutation profile of JAK2 transcripts in patients with chronic myeloproliferative neoplasias. J Mol Diagn. 2009;11:49-53 pubmed publisher
    Here, we describe the JAK2 mutation profile in a series of approximately 20,000 blood samples from patients with clinically suspected myeloproliferative neoplasias...
  6. Jones A, Campbell P, Beer P, Schnittger S, Vannucchi A, Zoi K, et al. The JAK2 46/1 haplotype predisposes to MPL-mutated myeloproliferative neoplasms. Blood. 2010;115:4517-23 pubmed publisher
    The 46/1 JAK2 haplotype predisposes to V617F-positive myeloproliferative neoplasms, but the underlying mechanism is obscure...
  7. Beer P, Delhommeau F, LeCouedic J, Dawson M, Chen E, Bareford D, et al. Two routes to leukemic transformation after a JAK2 mutation-positive myeloproliferative neoplasm. Blood. 2010;115:2891-900 pubmed publisher
    Acute myeloid leukemia (AML) may follow a JAK2-positive myeloproliferative neoplasm (MPN), although the mechanisms of disease evolution, often involving loss of mutant JAK2, remain obscure...
  8. Prager M, Büttner J, Haas V, Baumgart D, Sturm A, Zeitz M, et al. The JAK2 variant rs10758669 in Crohn's disease: altering the intestinal barrier as one mechanism of action. Int J Colorectal Dis. 2012;27:565-73 pubmed publisher
    ..We analysed five variants (rs10758669 within JAK2, rs744166 within STAT3, rs4958847, rs11747270 and rs13361189 within IRGM) in adult German inflammatory bowel ..
  9. Quintas Cardama A, Verstovsek S. Molecular pathways: Jak/STAT pathway: mutations, inhibitors, and resistance. Clin Cancer Res. 2013;19:1933-40 pubmed publisher
    ..a large proportion of patients with myeloproliferative neoplasms (MPN) carry the acquired gain-of-function JAK2 V617F somatic mutation...

More Information

Publications163 found, 100 shown here

  1. Brooks A, Dai W, O Mara M, Abankwa D, Chhabra Y, Pelekanos R, et al. Mechanism of activation of protein kinase JAK2 by the growth hormone receptor. Science. 2014;344:1249783 pubmed publisher
    ..We present a complete mechanistic model for activation of receptor-bound JAK2, based on an archetypal cytokine receptor, the growth hormone receptor...
  2. Gäbler K, Rolvering C, Kaczor J, Eulenfeld R, Méndez S, Berchem G, et al. Cooperative effects of Janus and Aurora kinase inhibition by CEP701 in cells expressing Jak2V617F. J Cell Mol Med. 2013;17:265-76 pubmed publisher
    ..and the subsequent characterization of additional activities demonstrated for the first time that the most potent Jak2 inhibitor in our study, CEP701, also targets Aurora kinases...
  3. Shan Y, Gnanasambandan K, Ungureanu D, Kim E, Hammaren H, Yamashita K, et al. Molecular basis for pseudokinase-dependent autoinhibition of JAK2 tyrosine kinase. Nat Struct Mol Biol. 2014;21:579-84 pubmed publisher
    Janus kinase-2 (JAK2) mediates signaling by various cytokines, including erythropoietin and growth hormone. JAK2 possesses tandem pseudokinase and tyrosine-kinase domains...
  4. Brecqueville M, Rey J, Bertucci F, Coppin E, Finetti P, Carbuccia N, et al. Mutation analysis of ASXL1, CBL, DNMT3A, IDH1, IDH2, JAK2, MPL, NF1, SF3B1, SUZ12, and TET2 in myeloproliferative neoplasms. Genes Chromosomes Cancer. 2012;51:743-55 pubmed publisher
    ..We searched for mutations in ASXL1, CBL, DNMT3A, IDH1, IDH2, JAK2, MPL, NF1, SF3B1, SUZ12, and TET2 genes in 149 non-CML MPNs, including 127 "classic" MPNs cases...
  5. Bandaranayake R, Ungureanu D, Shan Y, Shaw D, Silvennoinen O, Hubbard S. Crystal structures of the JAK2 pseudokinase domain and the pathogenic mutant V617F. Nat Struct Mol Biol. 2012;19:754-9 pubmed publisher
    The protein tyrosine kinase JAK2 mediates signaling through numerous cytokine receptors. JAK2 possesses a pseudokinase domain (JH2) and a tyrosine kinase domain (JH1)...
  6. Lupardus P, Ultsch M, Wallweber H, Bir Kohli P, Johnson A, Eigenbrot C. Structure of the pseudokinase-kinase domains from protein kinase TYK2 reveals a mechanism for Janus kinase (JAK) autoinhibition. Proc Natl Acad Sci U S A. 2014;111:8025-30 pubmed publisher
    ..interface that are analogous to those in cancer-associated JAK alleles, including the V617F and "exon 12" JAK2 mutations, results in increased kinase activity in vitro...
  7. Nielsen C, Birgens H, Nordestgaard B, Bojesen S. Diagnostic value of JAK2 V617F somatic mutation for myeloproliferative cancer in 49 488 individuals from the general population. Br J Haematol. 2013;160:70-9 pubmed publisher
    The JAK2 V617F somatic mutation is present in the majority of patients with myeloproliferative cancer (polycythaemia vera, essential thrombocytosis, and primary myelofibrosis)...
  8. Rumi E, Pietra D, Ferretti V, Klampfl T, Harutyunyan A, Milosevic J, et al. JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes. Blood. 2014;123:1544-51 pubmed publisher
    Patients with essential thrombocythemia may carry JAK2 (V617F), an MPL substitution, or a calreticulin gene (CALR) mutation...
  9. Lange T, Edelmann A, Siebolts U, Krahl R, Nehring C, Jäkel N, et al. JAK2 p.V617F allele burden in myeloproliferative neoplasms one month after allogeneic stem cell transplantation significantly predicts outcome and risk of relapse. Haematologica. 2013;98:722-8 pubmed publisher
    ..Seventy simultaneously collected pairs of trephine and blood samples were quantified for JAK2 p.V617F allele burden to compare test sensitivity. The course of 30 patients with JAK2 p...
  10. Babon J, Kershaw N, Murphy J, Varghese L, Laktyushin A, Young S, et al. Suppression of cytokine signaling by SOCS3: characterization of the mode of inhibition and the basis of its specificity. Immunity. 2012;36:239-50 pubmed publisher
    ..We found that SOCS3 bound and directly inhibited the catalytic domains of JAK1, JAK2, and TYK2 but not JAK3 via an evolutionarily conserved motif unique to JAKs...
  11. Varghese L, Ungureanu D, Liau N, Young S, Laktyushin A, Hammaren H, et al. Mechanistic insights into activation and SOCS3-mediated inhibition of myeloproliferative neoplasm-associated JAK2 mutants from biochemical and structural analyses. Biochem J. 2014;458:395-405 pubmed publisher
    b>JAK2 (Janus kinase 2) initiates the intracellular signalling cascade downstream of cell surface receptor activation by cognate haemopoietic cytokines, including erythropoietin and thrombopoietin...
  12. Zhong Y, Wu J, Ma R, Cao H, Wang Z, Ding J, et al. Association of Janus kinase 2 (JAK2) polymorphisms with acute leukemia susceptibility. Int J Lab Hematol. 2012;34:248-53 pubmed publisher
    ..One of the members of this family, JAK2, plays a very important role in metabolizing carcinogens and medications...
  13. Vainchenker W, Constantinescu S. JAK/STAT signaling in hematological malignancies. Oncogene. 2013;32:2601-13 pubmed publisher
    ..human myeloproliferative neoplasms were discovered to be associated with a unique acquired somatic mutation in JAK2 (JAK2 V617F), rare exon 12 JAK2 mutations, or thrombopoietin receptor mutations that constitutively activate wild-..
  14. Spasovski V, Tosic N, Nikcevic G, Stojiljkovic M, Zukic B, Radmilovic M, et al. The influence of novel transcriptional regulatory element in intron 14 on the expression of Janus kinase 2 gene in myeloproliferative neoplasms. J Appl Genet. 2013;54:21-6 pubmed publisher
    The expression of Janus kinase 2 (JAK2) gene is altered in myeloproliferative neoplasms (MPN) and the regulation of transcription could be a mechanism that modulates JAK2 gene expression...
  15. Jovanovic J, Ivey A, Vannucchi A, Lippert E, Oppliger Leibundgut E, Cassinat B, et al. Establishing optimal quantitative-polymerase chain reaction assays for routine diagnosis and tracking of minimal residual disease in JAK2-V617F-associated myeloproliferative neoplasms: a joint European LeukemiaNet/MPN&MPNr-EuroNet (COST action BM. Leukemia. 2013;27:2032-9 pubmed publisher
    Reliable detection of JAK2-V617F is critical for accurate diagnosis of myeloproliferative neoplasms (MPNs); in addition, sensitive mutation-specific assays can be applied to monitor disease response...
  16. Larsen T, Pallisgaard N, Møller M, Hasselbalch H. The JAK2 V617F allele burden in essential thrombocythemia, polycythemia vera and primary myelofibrosis--impact on disease phenotype. Eur J Haematol. 2007;79:508-15 pubmed
    The JAK2 V617F tyrosine kinase mutation is present in the great majority of patients with polycythemia vera (PV), and approximately half of the patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF)...
  17. Haan S, Wüller S, Kaczor J, Rolvering C, Nöcker T, Behrmann I, et al. SOCS-mediated downregulation of mutant Jak2 (V617F, T875N and K539L) counteracts cytokine-independent signaling. Oncogene. 2009;28:3069-80 pubmed publisher
    Recently, mutations in the gene of Janus kinase 2 (Jak2) were discovered in patients suffering from chronic myeloproliferative disorders (MPD) and leukemia...
  18. Kittur J, Knudson R, Lasho T, Finke C, Gangat N, Wolanskyj A, et al. Clinical correlates of JAK2V617F allele burden in essential thrombocythemia. Cancer. 2007;109:2279-84 pubmed
    ..JAK2V617F allele burden imparts additional phenotypic effects in ET. ..
  19. Kiladjian J, Cervantes F, Leebeek F, Marzac C, Cassinat B, Chevret S, et al. The impact of JAK2 and MPL mutations on diagnosis and prognosis of splanchnic vein thrombosis: a report on 241 cases. Blood. 2008;111:4922-9 pubmed publisher
    ..We assessed the diagnostic and prognostic value of JAK2 and MPL515 mutations in 241 SVT patients (104 BCS, 137 PVT)...
  20. Baxter E, Scott L, Campbell P, East C, Fourouclas N, Swanton S, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005;365:1054-61 pubmed
    ..We investigated the role of the cytoplasmic tyrosine kinase JAK2 in patients with a myeloproliferative disorder...
  21. Theocharides A, Boissinot M, Girodon F, Garand R, Teo S, Lippert E, et al. Leukemic blasts in transformed JAK2-V617F-positive myeloproliferative disorders are frequently negative for the JAK2-V617F mutation. Blood. 2007;110:375-9 pubmed
    To study the role of the JAK2-V617F mutation in leukemic transformation, we examined 27 patients with myeloproliferative disorders (MPDs) who transformed to acute myeloid leukemia (AML)...
  22. Vannucchi A, Antonioli E, Guglielmelli P, Pancrazzi A, Guerini V, Barosi G, et al. Characteristics and clinical correlates of MPL 515W>L/K mutation in essential thrombocythemia. Blood. 2008;112:844-7 pubmed publisher
    ..These data indicate that MPLW515L/K mutations do not define a distinct phenotype in ET, although some differences depended on the JAK2V617F mutational status of the counterpart. ..
  23. Olcaydu D, Harutyunyan A, Jäger R, Berg T, Gisslinger B, Pabinger I, et al. A common JAK2 haplotype confers susceptibility to myeloproliferative neoplasms. Nat Genet. 2009;41:450-4 pubmed publisher
    ..In a series of investigations of the JAK2 gene in myeloproliferative neoplasms, we uncovered a new property of haplotypes that can explain their disease ..
  24. Baxter E, Hochhaus A, Bolufer P, Reiter A, Fernandez J, Senent L, et al. The t(4;22)(q12;q11) in atypical chronic myeloid leukaemia fuses BCR to PDGFRA. Hum Mol Genet. 2002;11:1391-7 pubmed
    ..Our findings indicate that apparently simple cytogenetic variants of t(9;22) do not always mask a cryptic BCR-ABL fusion, even when found in association with clinical and haematological indications of CML. ..
  25. Ishii T, Bruno E, Hoffman R, Xu M. Involvement of various hematopoietic-cell lineages by the JAK2V617F mutation in polycythemia vera. Blood. 2006;108:3128-34 pubmed
    The JAK2(V617F) mutation has been shown to occur in the overwhelming majority of patients with polycythemia vera (PV)...
  26. Mesa R, Tefferi A, Lasho T, Loegering D, McClure R, Powell H, et al. Janus kinase 2 (V617F) mutation status, signal transducer and activator of transcription-3 phosphorylation and impaired neutrophil apoptosis in myelofibrosis with myeloid metaplasia. Leukemia. 2006;20:1800-8 pubmed
    An activating point mutation in Janus kinase 2 (JAK2 V617F) was recently identified in myelofibrosis with myeloid metaplasia (MMM)...
  27. Lee W, Liu F, Lin J, Huang S, Lin H, Liao W, et al. JAK pathway induction of c-Myc critical to IL-5 stimulation of cell proliferation and inhibition of apoptosis. J Cell Biochem. 2009;106:929-36 pubmed publisher
    ..we demonstrate that IL-5 induced c-Myc RNA and protein expressions, as well as activated Janus kinases (JAK1 and JAK2) and signal transducer and activator of transcription-5b (STAT5b)...
  28. Kilpivaara O, Mukherjee S, Schram A, Wadleigh M, Mullally A, Ebert B, et al. A germline JAK2 SNP is associated with predisposition to the development of JAK2(V617F)-positive myeloproliferative neoplasms. Nat Genet. 2009;41:455-9 pubmed publisher
    ..Given that the identical somatic activating mutation in the JAK2 tyrosine kinase gene (JAK2(V617F)) is observed in most individuals with polycythemia vera, essential ..
  29. Passamonti F, Elena C, Schnittger S, Skoda R, Green A, Girodon F, et al. Molecular and clinical features of the myeloproliferative neoplasm associated with JAK2 exon 12 mutations. Blood. 2011;117:2813-6 pubmed publisher
    Although approximately 95% of patients with polycythemia vera (PV) harbor the V617F mutation in JAK2 exon 14, several mutations in exon 12 have been described in the remaining patients...
  30. Quelle F, Thierfelder W, Witthuhn B, Tang B, Cohen S, Ihle J. Phosphorylation and activation of the DNA binding activity of purified Stat1 by the Janus protein-tyrosine kinases and the epidermal growth factor receptor. J Biol Chem. 1995;270:20775-80 pubmed
    ..Co-expression of Stat1 with Tyk2, Jak1, or Jak2 resulted in the specific tyrosine phosphorylation of Stat1 at Tyr701, the residue phosphorylated in mammalian cells ..
  31. Huang L, Constantinescu S, Lodish H. The N-terminal domain of Janus kinase 2 is required for Golgi processing and cell surface expression of erythropoietin receptor. Mol Cell. 2001;8:1327-38 pubmed
    We show that Janus kinase 2 (JAK2), and more specifically just its intact N-terminal domain, binds to the erythropoietin receptor (EpoR) in the endoplasmic reticulum and promotes its cell surface expression...
  32. Lee J, Kim Y, Soung Y, Han K, Kim S, Rhim H, et al. The JAK2 V617F mutation in de novo acute myelogenous leukemias. Oncogene. 2006;25:1434-6 pubmed
    A missense somatic mutation in JAK2 gene (JAK2 V617F) has recently been reported in chronic myeloproliferative disorders, including polycythemia vera, essential thrombocythemia and myelofibrosis with myeloid metaplasia, strongly ..
  33. Zhou J, Xie Y, Zhao Y, Wang S, Li Y. Human gastrin mRNA expression up-regulated by Helicobacter pylori CagA through MEK/ERK and JAK2-signaling pathways in gastric cancer cells. Gastric Cancer. 2011;14:322-31 pubmed publisher
    ..Next, after the MEK/ERK and JAK2-signaling pathway inhibitors, U0126 and AG490, were used to treat the two cell lines, or the ERK1 and JAK2 genes ..
  34. Lu X, Levine R, Tong W, Wernig G, Pikman Y, Zarnegar S, et al. Expression of a homodimeric type I cytokine receptor is required for JAK2V617F-mediated transformation. Proc Natl Acad Sci U S A. 2005;102:18962-7 pubmed
    A recurrent somatic activating mutation in the nonreceptor tyrosine kinase JAK2 (JAK2V617F) occurs in the majority of patients with the myeloproliferative disorders polycythemia vera, essential thrombocythemia, myelofibrosis with myeloid ..
  35. Campbell P, Baxter E, Beer P, Scott L, Bench A, Huntly B, et al. Mutation of JAK2 in the myeloproliferative disorders: timing, clonality studies, cytogenetic associations, and role in leukemic transformation. Blood. 2006;108:3548-55 pubmed
    The identification of an acquired mutation of JAK2 in patients with myeloproliferative disorders has raised questions about the relationship between mutation-positive and mutation-negative subtypes, timing of the JAK2 mutation, and ..
  36. Endo T, Masuhara M, Yokouchi M, Suzuki R, Sakamoto H, Mitsui K, et al. A new protein containing an SH2 domain that inhibits JAK kinases. Nature. 1997;387:921-4 pubmed
    ..have now isolated a new SH2-domain-containing protein, JAB, which is a JAK-binding protein that interacts with the Jak2 tyrosine-kinase JH1 domain. JAB is structurally related to CIS, a cytokine-inducible SH2 protein...
  37. Elliott J, Suessmuth Y, Scott L, Nahlik K, McMullin M, Constantinescu S, et al. SOCS3 tyrosine phosphorylation as a potential bio-marker for myeloproliferative neoplasms associated with mutant JAK2 kinases. Haematologica. 2009;94:576-80 pubmed publisher
    b>JAK2 V617F, identified in the majority of patients with myeloproliferative neoplasms, tyrosine phosphorylates SOCS3 and escapes its inhibition...
  38. Putters J, da Silva Almeida A, van Kerkhof P, van Rossum A, Gracanin A, Strous G. Jak2 is a negative regulator of ubiquitin-dependent endocytosis of the growth hormone receptor. PLoS ONE. 2011;6:e14676 pubmed publisher
    ..In this study we show in Hek293 cells that Jak2 binding to the growth hormone receptor prevents endocytosis in a non-catalytic manner...
  39. Lakshmanan I, Ponnusamy M, Das S, Chakraborty S, Haridas D, Mukhopadhyay P, et al. MUC16 induced rapid G2/M transition via interactions with JAK2 for increased proliferation and anti-apoptosis in breast cancer cells. Oncogene. 2012;31:805-17 pubmed publisher
    ..we found that MUC16 interacts with the ezrin/radixin/moesin domain-containing protein of Janus kinase (JAK2) as demonstrated by the reciprocal immunoprecipitation method...
  40. Vignais M, Sadowski H, Watling D, Rogers N, Gilman M. Platelet-derived growth factor induces phosphorylation of multiple JAK family kinases and STAT proteins. Mol Cell Biol. 1996;16:1759-69 pubmed
    ..Here, we show that all three of the ubiquitously expressed JAKs--JAK1, JAK2, and Tyk2--become phosphorylated on tyrosine in both mouse BALB/c 3T3 cells and human fibroblasts engineered to ..
  41. Theocharides A, Passweg J, Medinger M, Looser R, Li S, Hao Shen H, et al. The allele burden of JAK2 mutations remains stable over several years in patients with myeloproliferative disorders. Haematologica. 2008;93:1890-3 pubmed publisher
    In a retrospective single center study we determined the time course of the JAK2-V617F or JAK2 exon 12 allele burden in DNA from purified granulocytes from 48 patients with myeloproliferative disorders...
  42. Pardanani A, Lasho T, Finke C, Hanson C, Tefferi A. Prevalence and clinicopathologic correlates of JAK2 exon 12 mutations in JAK2V617F-negative polycythemia vera. Leukemia. 2007;21:1960-3 pubmed
    ..Of these, five cases ( approximately 80%) were found to harbor one of the two JAK2 exon 12 mutations (F537-K539delinsL or N542-E543del) in bone marrow (BM) and/or peripheral blood cells...
  43. Ugo V, Le Gal G, Lecucq L, Mottier D, Oger E. Prevalence of the JAK2 V617F mutation is low among unselected patients with a first episode of unprovoked venous thromboembolism. J Thromb Haemost. 2008;6:203-5 pubmed
  44. Guglielmelli P, Barosi G, Specchia G, Rambaldi A, Lo Coco F, Antonioli E, et al. Identification of patients with poorer survival in primary myelofibrosis based on the burden of JAK2V617F mutated allele. Blood. 2009;114:1477-83 pubmed publisher
    ..Furthermore, survival was significantly reduced in the lower quartile compared with upper quartiles and JAK2 wild-type patients...
  45. Pardanani A, Lasho T, Hussein K, Schwager S, Finke C, Pruthi R, et al. JAK2V617F mutation screening as part of the hypercoagulable work-up in the absence of splanchnic venous thrombosis or overt myeloproliferative neoplasm: assessment of value in a series of 664 consecutive patients. Mayo Clin Proc. 2008;83:457-9 pubmed publisher
    ..Our study also suggests that the natural history of a JAK2V617F-positive "occult" MPN might be different from that of a typical MPN. ..
  46. De Stefano V, Za T, Rossi E, Fiorini A, Ciminello A, Luzzi C, et al. Influence of the JAK2 V617F mutation and inherited thrombophilia on the thrombotic risk among patients with essential thrombocythemia. Haematologica. 2009;94:733-7 pubmed publisher
    It is uncertain whether the JAK2 V617F mutation increases the thrombotic risk in patients with essential thrombocythemia, and it is unknown whether inherited thrombophilia is an additive risk factor in mutated subjects...
  47. Scott L. The JAK2 exon 12 mutations: a comprehensive review. Am J Hematol. 2011;86:668-76 pubmed publisher
    A variety of acquired mutations targeting JAK2 exon 12 are present in those patients with the myeloproliferative neoplasm, polycythemia vera, that lack the more common JAK2V617F mutation...
  48. Ungureanu D, Wu J, Pekkala T, Niranjan Y, Young C, Jensen O, et al. The pseudokinase domain of JAK2 is a dual-specificity protein kinase that negatively regulates cytokine signaling. Nat Struct Mol Biol. 2011;18:971-6 pubmed publisher
    Human JAK2 tyrosine kinase mediates signaling through numerous cytokine receptors...
  49. Pardanani A, Lasho T, Finke C, Gangat N, Wolanskyj A, Hanson C, et al. The JAK2 46/1 haplotype confers susceptibility to essential thrombocythemia regardless of JAK2V617F mutational status-clinical correlates in a study of 226 consecutive patients. Leukemia. 2010;24:110-4 pubmed publisher
    The germline JAK2 haplotype 46/1, tagged by the 'C' allele of single-nucleotide polymorphism (SNP) rs12343867 (C/T), has been associated with JAK2V617F (VF)-positive myeloproliferative neoplasms...
  50. Mesa R, Powell H, Lasho T, Dewald G, McClure R, Tefferi A. JAK2(V617F) and leukemic transformation in myelofibrosis with myeloid metaplasia. Leuk Res. 2006;30:1457-60 pubmed
    ..patients with leukemic transformation (LT) from myelofibrosis with myeloid metaplasia (MMM) 72% carried the JAK2(V617F) mutation...
  51. Vannucchi A, Pancrazzi A, Bogani C, Antonioli E, Guglielmelli P. A quantitative assay for JAK2(V617F) mutation in myeloproliferative disorders by ARMS-PCR and capillary electrophoresis. Leukemia. 2006;20:1055-60 pubmed
    A point mutation in the Janus tyrosine kinase 2 (JAK2) gene has been described in patients with chronic myeloproliferative disorders (MPD), but the clinical significance of JAK2(V617F), which may be harbored in either the heterozygote or ..
  52. Pietra D, Li S, Brisci A, Passamonti F, Rumi E, Theocharides A, et al. Somatic mutations of JAK2 exon 12 in patients with JAK2 (V617F)-negative myeloproliferative disorders. Blood. 2008;111:1686-9 pubmed
    We searched for JAK2 exon 12 mutations in patients with JAK2 (V617F)-negative myeloproliferative disorders...
  53. Plo I, Nakatake M, Malivert L, de Villartay J, Giraudier S, Villeval J, et al. JAK2 stimulates homologous recombination and genetic instability: potential implication in the heterogeneity of myeloproliferative disorders. Blood. 2008;112:1402-12 pubmed publisher
    The JAK2(V617F) mutation is frequently observed in classical myeloproliferative disorders, and disease progression is associated with a biallelic acquisition of the mutation occurring by mitotic recombination...
  54. Smith C, Fan G. The saga of JAK2 mutations and translocations in hematologic disorders: pathogenesis, diagnostic and therapeutic prospects, and revised World Health Organization diagnostic criteria for myeloproliferative neoplasms. Hum Pathol. 2008;39:795-810 pubmed publisher
    b>JAK2 is a tyrosine kinase involved in cytokine signaling...
  55. Marty C, Lacout C, Martin A, Hasan S, Jacquot S, Birling M, et al. Myeloproliferative neoplasm induced by constitutive expression of JAK2V617F in knock-in mice. Blood. 2010;116:783-7 pubmed publisher
    The Jak2(V617F) mutation is found in most classical BCR/ABL-negative myeloproliferative neoplasms (MPNs)...
  56. Peeters P, Raynaud S, Cools J, Wlodarska I, Grosgeorge J, Philip P, et al. Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia. Blood. 1997;90:2535-40 pubmed
    ..in atypical chronic myelogenous leukemia in transformation involve the ETV6 gene at 12p13 and the JAK2 gene at 9p24...
  57. Gozgit J, Bebernitz G, Patil P, Ye M, Parmentier J, Wu J, et al. Effects of the JAK2 inhibitor, AZ960, on Pim/BAD/BCL-xL survival signaling in the human JAK2 V617F cell line SET-2. J Biol Chem. 2008;283:32334-43 pubmed publisher
    The Janus-associated kinase 2 (JAK2) V617F mutation is believed to play a critical role in the pathogenesis of polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis...
  58. Ding L, Xu Y, Zhang W, Deng Y, Si M, Du Y, et al. MiR-375 frequently downregulated in gastric cancer inhibits cell proliferation by targeting JAK2. Cell Res. 2010;20:784-93 pubmed publisher
    ..Forced expression of miR-375 in gastric cancer cells significantly reduced the protein level of Janus kinase 2 (JAK2) and repressed the activity of a luciferase reporter carrying the 3'-untranslated region of JAK2, which was ..
  59. Olcaydu D, Rumi E, Harutyunyan A, Passamonti F, Pietra D, Pascutto C, et al. The role of the JAK2 GGCC haplotype and the TET2 gene in familial myeloproliferative neoplasms. Haematologica. 2011;96:367-74 pubmed publisher
    ..a group of diverse chronic myeloid malignancies that share pathogenic features such as acquired mutations in the JAK2, TET2, CBL and MPL genes...
  60. Levine R, Belisle C, Wadleigh M, Zahrieh D, Lee S, Chagnon P, et al. X-inactivation-based clonality analysis and quantitative JAK2V617F assessment reveal a strong association between clonality and JAK2V617F in PV but not ET/MMM, and identifies a subset of JAK2V617F-negative ET and MMM patients with clonal hematopoiesi. Blood. 2006;107:4139-41 pubmed
    ..In addition, some ET and MMM patients with clonal granulopoiesis have somatic mutations other than JAK2V617F. ..
  61. Regina S, Herault O, d Alteroche L, Binet C, Gruel Y. JAK2 V617F is specifically associated with idiopathic splanchnic vein thrombosis. J Thromb Haemost. 2007;5:859-61 pubmed
  62. Morgan K, Gilliland D. A role for JAK2 mutations in myeloproliferative diseases. Annu Rev Med. 2008;59:213-22 pubmed
    ..The JAK2V617F mutation alters the JAK2 tyrosine kinase to confer constitutive activation and affect downstream signaling pathways...
  63. Pardanani A, Fridley B, Lasho T, Gilliland D, Tefferi A. Host genetic variation contributes to phenotypic diversity in myeloproliferative disorders. Blood. 2008;111:2785-9 pubmed
    ..receptors for erythropoietin (EPOR), thrombopoietin (MPL), and granulocyte colony-stimulating factor (GCSFR), and JAK2. We genotyped 32 linkage disequilibrium tag single nucleotide polymorphism (SNP) loci in 179 white patients: 84 had ..
  64. Rapado I, Albizua E, Ayala R, Hernandez J, Garcia Alonso L, Grande S, et al. Validity test study of JAK2 V617F and allele burden quantification in the diagnosis of myeloproliferative diseases. Ann Hematol. 2008;87:741-9 pubmed publisher
    Several sensitive methods for the detection of JAK2 V617F mutation have been published recently, most of them based on Real Time polymerase chain reaction (PCR). However, only some of them have performed studies of diagnostic validity...
  65. Pelletier S, Gingras S, Funakoshi Tago M, Howell S, Ihle J. Two domains of the erythropoietin receptor are sufficient for Jak2 binding/activation and function. Mol Cell Biol. 2006;26:8527-38 pubmed
    Biochemical and genetic studies have shown that Jak2 is an essential component of EpoR signal transduction which is required for normal erythropoiesis...
  66. Ohyashiki K, Aota Y, Akahane D, Gotoh A, Ohyashiki J. JAK2(V617F) mutational status as determined by semiquantitative sequence-specific primer-single molecule fluorescence detection assay is linked to clinical features in chronic myeloproliferative disorders. Leukemia. 2007;21:1097-9 pubmed
  67. Kouroupi E, Zoi K, Parquet N, Zoi C, Kiladjian J, Grigoraki V, et al. Mutations in exon 12 of JAK2 are mainly found in JAK2 V617F-negative polycythaemia vera patients. Br J Haematol. 2008;142:676-9 pubmed publisher
  68. Pardanani A, Lasho T, Finke C, Mai M, McClure R, Tefferi A. IDH1 and IDH2 mutation analysis in chronic- and blast-phase myeloproliferative neoplasms. Leukemia. 2010;24:1146-51 pubmed publisher
    ..The entire study cohort was also screened for JAK2 and MPL mutations and JAK2V617F was found in three IDH-mutated cases (two PMF and one PV)...
  69. Modesti A, Bertolozzi I, Gamberi T, Marchetta M, Lumachi C, Coppo M, et al. Hyperglycemia activates JAK2 signaling pathway in human failing myocytes via angiotensin II-mediated oxidative stress. Diabetes. 2005;54:394-401 pubmed
    ..In nonfailing myocytes, JAK2 phosphorylation was enhanced by Ang II only in the presence of high glucose (25 mmol/l) via Ang II type I (AT1) ..
  70. Delhommeau F, Dupont S, Tonetti C, Massé A, Godin I, Le Couedic J, et al. Evidence that the JAK2 G1849T (V617F) mutation occurs in a lymphomyeloid progenitor in polycythemia vera and idiopathic myelofibrosis. Blood. 2007;109:71-7 pubmed
    The JAK2 V617F mutation has recently been described as an essential oncogenic event associated with polycythemia vera (PV), idiopathic myelofibrosis (IMF), and essential thrombocythemia...
  71. Hellstrom Lindberg E. Significance of JAK2 and TET2 mutations in myelodysplastic syndromes. Blood Rev. 2010;24:83-90 pubmed publisher
    ..The identification of JAK2 and MPL mutations, and more recently TET2, CBL and ASXL-1 mutations in these disorders provide a basis for ..
  72. Ma W, Kantarjian H, Zhang X, Wang X, Zhang Z, Yeh C, et al. JAK2 exon 14 deletion in patients with chronic myeloproliferative neoplasms. PLoS ONE. 2010;5:e12165 pubmed publisher
    The JAK2 V617F mutation in exon 14 is the most common mutation in chronic myeloproliferative neoplasms (MPNs); deletion of the entire exon 14 is rarely detected...
  73. Feng J, Witthuhn B, Matsuda T, Kohlhuber F, Kerr I, Ihle J. Activation of Jak2 catalytic activity requires phosphorylation of Y1007 in the kinase activation loop. Mol Cell Biol. 1997;17:2497-501 pubmed
    ..Within the Jak2 kinase domain, there is a region that has considerable sequence homology to the regulatory region of the insulin ..
  74. Finazzi G, Rambaldi A, Guerini V, Carobbo A, Barbui T. Risk of thrombosis in patients with essential thrombocythemia and polycythemia vera according to JAK2 V617F mutation status. Haematologica. 2007;92:135-6 pubmed
    ..with essential thrombocythemia (ET) and 77 with polycythemia vera (PV) classified according to the presence of the JAK2 V617F mutation...
  75. Quentmeier H, Geffers R, Jost E, MacLeod R, Nagel S, Röhrs S, et al. SOCS2: inhibitor of JAK2V617F-mediated signal transduction. Leukemia. 2008;22:2169-75 pubmed publisher
    Janus kinase 2 (JAK2)V617F-activating mutations (JAK2mu) occur in myeloproliferative disorders (MPDs) and myelodysplastic syndromes (MDSs)...
  76. Passamonti F, Rumi E, Pietra D, Elena C, Boveri E, Arcaini L, et al. A prospective study of 338 patients with polycythemia vera: the impact of JAK2 (V617F) allele burden and leukocytosis on fibrotic or leukemic disease transformation and vascular complications. Leukemia. 2010;24:1574-9 pubmed publisher
    We studied the relationship between JAK2 (V617F) mutant allele burden and clinical phenotype, disease progression and survival in patients with polycythemia vera (PV)...
  77. Deshpande A, Reddy M, Schade G, Ray A, Chowdary T, Griffin J, et al. Kinase domain mutations confer resistance to novel inhibitors targeting JAK2V617F in myeloproliferative neoplasms. Leukemia. 2012;26:708-15 pubmed publisher
    ..Several small molecule drugs targeting JAK2 are currently in clinical development for treatment in these diseases...
  78. Verstovsek S, Manshouri T, Quintas Cardama A, Harris D, Cortes J, Giles F, et al. WP1066, a novel JAK2 inhibitor, suppresses proliferation and induces apoptosis in erythroid human cells carrying the JAK2 V617F mutation. Clin Cancer Res. 2008;14:788-96 pubmed publisher
    The discovery of an activating somatic mutation in codon 617 of the gene encoding the Janus kinase (JAK)-2 (JAK2 V617F) in patients with myeloproliferative disorders has opened new avenues for the development of targeted therapies for ..
  79. Kilpivaara O, Levine R. JAK2 and MPL mutations in myeloproliferative neoplasms: discovery and science. Leukemia. 2008;22:1813-7 pubmed publisher
    ..A new era in MPN biology began in 2005 with the discovery of a somatic point mutation in JAK2 tyrosine kinase (JAK2V617F), which was identified in a significant proportion of patients with PV, ET and PMF...
  80. Toyama K, Karasawa M, Yamane A, Irisawa H, Yokohama A, Saitoh T, et al. JAK2-V617F mutation analysis of granulocytes and platelets from patients with chronic myeloproliferative disorders: advantage of studying platelets. Br J Haematol. 2007;139:64-9 pubmed
    There have been conflicting reports over the JAK2-V617F mutation status of platelets in chronic myeloproliferative diseases (CMPDs). The aim of this study was to analyse JAK2-V617F status, not only in granulocytes but also in platelets...
  81. Will B, Siddiqi T, Jorda M, Shimamura T, Luptakova K, Staber P, et al. Apoptosis induced by JAK2 inhibition is mediated by Bim and enhanced by the BH3 mimetic ABT-737 in JAK2 mutant human erythroid cells. Blood. 2010;115:2901-9 pubmed publisher
    The activating mutation JAK2 V617F plays a central role in the pathogenesis of polycythemia vera, essential thrombocythemia, and primary myelofibrosis...
  82. Irino T, Uemura M, Yamane H, Umemura S, Utsumi T, Kakazu N, et al. JAK2 V617F-dependent upregulation of PU.1 expression in the peripheral blood of myeloproliferative neoplasm patients. PLoS ONE. 2011;6:e22148 pubmed publisher
    ..e. granulocytic, erythroid, megakaryocytic and mast cell). JAK2 mutations, such as the common V617F substitution and the less common exon 12 mutations, are frequently detected in ..
  83. Huang H, Lin Y, Chen C, Chang T. Simultaneous activation of JAK1 and JAK2 confers IL-3 independent growth on Ba/F3 pro-B cells. J Cell Biochem. 2005;96:361-75 pubmed
    JAK1 and JAK2 are tyrosine kinases involved in the regulation of cell proliferation, differentiation, and survival. These proteins may play a key role in mediating the effects of the cytokine IL-3 on hematopoietic cells...
  84. Hsu H. Pathogenetic role of JAK2 V617F mutation in chronic myeloproliferative disorders. J Chin Med Assoc. 2007;70:89-93 pubmed
    ..Recently, 4 groups reported almost simultaneously Janus kinase 2 (JAK2) V617F mutation in more than 80% of PV patients, 30% of patients with ET and in about 50% of patients with ..
  85. Barosi G, Bergamaschi G, Marchetti M, Vannucchi A, Guglielmelli P, Antonioli E, et al. JAK2 V617F mutational status predicts progression to large splenomegaly and leukemic transformation in primary myelofibrosis. Blood. 2007;110:4030-6 pubmed
    Few investigators have evaluated the usefulness of the JAK2 V617F mutation for explaining the phenotypic variations and for predicting the risk of major clinical events in primary myelofibrosis (PMF)...
  86. Tefferi A, Lasho T, Huang J, Finke C, Mesa R, Li C, et al. Low JAK2V617F allele burden in primary myelofibrosis, compared to either a higher allele burden or unmutated status, is associated with inferior overall and leukemia-free survival. Leukemia. 2008;22:756-61 pubmed publisher
    ..We conclude that low V617F allele burden in PMF might indicate the presence of an overriding V617F-negative clone that confers a more aggressive disease phenotype. ..
  87. Girodon F, Schaeffer C, Cleyrat C, Mounier M, Lafont I, Santos F, et al. Frequent reduction or absence of detection of the JAK2-mutated clone in JAK2V617F-positive patients within the first years of hydroxyurea therapy. Haematologica. 2008;93:1723-7 pubmed publisher
    ..33% JAK2V617F at diagnosis, p<0.01). Prospective studies are needed to determine the prognostic value of reduced JAK2V617F allele burden under cytoreductive therapy. ..
  88. Tefferi A, Lasho T, Patnaik M, Finke C, Hussein K, Hogan W, et al. JAK2 germline genetic variation affects disease susceptibility in primary myelofibrosis regardless of V617F mutational status: nullizygosity for the JAK2 46/1 haplotype is associated with inferior survival. Leukemia. 2010;24:105-9 pubmed publisher
    A common JAK2 germline haplotype (46/1) has been associated with JAK2V617F (VF)-positive myeloproliferative neoplasms. The rs12343867 SNP (C/T) tags this haplotype...
  89. Randi M, Ruzzon E, Tezza F, Scapin M, Duner E, Scandellari R, et al. JAK2V617F mutation is common in old patients with polycythemia vera and essential thrombocythemia. Aging Clin Exp Res. 2011;23:17-21 pubmed
    ..JAK2V617F mutation occurs in 90% of polycythemia vera (PV) and in 50% of essential thrombocythemia (ET) patients...
  90. Tiedt R, Hao Shen H, Sobas M, Looser R, Dirnhofer S, Schwaller J, et al. Ratio of mutant JAK2-V617F to wild-type Jak2 determines the MPD phenotypes in transgenic mice. Blood. 2008;111:3931-40 pubmed
    An acquired somatic mutation in the JAK2 gene (JAK2-V617F) is present in the majority of patients with myeloproliferative disorders (MPDs)...
  91. Sazawal S, Bajaj J, Chikkara S, Jain S, Bhargava R, Mahapatra M, et al. Prevalence of JAK2 V617F mutation in Indian patients with chronic myeloproliferative disorders. Indian J Med Res. 2010;132:423-7 pubmed
    The Janus-associated Kinase-2 mutation JAK2 V617F in chronic myeloproliferative disorders (CMPDs) has been described as a frequent genetic event in majority of patients with polycythemia vera (PV), essential thrombocythemia (ET) and ..
  92. Yasukawa H, Misawa H, Sakamoto H, Masuhara M, Sasaki A, Wakioka T, et al. The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop. EMBO J. 1999;18:1309-20 pubmed
    ..presented here we demonstrate that JAB specifically binds to the tyrosine residue (Y1007) in the activation loop of JAK2, whose phosphorylation is required for activation of kinase activity...