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. Kralovics R, Passamonti F, Buser A, Teo S, Tiedt R, Passweg J, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005;352:1779-90 pubmed
    ..Microsatellite mapping identified a 9pLOH region that included the Janus kinase 2 (JAK2) gene...
  2. Bogani C, Guglielmelli P, Antonioli E, Pancrazzi A, Bosi A, Vannucchi A. B-, T-, and NK-cell lineage involvement in JAK2V617F-positive patients with idiopathic myelofibrosis. Haematologica. 2007;92:258-9 pubmed
    An acquired JAK2 (V617F)mutation has been found in myeloid cells from most patients with chronic idiopathic myelofibrosis (IM), but whether it occurs in a common myelo-lymphoid, rather than a myeloid-restricted, progenitor cell is still ..
  3. 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...
  4. 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...
  5. 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...
  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

Publications112 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. 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...
  17. 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)...
  18. 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 ..
  19. 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...
  20. 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 ..
  21. 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...
  22. 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)...
  23. 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)...
  24. 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...
  25. 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 ..
  26. 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...
  27. 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...
  28. 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...
  29. 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 ..
  30. 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...
  31. 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 ..
  32. 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)...
  33. 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. ..
  34. 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. ..
  35. 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...
  36. 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...
  37. 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)...
  38. 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 ..
  39. 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...
  40. Wolanskyj A, Lasho T, Schwager S, McClure R, Wadleigh M, Lee S, et al. JAK2 mutation in essential thrombocythaemia: clinical associations and long-term prognostic relevance. Br J Haematol. 2005;131:208-13 pubmed
    Clinical correlates and long-term prognostic relevance of the JAK2(V617F) mutation was studied in 150 patients with essential thrombocythaemia (ET) from a single institution and followed for a median of 11.4 years...
  41. Lippert E, Boissinot M, Kralovics R, Girodon F, Dobo I, Praloran V, et al. The JAK2-V617F mutation is frequently present at diagnosis in patients with essential thrombocythemia and polycythemia vera. Blood. 2006;108:1865-7 pubmed
    We determined the allelic frequency of the JAK2-V617F mutation in DNA and assessed the expression levels of the mutant and wild-type JAK2 mRNA in granulocytes from 60 patients with essential thrombocythemia (ET) and 62 patients with ..
  42. Mercher T, Wernig G, Moore S, Levine R, Gu T, Fröhling S, et al. JAK2T875N is a novel activating mutation that results in myeloproliferative disease with features of megakaryoblastic leukemia in a murine bone marrow transplantation model. Blood. 2006;108:2770-9 pubmed
    ..These findings provide new insights into pathways and therapeutic targets that contribute to the pathogenesis of AMKL. ..
  43. Alchalby H, Badbaran A, Zabelina T, Kobbe G, Hahn J, Wolff D, et al. Impact of JAK2V617F mutation status, allele burden, and clearance after allogeneic stem cell transplantation for myelofibrosis. Blood. 2010;116:3572-81 pubmed publisher
    ..patients with known JAK2V617F mutation status who received ASCT after reduced-intensity conditioning, the impact of JAK2 genotype, JAK2V617F allele burden, and clearance of mutation after ASCT was evaluated...
  44. Nielsen C, Birgens H, Nordestgaard B, Kjaer L, Bojesen S. The JAK2 V617F somatic mutation, mortality and cancer risk in the general population. Haematologica. 2011;96:450-3 pubmed publisher
    b>JAK2 V617F is present in the majority of patients with myeloproliferative cancer; however, its prevalence and clinical significance in the general population is unknown...
  45. Lucet I, Fantino E, Styles M, Bamert R, Patel O, Broughton S, et al. The structural basis of Janus kinase 2 inhibition by a potent and specific pan-Janus kinase inhibitor. Blood. 2006;107:176-83 pubmed
    b>JAK2, a member of the Janus kinase (JAK) family of protein tyrosine kinases (PTKs), is an important intracellular mediator of cytokine signaling...
  46. Lu X, Huang L, Lodish H. Dimerization by a cytokine receptor is necessary for constitutive activation of JAK2V617F. J Biol Chem. 2008;283:5258-66 pubmed
    The majority of the BCR-ABL-negative myeloproliferative disorders express the mutant JAK2, JAK2V617F...
  47. Li S, Kralovics R, De Libero G, Theocharides A, Gisslinger H, Skoda R. Clonal heterogeneity in polycythemia vera patients with JAK2 exon12 and JAK2-V617F mutations. Blood. 2008;111:3863-6 pubmed publisher
    We studied the lineage distribution of JAK2 mutations in peripheral blood of 8 polycythemia vera (PV) patients with exon 12 mutations and in 21 PV patients with JAK2-V617F...
  48. Dusa A, Staerk J, Elliott J, Pecquet C, Poirel H, Johnston J, et al. Substitution of pseudokinase domain residue Val-617 by large non-polar amino acids causes activation of JAK2. J Biol Chem. 2008;283:12941-8 pubmed publisher
    Explaining the uniqueness of the acquired somatic JAK2 V617F mutation, which is present in more than 95% of polycythemia vera patients, has been a challenge...
  49. Za T, Fiorini A, Rossi E, Ciminello A, Chiusolo P, Leone G, et al. Prevalence of the JAK2 V617F mutation in patients with unprovoked venous thromboembolism of common sites and without overt myeloproliferative neoplasms. Br J Haematol. 2009;144:965-7 pubmed publisher
  50. Schnittger S, Bacher U, Haferlach C, Geer T, Muller P, Mittermuller J, et al. Detection of JAK2 exon 12 mutations in 15 patients with JAK2V617F negative polycythemia vera. Haematologica. 2009;94:414-8 pubmed publisher
    To further characterize JAK2 exon 12 mutations, we performed molecular screening in 409 patients with polycythemia vera or unclear erythrocytosis with unmutated JAK2V617. The frequency of JAK2exon12 mutations was 10/63 (15...
  51. Carbuccia N, Trouplin V, Gelsi Boyer V, Murati A, Rocquain J, Adelaide J, et al. Mutual exclusion of ASXL1 and NPM1 mutations in a series of acute myeloid leukemias. Leukemia. 2010;24:469-73 pubmed publisher
  52. Gual P, Baron V, Lequoy V, Van Obberghen E. Interaction of Janus kinases JAK-1 and JAK-2 with the insulin receptor and the insulin-like growth factor-1 receptor. Endocrinology. 1998;139:884-93 pubmed
  53. Vannucchi A, Antonioli E, Guglielmelli P, Rambaldi A, Barosi G, Marchioli R, et al. Clinical profile of homozygous JAK2 617V>F mutation in patients with polycythemia vera or essential thrombocythemia. Blood. 2007;110:840-6 pubmed
    b>JAK2 617V>F mutation occurs in a homozygous state in 25% to 30% of patients with polycythemia vera (PV) and 2% to 4% with essential thrombocythemia (ET)...
  54. Skoda R. Update on the impact of the JAK2 mutation on signalling pathways in myeloproliferative disorders. Eur J Haematol Suppl. 2007;:5-8 pubmed
  55. Basquiera A, Soria N, Ryser R, Salguero M, Moiraghi B, Sackmann F, et al. Clinical significance of V617F mutation of the JAK2 gene in patients with chronic myeloproliferative disorders. Hematology. 2009;14:323-30 pubmed publisher
    To determine the prevalence of JAK2 V617F mutation and its clinical correlation in patients with chronic myeloproliferative disorders (CMD): polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF)...
  56. Martinaud C, Brisou P, Mozziconacci M. Is the JAK2(V617F) mutation detectable in healthy volunteers?. Am J Hematol. 2010;85:287-8 pubmed publisher
  57. De Stefano V, Za T, Rossi E, Vannucchi A, Ruggeri M, Elli E, et al. Increased risk of recurrent thrombosis in patients with essential thrombocythemia carrying the homozygous JAK2 V617F mutation. Ann Hematol. 2010;89:141-6 pubmed publisher
    Evidence suggests that the JAK2 V617F mutation is associated with an increased risk of first thrombosis in patients with essential thrombocythemia (ET)...
  58. Xiong H, Chen Z, Liang Q, Du W, Chen H, Su W, et al. Inhibition of DNA methyltransferase induces G2 cell cycle arrest and apoptosis in human colorectal cancer cells via inhibition of JAK2/STAT3/STAT5 signalling. J Cell Mol Med. 2009;13:3668-79 pubmed publisher
    ..SHP1 expression correlates with down-regulation of Janus kinase/signal transducers and activators of transcription (JAK2/STAT3/STAT5) signalling, which is mediated in part by tyrosine dephosphorylation events and modulation of the ..
  59. Pardanani A, Lasho T, Schwager S, Finke C, Hussein K, Pruthi R, et al. JAK2V617F prevalence and allele burden in non-splanchnic venous thrombosis in the absence of overt myeloproliferative disorder. Leukemia. 2007;21:1828-9 pubmed
  60. Palandri F, Ottaviani E, Salmi F, Catani L, Polverelli N, Fiacchini M, et al. JAK2 V617F mutation in essential thrombocythemia: correlation with clinical characteristics, response to therapy and long-term outcome in a cohort of 275 patients. Leuk Lymphoma. 2009;50:247-53 pubmed publisher
    The JAK2(V617F) mutation occurs in 50% of patients with essential thrombocythemia (ET)...
  61. Anand S, Stedham F, Beer P, Gudgin E, Ortmann C, Bench A, et al. Effects of the JAK2 mutation on the hematopoietic stem and progenitor compartment in human myeloproliferative neoplasms. Blood. 2011;118:177-81 pubmed publisher
    The JAK2 V617F mutation is present in the majority of patients with a myeloproliferative neoplasm (MPN) and is sufficient to recapitulate an MPN in murine models...
  62. Witthuhn B, Quelle F, Silvennoinen O, Yi T, Tang B, Miura O, et al. JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin. Cell. 1993;74:227-36 pubmed
    ..Here we demonstrate that EPO induces tyrosine phosphorylation of JAK2 kinase and activates its in vitro autophosphorylation...
  63. Bercovich D, Ganmore I, Scott L, Wainreb G, Birger Y, Elimelech A, et al. Mutations of JAK2 in acute lymphoblastic leukaemias associated with Down's syndrome. Lancet. 2008;372:1484-92 pubmed publisher
    ..We tested the hypothesis that mutations in JAK2 might be a common molecular event in acute lymphoblastic leukaemia associated with Down's syndrome...
  64. Tefferi A, Strand J, Lasho T, Knudson R, Finke C, Gangat N, et al. Bone marrow JAK2V617F allele burden and clinical correlates in polycythemia vera. Leukemia. 2007;21:2074-5 pubmed
  65. Colomiere M, Ward A, Riley C, Trenerry M, Cameron Smith D, Findlay J, et al. Cross talk of signals between EGFR and IL-6R through JAK2/STAT3 mediate epithelial-mesenchymal transition in ovarian carcinomas. Br J Cancer. 2009;100:134-44 pubmed publisher
    ..This occurred concomitantly with activation of the downstream JAK2/STAT3 pathway...
  66. Jones A, Chase A, Silver R, Oscier D, Zoi K, Wang Y, et al. JAK2 haplotype is a major risk factor for the development of myeloproliferative neoplasms. Nat Genet. 2009;41:446-9 pubmed publisher
    ..vera, and roughly half of essential thrombocythemia and primary myelofibrosis acquire a unique somatic 1849G>T JAK2 mutation (encoding V617F) that is believed to be a critical driver of excess proliferation...
  67. Ungureanu D, Saharinen P, Junttila I, Hilton D, Silvennoinen O. Regulation of Jak2 through the ubiquitin-proteasome pathway involves phosphorylation of Jak2 on Y1007 and interaction with SOCS-1. Mol Cell Biol. 2002;22:3316-26 pubmed
    ..Ligand-induced receptor dimerization results in phosphorylation of Jak2 on activation loop tyrosine Y1007 and stimulation of its catalytic activity, which, in turn, results in activation ..
  68. Feener E, Rosario F, Dunn S, Stancheva Z, Myers M. Tyrosine phosphorylation of Jak2 in the JH2 domain inhibits cytokine signaling. Mol Cell Biol. 2004;24:4968-78 pubmed
    ..Although Jak2 and other Jak kinase family members are phosphorylated on numerous sites during cytokine signaling, the identity ..
  69. Trifa A, Cucuianu A, Petrov L, Urian L, Militaru M, Dima D, et al. The G allele of the JAK2 rs10974944 SNP, part of JAK2 46/1 haplotype, is strongly associated with JAK2 V617F-positive myeloproliferative neoplasms. Ann Hematol. 2010;89:979-83 pubmed publisher
    ..are myeloproliferative neoplasms, characterized in a majority of cases by a unique somatic point mutation, JAK2 V617F. Recently, it was shown that JAK2 V617F occurs more frequently on a specific JAK2 haplotype, named JAK2 46/1...
  70. Van Roosbroeck K, Cox L, Tousseyn T, Lahortiga I, Gielen O, Cauwelier B, et al. JAK2 rearrangements, including the novel SEC31A-JAK2 fusion, are recurrent in classical Hodgkin lymphoma. Blood. 2011;117:4056-64 pubmed publisher
    The genetics of classical Hodgkin lymphoma (cHL) is poorly understood. The finding of a JAK2-involving t(4;9)(q21;p24) in 1 case of cHL prompted us to characterize this translocation on a molecular level and to determine the prevalence of ..
  71. Argetsinger L, Kouadio J, Steen H, Stensballe A, Jensen O, Carter Su C. Autophosphorylation of JAK2 on tyrosines 221 and 570 regulates its activity. Mol Cell Biol. 2004;24:4955-67 pubmed
    The tyrosine kinase JAK2 is a key signaling protein for at least 20 receptors in the cytokine/hematopoietin receptor superfamily and is a component of signaling by insulin receptor and several G-protein-coupled receptors...
  72. Kim J, Cho Y, Choi S, Lee Y, Kim H, Jang S, et al. [JAK2 V617F and exon 12 genetic variations in Korean patients with BCR/ABL1-negative myeloproliferative neoplasms]. Korean J Lab Med. 2010;30:567-74 pubmed publisher
    b>JAK2 genetic variations have been described in a high proportion of patients with BCR/ABL1-negative myeloproliferative neoplasms (MPN)...
  73. Machado Neto J, Traina F, Lazarini M, Campos P, Pagnano K, Lorand Metze I, et al. Screening for hotspot mutations in PI3K, JAK2, FLT3 and NPM1 in patients with myelodysplastic syndromes. Clinics (Sao Paulo). 2011;66:793-9 pubmed
    ..the points most frequent for mutations (hotspot mutations) in phosphatidylinositol-3-kinase (PI3K), Janus kinase 2 (JAK2), FMS-like tyrosine kinase 3 (FLT3) and nucleophosmin (NPM1), which are involved in leukemia and other cancers, in ..
  74. Iwanaga E, Nanri T, Matsuno N, Kawakita T, Mitsuya H, Asou N. A JAK2-V617F activating mutation in addition to KIT and FLT3 mutations is associated with clinical outcome in patients with t(8;21)(q22;q22) acute myeloid leukemia. Haematologica. 2009;94:433-5 pubmed publisher
  75. Delhommeau F, Dupont S, Della Valle V, James C, Trannoy S, Massé A, et al. Mutation in TET2 in myeloid cancers. N Engl J Med. 2009;360:2289-301 pubmed publisher
    ..a dominant clone in hematopoietic progenitor cells that was positive for the V617F mutation in the Janus kinase 2 (JAK2) gene...
  76. Wernig G, Gonneville J, Crowley B, Rodrigues M, Reddy M, Hudon H, et al. The Jak2V617F oncogene associated with myeloproliferative diseases requires a functional FERM domain for transformation and for expression of the Myc and Pim proto-oncogenes. Blood. 2008;111:3751-9 pubmed publisher
    The V617F activating point mutation in Jak2 is associated with a proportion of myeloproliferative disorders...
  77. Boyd E, Bench A, Goday Fernandez A, Anand S, Vaghela K, Beer P, et al. Clinical utility of routine MPL exon 10 analysis in the diagnosis of essential thrombocythaemia and primary myelofibrosis. Br J Haematol. 2010;149:250-7 pubmed publisher
    Approximately 50% of essential thrombocythaemia and primary myelo-fibrosis patients do not have a JAK2 V617F mutation...
  78. Samanta A, Perazzona B, Chakraborty S, Sun X, Modi H, Bhatia R, et al. Janus kinase 2 regulates Bcr-Abl signaling in chronic myeloid leukemia. Leukemia. 2011;25:463-72 pubmed publisher
    ..Our findings indicate that inhibition of Janus kinase 2 (Jak2) in Bcr-Abl+ cells overcomes IM resistance although the precise mechanism of Jak2 action is unknown...
  79. Giorgetti Peraldi S, Peyrade F, Baron V, Van Obberghen E. Involvement of Janus kinases in the insulin signaling pathway. Eur J Biochem. 1995;234:656-60 pubmed
    ..Further, we found that both JAK1 and JAK2 constitutively associate with Grb2, through interaction with the SH3 domains of Grb2...
  80. Pezet A, Favre H, Kelly P, Edery M. Inhibition and restoration of prolactin signal transduction by suppressors of cytokine signaling. J Biol Chem. 1999;274:24497-502 pubmed
    Prolactin (PRL) has been shown to activate the cytoplasmic tyrosine kinase Janus kinase 2 (Jak2) and the subsequent recruitment of various signaling molecules including members of the signal transducer and activator of transcription ..
  81. Nakatake M, Monte Mór B, Debili N, Casadevall N, Ribrag V, Solary E, et al. JAK2(V617F) negatively regulates p53 stabilization by enhancing MDM2 via La expression in myeloproliferative neoplasms. Oncogene. 2012;31:1323-33 pubmed publisher
    b>JAK2(V617F) is a gain of function mutation that promotes cytokine-independent growth of myeloid cells and accounts for a majority of myeloproliferative neoplasms (MPN)...
  82. Ingram W, Lea N, Cervera J, Germing U, Fenaux P, Cassinat B, et al. The JAK2 V617F mutation identifies a subgroup of MDS patients with isolated deletion 5q and a proliferative bone marrow. Leukemia. 2006;20:1319-21 pubmed
  83. Walz C, Crowley B, Hudon H, Gramlich J, Neuberg D, Podar K, et al. Activated Jak2 with the V617F point mutation promotes G1/S phase transition. J Biol Chem. 2006;281:18177-83 pubmed
    ..The V617F activating point mutation in Jak2 has recently been associated with myeloproliferative disorders...
  84. Patel R, Lea N, Heneghan M, Westwood N, Milojkovic D, Thanigaikumar M, et al. Prevalence of the activating JAK2 tyrosine kinase mutation V617F in the Budd-Chiari syndrome. Gastroenterology. 2006;130:2031-8 pubmed
    ..A clonal mutation in JAK2 tyrosine kinase (JAK2V617F) occurs in a high proportion of patients with MPD and is of use in the characterization ..
  85. Smalberg J, Koehler E, Darwish Murad S, Plessier A, Seijo S, Trebicka J, et al. The JAK2 46/1 haplotype in Budd-Chiari syndrome and portal vein thrombosis. Blood. 2011;117:3968-73 pubmed publisher
    The germline JAK2 46/1 haplotype has been associated with the development of JAK2(V617F)-positive as well as JAK2(V617F)-negative myeloproliferative neoplasms (MPNs)...
  86. Tefferi A, Lasho T, Schwager S, Strand J, Elliott M, Mesa R, et al. The clinical phenotype of wild-type, heterozygous, and homozygous JAK2V617F in polycythemia vera. Cancer. 2006;106:631-5 pubmed
    Several studies have recently reported on the occurrence of a JAK2(V617F) mutation in myeloid cells from the majority of patients with polycythemia vera (PV). The clinical relevance of this novel observation currently is under study...
  87. Olcaydu D, Skoda R, Looser R, Li S, Cazzola M, Pietra D, et al. The 'GGCC' haplotype of JAK2 confers susceptibility to JAK2 exon 12 mutation-positive polycythemia vera. Leukemia. 2009;23:1924-6 pubmed publisher
  88. Carbuccia N, Murati A, Trouplin V, Brecqueville M, Adelaide J, Rey J, et al. Mutations of ASXL1 gene in myeloproliferative neoplasms. Leukemia. 2009;23:2183-6 pubmed publisher