Jak2

Summary

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

Top Publications

  1. ncbi Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis
    Ross L Levine
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Cell 7:387-97. 2005
  2. ncbi Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders
    E Joanna Baxter
    Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
    Lancet 365:1054-61. 2005
  3. doi Mutation in TET2 in myeloid cancers
    Francois Delhommeau
    INSERM U790, Institut Gustave Roussy, Villejuif, France
    N Engl J Med 360:2289-301. 2009
  4. ncbi JAK2 V617F mutational status predicts progression to large splenomegaly and leukemic transformation in primary myelofibrosis
    Giovanni Barosi
    Unit of Clinical Epidemiology and Center for the Study of Myelofibrosis, Istituto di Ricovero e Cura a Carattere Scientifico IRCCS Policlinico S Matteo Foundation, Pavia, Italy
    Blood 110:4030-6. 2007
  5. pmc 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 BM0902)
    J V Jovanovic
    King s College London School of Medicine, Cancer Genetics Lab, Department of Medical and Molecular Genetics, London, UK
    Leukemia 27:2032-9. 2013
  6. doi 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
    A Tefferi
    Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
    Leukemia 22:756-61. 2008
  7. ncbi Ratio of mutant JAK2-V617F to wild-type Jak2 determines the MPD phenotypes in transgenic mice
    Ralph Tiedt
    Department of Research, Experimental Hematology, University Hospital Basel, Hebelstrasse 20, 4031 Basel, Switzerland
    Blood 111:3931-40. 2008
  8. pmc Cross talk of signals between EGFR and IL-6R through JAK2/STAT3 mediate epithelial-mesenchymal transition in ovarian carcinomas
    M Colomiere
    Women s Cancer Research Centre, Royal Women s Hospital, Melbourne, Australia
    Br J Cancer 100:134-44. 2009
  9. pmc JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes
    Elisa Rumi
    Department of Hematology Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy
    Blood 123:1544-51. 2014
  10. ncbi A quantitative assay for JAK2(V617F) mutation in myeloproliferative disorders by ARMS-PCR and capillary electrophoresis
    A M Vannucchi
    Department of Hematology, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy
    Leukemia 20:1055-60. 2006

Detail Information

Publications311 found, 100 shown here

  1. ncbi Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis
    Ross L Levine
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Cell 7:387-97. 2005
    ..In vitro analysis demonstrated that JAK2V617F is a constitutively active tyrosine kinase...
  2. ncbi Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders
    E Joanna Baxter
    Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
    Lancet 365:1054-61. 2005
    ..We investigated the role of the cytoplasmic tyrosine kinase JAK2 in patients with a myeloproliferative disorder.
  3. doi Mutation in TET2 in myeloid cancers
    Francois Delhommeau
    INSERM U790, Institut Gustave Roussy, Villejuif, France
    N Engl J Med 360:2289-301. 2009
    ..The myelodysplastic syndromes and myeloproliferative disorders are associated with deregulated production of myeloid cells. The mechanisms underlying these disorders are not well defined...
  4. ncbi JAK2 V617F mutational status predicts progression to large splenomegaly and leukemic transformation in primary myelofibrosis
    Giovanni Barosi
    Unit of Clinical Epidemiology and Center for the Study of Myelofibrosis, Istituto di Ricovero e Cura a Carattere Scientifico IRCCS Policlinico S Matteo Foundation, Pavia, Italy
    Blood 110:4030-6. 2007
    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)...
  5. pmc 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 BM0902)
    J V Jovanovic
    King s College London School of Medicine, Cancer Genetics Lab, Department of Medical and Molecular Genetics, London, UK
    Leukemia 27:2032-9. 2013
    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...
  6. doi 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
    A Tefferi
    Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
    Leukemia 22:756-61. 2008
    ..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...
  7. ncbi Ratio of mutant JAK2-V617F to wild-type Jak2 determines the MPD phenotypes in transgenic mice
    Ralph Tiedt
    Department of Research, Experimental Hematology, University Hospital Basel, Hebelstrasse 20, 4031 Basel, Switzerland
    Blood 111:3931-40. 2008
    An acquired somatic mutation in the JAK2 gene (JAK2-V617F) is present in the majority of patients with myeloproliferative disorders (MPDs)...
  8. pmc Cross talk of signals between EGFR and IL-6R through JAK2/STAT3 mediate epithelial-mesenchymal transition in ovarian carcinomas
    M Colomiere
    Women s Cancer Research Centre, Royal Women s Hospital, Melbourne, Australia
    Br J Cancer 100:134-44. 2009
    ..This occurred concomitantly with activation of the downstream JAK2/STAT3 pathway...
  9. pmc JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes
    Elisa Rumi
    Department of Hematology Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy
    Blood 123:1544-51. 2014
    Patients with essential thrombocythemia may carry JAK2 (V617F), an MPL substitution, or a calreticulin gene (CALR) mutation...
  10. ncbi A quantitative assay for JAK2(V617F) mutation in myeloproliferative disorders by ARMS-PCR and capillary electrophoresis
    A M Vannucchi
    Department of Hematology, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy
    Leukemia 20:1055-60. 2006
    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 ..
  11. doi JAK2(V617F) negatively regulates p53 stabilization by enhancing MDM2 via La expression in myeloproliferative neoplasms
    M Nakatake
    INSERM UMR 1009, Villejuif, France
    Oncogene 31:1323-33. 2012
    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)...
  12. pmc Jak2 is a negative regulator of ubiquitin-dependent endocytosis of the growth hormone receptor
    Joyce Putters
    Department of Cell Biology and Institute of Biomembranes, University Medical Center Utrecht, Utrecht, The Netherlands
    PLoS ONE 6:e14676. 2011
    ..Degradation of certain cytokine receptors is mediated by the ubiquitin ligase SCF(βTrCP). In several instances, Janus kinase (Jak) family members can stabilise their cognate cytokine receptors at the cell surface...
  13. doi Identification of patients with poorer survival in primary myelofibrosis based on the burden of JAK2V617F mutated allele
    Paola Guglielmelli
    Unita Funzionale di Ematologia, Dipartimento di Area Critica, Universita di Firenze, and Istituto Toscano Tumori, Firenze, Italy
    Blood 114:1477-83. 2009
    ..Furthermore, survival was significantly reduced in the lower quartile compared with upper quartiles and JAK2 wild-type patients...
  14. pmc Jak2 inhibition deactivates Lyn kinase through the SET-PP2A-SHP1 pathway, causing apoptosis in drug-resistant cells from chronic myelogenous leukemia patients
    A K Samanta
    Department of Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
    Oncogene 28:1669-81. 2009
    ..In Bcr-Abl+ cells inhibition of Jak2, a downstream target of Bcr-Abl, by either Jak2 inhibitors or Jak2-specific short interfering RNA (siRNA) reduced ..
  15. ncbi A new protein containing an SH2 domain that inhibits JAK kinases
    T A Endo
    Institute of Life Science, Kurume University, Aikawamachi, Japan
    Nature 387:921-4. 1997
    ..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...
  16. ncbi Clinical profile of homozygous JAK2 617V>F mutation in patients with polycythemia vera or essential thrombocythemia
    Alessandro M Vannucchi
    Department of Hematology, University of Florence, 50134 Florence, Italy
    Blood 110:840-6. 2007
    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)...
  17. doi IDH1 and IDH2 mutation analysis in chronic- and blast-phase myeloproliferative neoplasms
    A Pardanani
    Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA
    Leukemia 24:1146-51. 2010
    ..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. doi The impact of JAK2 and MPL mutations on diagnosis and prognosis of splanchnic vein thrombosis: a report on 241 cases
    Jean Jacques Kiladjian
    Assistance Publique Hopitaux de Paris, Hopital Avicenne, Service d Hematologie Clinique, and Université Paris 13, Bobigny, France
    Blood 111:4922-9. 2008
    ..We assessed the diagnostic and prognostic value of JAK2 and MPL515 mutations in 241 SVT patients (104 BCS, 137 PVT)...
  19. ncbi The N-terminal domain of Janus kinase 2 is required for Golgi processing and cell surface expression of erythropoietin receptor
    L J Huang
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Mol Cell 8:1327-38. 2001
    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...
  20. ncbi CIS3/SOCS-3 suppresses erythropoietin (EPO) signaling by binding the EPO receptor and JAK2
    A Sasaki
    Institute of Life Science, Kurume University, Aikawa machi 2432 3, Kurume 839 0861, Japan
    J Biol Chem 275:29338-47. 2000
    ..CIS3 binds directly to the EPOR as well as JAK2 and inhibits EPO-dependent proliferation and STAT5 activation...
  21. ncbi The JAK2-V617F mutation is frequently present at diagnosis in patients with essential thrombocythemia and polycythemia vera
    Eric Lippert
    Laboratoire d Hématologie du CHU de Bourdeaux, France
    Blood 108:1865-7. 2006
    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 ..
  22. doi Genetic factors in chronic inflammation: single nucleotide polymorphisms in the STAT-JAK pathway, susceptibility to DNA damage and Crohn's disease in a New Zealand population
    Lynnette R Ferguson
    Discipline of Nutrition, FM and HS, The University of Auckland, Auckland, New Zealand Nutrigenomics New Zealand, New Zealand
    Mutat Res 690:108-15. 2010
    ..Two members of that pathway, STAT3 and JAK2, enhanced the risk of Crohn's disease (CD) in recent genome-wide association studies...
  23. ncbi Lyn physically associates with the erythropoietin receptor and may play a role in activation of the Stat5 pathway
    H Chin
    First Department of Internal Medicine and School of Allied Health Sciences, Tokyo Medical and Dental University, Tokyo, Japan
    Blood 91:3734-45. 1998
    ..We have previously shown that the Jak2 tyrosine kinase couples with the EpoR to transduce a growth signal...
  24. pmc Platelet-derived growth factor induces phosphorylation of multiple JAK family kinases and STAT proteins
    M L Vignais
    Cold Spring Harbor Laboratory, New York 11724, USA
    Mol Cell Biol 16:1759-69. 1996
    ..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 ..
  25. pmc Cooperative effects of Janus and Aurora kinase inhibition by CEP701 in cells expressing Jak2V617F
    Karoline Gäbler
    Life Sciences Research Unit Signal Transduction Laboratory, University of Luxembourg, Luxembourg, Luxembourg
    J Cell Mol Med 17:265-76. 2013
    ..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...
  26. doi JAK/STAT signaling in hematological malignancies
    W Vainchenker
    INSERM, UMR 1009, Hématopoïèse Normale et Pathologique, Villejuif, France
    Oncogene 32:2601-13. 2013
    ..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-..
  27. pmc Regulation of Jak2 through the ubiquitin-proteasome pathway involves phosphorylation of Jak2 on Y1007 and interaction with SOCS-1
    Daniela Ungureanu
    Institute of Medical Technology, University of Tampere, FIN 33014 Tampere, Finland
    Mol Cell Biol 22:3316-26. 2002
    ..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 ..
  28. pmc MUC16 induced rapid G2/M transition via interactions with JAK2 for increased proliferation and anti-apoptosis in breast cancer cells
    I Lakshmanan
    Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198 5870, USA
    Oncogene 31:805-17. 2012
    ..we found that MUC16 interacts with the ezrin/radixin/moesin domain-containing protein of Janus kinase (JAK2) as demonstrated by the reciprocal immunoprecipitation method...
  29. ncbi Risk of thrombosis in patients with essential thrombocythemia and polycythemia vera according to JAK2 V617F mutation status
    Guido Finazzi
    Haematologica 92:135-6. 2007
    ..with essential thrombocythemia (ET) and 77 with polycythemia vera (PV) classified according to the presence of the JAK2 V617F mutation...
  30. pmc Is the absence of JAK2 mutation a risk factor for bleeding in essential thrombocythemia? An analysis of 106 patients
    Andrea Patriarca
    Dipartimento di Ematologia, Servizio di Prevenzione e Cura Sindromi Emorragiche e Trombotiche, Ospedale Civile dello Spirito Santo, Pescara, Italy
    Blood Transfus 8:21-7. 2010
    b>JAK2(V617F) mutation has been recognized as a possible thrombotic risk factor in essential thrombocythaemia (ET). It's role is probably due to an increased myeloid proliferation and white blood cells (WBC) activation...
  31. ncbi The JAK2 V617F allele burden in essential thrombocythemia, polycythemia vera and primary myelofibrosis--impact on disease phenotype
    Thomas Stauffer Larsen
    Department of Haematology, Odense University Hospital, Odense C, Denmark
    Eur J Haematol 79:508-15. 2007
    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)...
  32. pmc JAK2 V617F-dependent upregulation of PU.1 expression in the peripheral blood of myeloproliferative neoplasm patients
    Tamotsu Irino
    Shiga Medical Center for Adults, Moriyama, Japan
    PLoS ONE 6:e22148. 2011
    ..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 ..
  33. ncbi 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
    P Peeters
    Center for Human Genetics, University of Leuven, Belgium
    Blood 90:2535-40. 1997
    ..in atypical chronic myelogenous leukemia in transformation involve the ETV6 gene at 12p13 and the JAK2 gene at 9p24...
  34. doi A BCR-JAK2 fusion gene as the result of a t(9;22)(p24;q11) in a patient with acute myeloid leukemia
    Gabriella Cirmena
    Department of Hematology, University of Genoa, V le Benedetto XV 6, 16132 Genoa, Italy
    Cancer Genet Cytogenet 183:105-8. 2008
    We report the occurrence of a BCR-JAK2 fusion gene in a case of acute myeloid leukemia (AML) resulting from a t(9;22)(p24;q11) translocation as the sole cytogenetic abnormality...
  35. pmc Apoptosis induced by JAK2 inhibition is mediated by Bim and enhanced by the BH3 mimetic ABT-737 in JAK2 mutant human erythroid cells
    Britta Will
    Division of Hematology Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    Blood 115:2901-9. 2010
    The activating mutation JAK2 V617F plays a central role in the pathogenesis of polycythemia vera, essential thrombocythemia, and primary myelofibrosis...
  36. pmc The pseudokinase domain of JAK2 is a dual-specificity protein kinase that negatively regulates cytokine signaling
    Daniela Ungureanu
    Institute of Biomedical Technology, University of Tampere, and Tampere University Hospital, Tampere, Finland
    Nat Struct Mol Biol 18:971-6. 2011
    Human JAK2 tyrosine kinase mediates signaling through numerous cytokine receptors...
  37. doi The G allele of the JAK2 rs10974944 SNP, part of JAK2 46/1 haplotype, is strongly associated with JAK2 V617F-positive myeloproliferative neoplasms
    Adrian P Trifa
    Department of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania
    Ann Hematol 89:979-83. 2010
    ..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...
  38. ncbi Involvement of Janus kinases in the insulin signaling pathway
    S Giorgetti-Peraldi
    Institut National de la Santé et de la Recherche Médicale INSERM U145, Faculte de Medecine, Nice, France
    Eur J Biochem 234:656-60. 1995
    ..Further, we found that both JAK1 and JAK2 constitutively associate with Grb2, through interaction with the SH3 domains of Grb2...
  39. doi 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
    A Tefferi
    Division of Hematology, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
    Leukemia 24:105-9. 2010
    A common JAK2 germline haplotype (46/1) has been associated with JAK2V617F (VF)-positive myeloproliferative neoplasms. The rs12343867 SNP (C/T) tags this haplotype...
  40. ncbi The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2
    Andreas Reiter
    III Medizinische Universitätsklinik, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, Mannheim, Germany
    Cancer Res 65:2662-7. 2005
    ..situ hybridization studies of one patient indicated that the nonreceptor tyrosine kinase Janus-activated kinase 2 (JAK2) at 9p24 was disrupted...
  41. doi JAK2V617F mutation for the early diagnosis of Ph- myeloproliferative neoplasms in patients with venous thromboembolism: a meta-analysis
    Francesco Dentali
    Department of Clinical Medicine, University of Insubria, Varese, Italy
    Blood 113:5617-23. 2009
    ..Therefore, we performed a systematic review to assess the frequency of JAK2 mutation in VTE patients and the role of JAK2V617F mutation in the diagnosis of myeloproliferative neoplasms...
  42. doi α4β2 nicotinic receptors partially mediate anti-inflammatory effects through Janus kinase 2-signal transducer and activator of transcription 3 but not calcium or cAMP signaling
    Vishnu Hosur
    Department of Pharmaceutical Science, Northeastern University, Boston, Massachusetts 02115, USA
    Mol Pharmacol 79:167-74. 2011
    ..the effects of nicotine on NF-κB activity were significantly blocked by the highly specific janus kinase 2 (JAK2) inhibitor α-cyano-(3,4-dihydroxy)-N-benzylcinnamide (AG-490) and the signal transducer and activator of ..
  43. pmc SOCS3 tyrosine phosphorylation as a potential bio-marker for myeloproliferative neoplasms associated with mutant JAK2 kinases
    Joanne Elliott
    Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, QUB, 2 Floor, Whitla Medical Building, 97 Lisburn Rd, Belfast BT97BL, Northern Ireland
    Haematologica 94:576-80. 2009
    b>JAK2 V617F, identified in the majority of patients with myeloproliferative neoplasms, tyrosine phosphorylates SOCS3 and escapes its inhibition...
  44. doi Effects of the JAK2 inhibitor, AZ960, on Pim/BAD/BCL-xL survival signaling in the human JAK2 V617F cell line SET-2
    Joseph M Gozgit
    Cancer Biosciences, AstraZeneca R and D Boston, Waltham, Massachusetts 02451, USA
    J Biol Chem 283:32334-43. 2008
    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...
  45. ncbi Prospective identification of high-risk polycythemia vera patients based on JAK2(V617F) allele burden
    A M Vannucchi
    Department of Hematology, University of Florence, Florence, Italy
    Leukemia 21:1952-9. 2007
    The aim of this study was to determine whether the burden of JAK2(V617F) allele correlated with major clinical outcomes in patients with polycythemia vera (PV)...
  46. ncbi Leukemic blasts in transformed JAK2-V617F-positive myeloproliferative disorders are frequently negative for the JAK2-V617F mutation
    Alexandre Theocharides
    Department of Research, Experimental Hematology, University Hospital Basel, Basel, Switzerland
    Blood 110:375-9. 2007
    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)...
  47. ncbi Relation between JAK2 (V617F) mutation status, granulocyte activation, and constitutive mobilization of CD34+ cells into peripheral blood in myeloproliferative disorders
    Francesco Passamonti
    Department of Hematology, IRCCS Policlinico San Matteo, 27100 Pavia, Italy
    Blood 107:3676-82. 2006
    We studied the relationship between granulocyte JAK2 (V617F) mutation status, circulating CD34(+) cells, and granulocyte activation in myeloproliferative disorders...
  48. ncbi Phosphorylation and activation of the DNA binding activity of purified Stat1 by the Janus protein-tyrosine kinases and the epidermal growth factor receptor
    F W Quelle
    Department of Biochemistry, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    J Biol Chem 270:20775-80. 1995
    ..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 ..
  49. doi Mutation analysis of ASXL1, CBL, DNMT3A, IDH1, IDH2, JAK2, MPL, NF1, SF3B1, SUZ12, and TET2 in myeloproliferative neoplasms
    Mandy Brecqueville
    Laboratoire d Oncologie Moleculaire, Centre de Recherche en Cancerologie de Marseille, UMR1068 Inserm, Institut Paoli Calmettes, Marseille, France
    Genes Chromosomes Cancer 51:743-55. 2012
    ..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...
  50. doi Myeloproliferative neoplasm induced by constitutive expression of JAK2V617F in knock-in mice
    Caroline Marty
    Inserm U1009, Institut Gustave Roussy, PR1, 114 rue Edouard Vaillant, 94805 Villejuif, France
    Blood 116:783-7. 2010
    The Jak2(V617F) mutation is found in most classical BCR/ABL-negative myeloproliferative neoplasms (MPNs)...
  51. pmc Two domains of the erythropoietin receptor are sufficient for Jak2 binding/activation and function
    Stephane Pelletier
    Department of Biochemistry, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Mol Cell Biol 26:8527-38. 2006
    Biochemical and genetic studies have shown that Jak2 is an essential component of EpoR signal transduction which is required for normal erythropoiesis...
  52. doi Influence of JAK2V617F allele burden on phenotype in essential thrombocythemia
    Elisabetta Antonioli
    Department of Hematology, University of Florence, 50134, Florence, Italy
    Haematologica 93:41-8. 2008
    Fifty to sixty percent of patients with essential thrombocythemia harbor the JAK2(V617F) mutation. The impact of this mutation on clinical phenotype is still debated...
  53. ncbi Bone marrow JAK2V617F allele burden and clinical correlates in polycythemia vera
    A Tefferi
    Leukemia 21:2074-5. 2007
  54. pmc Tyrosine phosphorylation of Jak2 in the JH2 domain inhibits cytokine signaling
    Edward P Feener
    Joslin Proteomics Core, Joslin Diabetes Center, 1 Joslin Pl, Boston, MA 02215, USA
    Mol Cell Biol 24:4968-78. 2004
    ..Although Jak2 and other Jak kinase family members are phosphorylated on numerous sites during cytokine signaling, the identity ..
  55. pmc The JAK2 V617F somatic mutation, mortality and cancer risk in the general population
    Camilla Nielsen
    Faculty of Health Sciences, University of Copenhagen, Denmark
    Haematologica 96:450-3. 2011
    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...
  56. doi SOCS2: inhibitor of JAK2V617F-mediated signal transduction
    H Quentmeier
    DSMZ German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany
    Leukemia 22:2169-75. 2008
    Janus kinase 2 (JAK2)V617F-activating mutations (JAK2mu) occur in myeloproliferative disorders (MPDs) and myelodysplastic syndromes (MDSs)...
  57. pmc Autophosphorylation of JAK2 on tyrosines 221 and 570 regulates its activity
    Lawrence S Argetsinger
    Department of Molecular and Integrative Physiology, The University of Michigan Medical School, Ann Arbor, MI 48109 0622, USA
    Mol Cell Biol 24:4955-67. 2004
    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...
  58. doi Validity test study of JAK2 V617F and allele burden quantification in the diagnosis of myeloproliferative diseases
    Inmaculada Rapado
    Hematology Service, Hospital Universitario 12 de Octubre, Avenida Córdoba s n, 28041 Madrid, Spain
    Ann Hematol 87:741-9. 2008
    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...
  59. doi The allele burden of JAK2 mutations remains stable over several years in patients with myeloproliferative disorders
    Alexandre Theocharides
    Experimental Hematology, Department of Biomedicine, University Hospital Basel, Basel, Switzerland
    Haematologica 93:1890-3. 2008
    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...
  60. doi Detection of low allele burden of JAK2 exon 12 mutations using TA-cloning in patients with erythrocytosis
    Junko H Ohyashiki
    Intractable Disease Therapeutic Research Center, Tokyo Medical University, 6 7 1 Nishishinjuku, Shinjuku ku, Tokyo 160 0023, Japan
    Jpn J Clin Oncol 39:509-13. 2009
    Polycythemia vera (PV) is a clonal myeloproliferative neoplasia associated with the activation of the Janus-activating kinase 2 (JAK2) mutation. The aim of this study is to identify clonal expansion of exon 12 mutations.
  61. pmc JAK2V617F allele burden and thrombosis: a direct comparison in essential thrombocythemia and polycythemia vera
    Alessandra Carobbio
    Hematology Department, Ospedali Riuniti di Bergamo, Bergamo, Italy
    Exp Hematol 37:1016-21. 2009
    ..A direct comparison of the incidence and risk factors of major thrombosis in essential thrombocythemia (ET) and polycythemia vera (PV) according to their respective JAK2V617F allele burden is the object of this study...
  62. pmc Kinase domain mutations confer resistance to novel inhibitors targeting JAK2V617F in myeloproliferative neoplasms
    A Deshpande
    Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA, USA
    Leukemia 26:708-15. 2012
    ..Several small molecule drugs targeting JAK2 are currently in clinical development for treatment in these diseases...
  63. pmc Identification of an acquired JAK2 mutation in polycythemia vera
    Runxiang Zhao
    Hematology Oncology Division, Department of Medicine, Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Biol Chem 280:22788-92. 2005
    ..the entire coding regions of cDNAs of candidate enzymes, we identified a G:C--> T:A point mutation of the JAK2 tyrosine kinase in 20 of 24 PV blood samples but none in 12 normal samples...
  64. doi [JAK2 V617F and exon 12 genetic variations in Korean patients with BCR/ABL1-negative myeloproliferative neoplasms]
    Jeong Tae Kim
    Department of Laboratory Medicine, Chonbuk National University Medical School, Jeonju, Korea
    Korean J Lab Med 30:567-74. 2010
    b>JAK2 genetic variations have been described in a high proportion of patients with BCR/ABL1-negative myeloproliferative neoplasms (MPN)...
  65. ncbi Interaction of Janus kinases JAK-1 and JAK-2 with the insulin receptor and the insulin-like growth factor-1 receptor
    P Gual
    Institut National de la Santé et de la Recherche Médicale U 145, Faculte de Medecine, Nice, France
    Endocrinology 139:884-93. 1998
    ....
  66. doi Molecular and clinical features of the myeloproliferative neoplasm associated with JAK2 exon 12 mutations
    Francesco Passamonti
    Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
    Blood 117:2813-6. 2011
    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...
  67. doi Molecular basis for pseudokinase-dependent autoinhibition of JAK2 tyrosine kinase
    Yibing Shan
    1 D E Shaw Research, New York, New York, USA 2
    Nat Struct Mol Biol 21:579-84. 2014
    Janus kinase-2 (JAK2) mediates signaling by various cytokines, including erythropoietin and growth hormone. JAK2 possesses tandem pseudokinase and tyrosine-kinase domains...
  68. doi The JAK2 exon 12 mutations: a comprehensive review
    Linda M Scott
    Greehey Children s Cancer Research Institute, University of Texas Health Sciences Center at San Antonio, San Antonio, Texas 78229, USA
    Am J Hematol 86:668-76. 2011
    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...
  69. ncbi JAK2V617F mutation is common in old patients with polycythemia vera and essential thrombocythemia
    Maria Luigia Randi
    Department of Medical and Surgical Sciences, University of Padova Medical School, Padova, Italy
    Aging Clin Exp Res 23:17-21. 2011
    ..JAK2V617F mutation occurs in 90% of polycythemia vera (PV) and in 50% of essential thrombocythemia (ET) patients...
  70. doi High percentage of JAK2 exon 12 mutation in Asian patients with polycythemia vera
    Yu Min Yeh
    Dept of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
    Am J Clin Pathol 134:266-70. 2010
    We examined the occurrence of JAK2(V617F) and JAK2 exon 12 mutations in a clinical cohort of polycythemia vera (PV) in Taiwan...
  71. pmc Janus kinase 2 regulates Bcr-Abl signaling in chronic myeloid leukemia
    A Samanta
    Department of Molecular Pathology, M D Anderson Cancer Center, Houston, TX 77054, USA
    Leukemia 25:463-72. 2011
    ..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...
  72. pmc Mechanistic insights into activation and SOCS3-mediated inhibition of myeloproliferative neoplasm-associated JAK2 mutants from biochemical and structural analyses
    Leila N Varghese
    School of Medicine, University of Tampere and Tampere University Hospital, Tampere 33014, Finland
    Biochem J 458:395-405. 2014
    b>JAK2 (Janus kinase 2) initiates the intracellular signalling cascade downstream of cell surface receptor activation by cognate haemopoietic cytokines, including erythropoietin and thrombopoietin...
  73. pmc Structure of the pseudokinase-kinase domains from protein kinase TYK2 reveals a mechanism for Janus kinase (JAK) autoinhibition
    Patrick J Lupardus
    Departments of Structural Biology and
    Proc Natl Acad Sci U S A 111:8025-30. 2014
    ..the TYK2 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...
  74. doi Impact of JAK2V617F mutation status, allele burden, and clearance after allogeneic stem cell transplantation for myelofibrosis
    Haefaa Alchalby
    Department of Stem Cell Transplantation, University Medical Center Hamburg Eppendorf, Martinistrasse 52, Hamburg, Germany
    Blood 116:3572-81. 2010
    ..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...
  75. pmc JAK2(V617F) allele burden in polycythemia vera correlates with grade of myelofibrosis, but is not substantially affected by therapy
    Richard T Silver
    Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY 10065 4896, USA
    Leuk Res 35:177-82. 2011
    In a series of 105 patients with polycythemia vera, we retrospectively determined whether the JAK2(V617F) mutation correlated with severity of disease phenotype...
  76. pmc Screening for hotspot mutations in PI3K, JAK2, FLT3 and NPM1 in patients with myelodysplastic syndromes
    João Agostinho Machado-Neto
    Hematology and Hemotherapy Center, National Institute of Blood, University of Campinas, Sao Paulo, Brazil
    Clinics (Sao Paulo) 66:793-9. 2011
    ..The accumulation of genetic alterations is closely associated with the progression of myelodysplastic syndromes toward acute myeloid leukemia...
  77. ncbi The gain-of-function JAK2 V617F mutation shifts the phenotype of essential thrombocythemia and chronic idiopathic myelofibrosis to more "erythremic" and less "thrombocythemic": a molecular, histologic, and clinical study
    Zbigniew Rudzki
    Department of Pathomorphology, Collegium Medicum, Jagiellonian University, Krakow, Poland
    Int J Hematol 86:130-6. 2007
    We investigated the prevalence of the JAK2 V617F gain-of-function mutation in patients with Philadelphia chromosome-negative chronic myeloproliferative disorders (Ph- MPD) and explored the links between JAK2 mutational status and the ..
  78. ncbi Prevalence of JAK2 V617F mutation in Indian patients with chronic myeloproliferative disorders
    Sudha Sazawal
    Department of Haematology, All India Institute of Medical Sciences, New Delhi, India
    Indian J Med Res 132:423-7. 2010
    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 ..
  79. ncbi Janus kinase 2 (V617F) mutation status, signal transducer and activator of transcription-3 phosphorylation and impaired neutrophil apoptosis in myelofibrosis with myeloid metaplasia
    R A Mesa
    Division of Hematology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    Leukemia 20:1800-8. 2006
    An activating point mutation in Janus kinase 2 (JAK2 V617F) was recently identified in myelofibrosis with myeloid metaplasia (MMM)...
  80. ncbi A t(8;9) translocation with PCM1-JAK2 fusion in a patient with T-cell lymphoma
    J Adelaide
    Leukemia 20:536-7. 2006
  81. ncbi JAK2 V617F is specifically associated with idiopathic splanchnic vein thrombosis
    S Regina
    J Thromb Haemost 5:859-61. 2007
  82. ncbi JAK2 mutation status, hemostatic risk factors and thrombophilic factors in essential thrombocythemia (ET) patients
    Bozena Sokołowska
    Department of Hematology, Medical University of Lublin, Poland
    Folia Histochem Cytobiol 49:267-71. 2011
    The recently discovered JAK2 V617F point mutation, found in 50-60% of ET patients, has been reported to be associated with a higher risk of thrombotic events...
  83. doi JAK pathway induction of c-Myc critical to IL-5 stimulation of cell proliferation and inhibition of apoptosis
    Wei Hwa Lee
    Department of Laboratory Medicine, Taipei Medical University Wan Fang Hospital, Taipei, Taiwan
    J Cell Biochem 106:929-36. 2009
    ..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)...
  84. pmc Bim and Mcl-1 exert key roles in regulating JAK2V617F cell survival
    Joëlle Rubert
    Disease Area Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland
    BMC Cancer 11:24. 2011
    ..It has previously been shown that activated JAK2 promotes cell survival by upregulating the anti-apoptotic STAT5 target gene Bcl-xL...
  85. ncbi JAK2V617F prevalence and allele burden in non-splanchnic venous thrombosis in the absence of overt myeloproliferative disorder
    A Pardanani
    Leukemia 21:1828-9. 2007
  86. ncbi The V617F mutation of JAK2 is very uncommon in patients with thrombosis
    Angel F Remacha
    Haematologica 92:285-6. 2007
    ..We investigated the V617F mutation of the JAK2 gene in 295 patients with thrombosis. Only one case was positive...
  87. ncbi Prevalence of the JAK2 V617F mutation is low among unselected patients with a first episode of unprovoked venous thromboembolism
    V Ugo
    J Thromb Haemost 6:203-5. 2008
  88. ncbi 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
    K Ohyashiki
    Leukemia 21:1097-9. 2007
  89. doi JAK2V617F activating mutation is associated with the myeloproliferative type of chronic myelomonocytic leukaemia
    A Pich
    Department of Biomedical Sciences and Human Oncology, Section of Pathology, University of Turin, Turin, Italy
    J Clin Pathol 62:798-801. 2009
    ..It is classified in the World Health Organization myeloproliferative-myelodysplastic overlap category. JAK2(V617F) mutation can be found in a large percentage of patients with myeloproliferative neoplasms.
  90. doi The JAK2 46/1 haplotype in Budd-Chiari syndrome and portal vein thrombosis
    Jasper H Smalberg
    Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands
    Blood 117:3968-73. 2011
    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)...
  91. pmc JAK2 exon 14 deletion in patients with chronic myeloproliferative neoplasms
    Wanlong Ma
    Department of Hematology Oncology, Quest Diagnostics Nichols Institute, San Juan Capistrano, California, USA
    PLoS ONE 5:e12165. 2010
    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...
  92. pmc The role of the JAK2 GGCC haplotype and the TET2 gene in familial myeloproliferative neoplasms
    Damla Olcaydu
    Center for Molecular Medicine, Austrian Academy of Sciences, Lazarettgasse 14, AKH BT25 3, 1090 Vienna, Austria
    Haematologica 96:367-74. 2011
    ..a group of diverse chronic myeloid malignancies that share pathogenic features such as acquired mutations in the JAK2, TET2, CBL and MPL genes...
  93. pmc The JAK2 46/1 haplotype predisposes to MPL-mutated myeloproliferative neoplasms
    Amy V Jones
    Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, United Kingdom
    Blood 115:4517-23. 2010
    The 46/1 JAK2 haplotype predisposes to V617F-positive myeloproliferative neoplasms, but the underlying mechanism is obscure...
  94. ncbi Simultaneous activation of JAK1 and JAK2 confers IL-3 independent growth on Ba/F3 pro-B cells
    Huei Mei Huang
    Graduate Institute of Cell and Molecular Biology, Center for Stem Cells Research at Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
    J Cell Biochem 96:361-75. 2005
    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...
  95. ncbi Role of the vav proto-oncogene product (Vav) in erythropoietin-mediated cell proliferation and phosphatidylinositol 3-kinase activity
    H Shigematsu
    Cancer Center and First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka 812, Japan
    J Biol Chem 272:14334-40. 1997
    ..Finally, we found that JAK2 was associated with Vav in vivo and that Vav could be tyrosine-phosphorylated by activated JAK2 in vitro...
  96. ncbi Inhibition and restoration of prolactin signal transduction by suppressors of cytokine signaling
    A Pezet
    INSERM U344, Faculte de Medecine Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France
    J Biol Chem 274:24497-502. 1999
    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 ..
  97. pmc Signal transducers and activators of transcription-3 binding to the fibroblast growth factor receptor is activated by receptor amplification
    Anna A Dudka
    CRUK Growth Factor Group, School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom
    Cancer Res 70:3391-401. 2010
    ..Our findings show that amplified FGFR expression engages the STAT3 pathway, and they suggest therapeutic strategies to attack FGFR-overexpressing cancers...
  98. pmc Sustained Src inhibition results in signal transducer and activator of transcription 3 (STAT3) activation and cancer cell survival via altered Janus-activated kinase-STAT3 binding
    Banibrata Sen
    Department of Thoracic Head and Neck Medical Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030 4009, USA
    Cancer Res 69:1958-65. 2009
    ..resulted in STAT3 activation showing specificity, which was inhibited by Janus-activated kinase (JAK; TYK2 and JAK2) depletion with siRNA...

Research Grants65

  1. Tyrosine Phosphatase PTP-MEG2 and Hematopoiesis
    ZHIZHUANG ZHAO; Fiscal Year: 2009
    ..Recently, we have made a major breakthrough in the study of PV by identifying a mutation of the JAK2 tyrosine kinase in over 80% of PV patients...
  2. Tyrosine Kinase JAK2 and Myeloproliferative Disorders
    Zhizhuang Joe Zhao; Fiscal Year: 2010
    ..Recently, we and others have identified a mutation in the JAK2 tyrosine kinases in classic MPDs including polycythemia vera (PV), essential thrombocythemia (ET), and primary ..
  3. MOLECULAR AND CELLULAR BIOLOGY OF THROMBOPOIETIN
    Kenneth Kaushansky; Fiscal Year: 2013
    ..with the c-Mpl receptor, TPO initiates a signaling cascade by triggering the phosphorylation and activation of Jak2. Although this is well established, it remains unclear as to how TPO signaling is modulated, which has important ..
  4. Role of JAK2V617F in the Pathogenesis of Myeloproliferative Disorders.
    Golam Mohi; Fiscal Year: 2013
    ..A somatic point mutation (V617F) in the Janus Kinase 2 (JAK2) has been found in majority of patients with polycythemia vera (PV), essential thrombocythemia (ET), and primary ..
  5. Role of Gab2 and Shp2 in Hematopoietic Signalling
    Benjamin G Neel; Fiscal Year: 2010
    ..g., leukemia-associated translocations that encode fusion-PTKs (e.g. Bcr/Abl, Tel-Jak2), or point mutations in PTKs, such as the V617F mutation in Jak2 found in many adult MPDs...
  6. AKT Signaling and Oxidative Stress Regulation of Erythropoiesis
    Saghi Ghaffari; Fiscal Year: 2013
    ..Signals generated from Erythropoietin (Epo) binding to its receptor erythropoietin receptor (EpoR) are mediated by JAK2 tyrosine kinase and are essential for normal erythroid cell development...
  7. Diagnostic Assay for Thrombocytosis
    Dmitri V Gnatenko; Fiscal Year: 2010
    ..b>Jak2 genetic testing offers some diagnostic value, but it does not have adequate specificity or selectivity...
  8. Predictors of therapeutic responsiveness to lestaurtinib in myelofibrosis
    Elizabeth O Hexner; Fiscal Year: 2012
    ..Recently, several groups identified a gain- of-function mutation in Janus Kinase 2 (JAK2 V617F) in the majority of patients with MPDs, suggesting that JAK2 is a potential therapeutic target in these ..
  9. CRLF2 signaling in B-cell acute lymphoblastic leukemia
    DAVID MARC WEINSTOCK; Fiscal Year: 2013
    ..based on the presence or absence of somatic mutations within either CRLF2 itself or the receptor-associated kinase JAK2. Our central hypothesis is that B-ALLs with CRLF2 overexpression are dependent on CRLF2 signaling for survival...
  10. Identification of novel target genes for polycythemia vera (PV)
    Shaoguang Li; Fiscal Year: 2013
    ..Recent discovery of the JAK2V617F mutation has promoted the development of targeted therapy using JAK2 inhibitors to inhibit the function of JAK2V617F...
  11. Inhibition of Histone Deacetylase in Myeloproliferative Neoplasms
    Golam Mohi; Fiscal Year: 2012
    ..A somatic point mutation (V617F) in the JAK2 tyrosine kinase has been detected in most patients with PV and 50-60% patients with ET and PMF...
  12. Molecular Pathogenesis & Therapy in JAK2 V617F Myeloproliferative Disease
    Virginia Zaleskas; Fiscal Year: 2009
    ..Recently, a somatic activating mutation (V617F) in the JAK2 tyrosine kinase was discovered in most patients with PV and some patients with ET and CIMF...
  13. Molecular Pathogenesis &Therapy of JAK2 V617F-induced Myeloproliferative Disease
    Richard A Van Etten; Fiscal Year: 2012
    ..Recently, a somatic activating mutation (V617F) in the JAK2 tyrosine kinase was discovered in most patients with PV and some patients with ET and CIMF...
  14. TSAD AS AN EPOR/JAK2 ADAPTOR AND ERYTHROPOIETIC REGULATOR
    DONALD JOSEPH MCCRANN; Fiscal Year: 2010
    ..goal of this application is to define roles of TSAD (T-cell specific adaptor protein) in a novel context of EPOR/JAK2 dependent erythropoiesis...
  15. Characterization of a Novel Erythropoietin Signaling Pathway
    Adam N Goldfarb; Fiscal Year: 2013
    ..In addition, the essential EpoR downstream mediators, JAK2 and PLC3, will be analyzed for their contributions to PKD activation...
  16. Mechanisms of tumor resistance to anti-HER/ErbB therapeutics
    Zhen Fan; Fiscal Year: 2012
    ..receptor family, EpoR homodimerizes upon EPO binding, triggering activation of the receptor-associated kinase Jak2, subsequent phosphorylation of STAT5, and a signal transduction cascade mediated by SH2 domain-containing adaptors ..
  17. Role of JAK2-PAK1 interaction in prolactin-dependent signaling
    Maria Diakonova; Fiscal Year: 2013
    ..Tyrosine (Tyr) kinase JAK2 was identified as a PRLR-bound signaling molecule...
  18. Growth Hormone Regulation of SH2B1
    Christin Carter-Su; Fiscal Year: 2013
    ..SH2B1 is recruited to JAK2 and is a critical component in GH regulation of the actin cytoskeleton, a prerequisite for cellular proliferation, ..
  19. Optimizing selective in vivo inhibition of pancreatic tumor JAK2/STAT3 signaling
    Mitch A Phelps; Fiscal Year: 2013
    ..Resulting data will be valuable for guiding further structural or formulation modifications to further enhance their activities and ultimately move them into clinical evaluation in patients with pancreatic cancer. ..
  20. GROWTH HORMONE RECEPTORS AND ACTIONS
    Christin Carter Su; Fiscal Year: 2010
    ..in understanding the molecular actions of growth hormone (GH) was the identification of the tyrosine (Tyr) kinase JAK2 as a receptor-associated signaling molecule for the GH receptor (GHR)...
  21. IL-6-mediated Jak2/Stat3 signaling and Brain Development
    Jun Tan; Fiscal Year: 2011
    ..Our preliminary studies showed that the citrus bioflavonoid, luteolin, inhibits neuronal JAK2/STAT3 phosphorylation in both murine neuron-like (N2a) cells and primary cultured neuronal cells challenged with ..
  22. Mechanisms of Regulation Of NHE-1
    John R Raymond; Fiscal Year: 2012
    ..This model will be tested in three specific aims: Aim #1: We will examine the role of Jak2-induced tyrosine phosphorylation of CaM in the activation of NHE-1...
  23. Targeting the JAK/STAT-3 Pathway Signaling Axis in Glioma
    Etty N Benveniste; Fiscal Year: 2013
    ..Importantly, STAT-3 was recently shown to be a master regulator of GBM aggressiveness. Janus Kinase 1 (JAK1) and JAK2, tyrosine kinases critical for STAT-3 activation, are also inappropriately activated in GBMs...
  24. TYROSINE PHOSPHORYLATION AND GROWTH HORMONE SIGNALING
    Stuart J Frank; Fiscal Year: 2013
    ..biological actions by interacting with GH receptor (GHR), which activates the cytoplasmic tyrosine kinase, JAK2, and signaling molecules including signal transducer and activator of transcription (STAT)-5...
  25. Role of JAK2 in Innate Immunity
    Richard J Lamont; Fiscal Year: 2013
    ..on the intracellular signaling pathways activated by TLR2 and have subsequently identified that the Janus Kinase 2 (JAK2) plays an essential role in controlling the innate inflammatory response...
  26. Molecular mechanisms of leptin receptor/Jak2 action
    Martin G Myers; Fiscal Year: 2013
    ..goals of our previous and proposed studies under this award, entitled, "Molecular Mechanisms of Leptin Receptor/Jak2 Action," are to understand mechanisms of LepRb signaling and how these signals regulate neural function to control ..
  27. Mnk Pathways and IFN-responses in Malignant Cells
    Leonidas C Platanias; Fiscal Year: 2013
    ..Jak kinases in the activation of Mnk 1/2 will be performed, while the potential regulatory effects of Jak2 on the function of nuclear Mnk2b and mRNA nuclear export will be determined...
  28. JAK2_STAT3 as a therapeutic target and marker of graft-versus-host disease
    Brian C Betts; Fiscal Year: 2013
    ..b>JAK2 inhibition induces allotolerance, while preserving Treg development...
  29. The role of signaling molecule AIP1 in pathological angiogenesis
    Wang Min; Fiscal Year: 2013
    ..its C-terminal CC/LZ domain competes with NEMO for the RIP1 association, disrupting IKK complex formation, and how JAK2/Bmx-SOCS3 mediates AIP1 phosphorylation and degradation during pathological angiogenesis...
  30. Dose-dependent Activation of the MEK/ERK Pathway in Hematopoiesis
    Jing Zhang; Fiscal Year: 2013
    ..through a dose-dependent activation of the MEK/ERK pathway;3) determine whether inhibition of MEK1/2 and Jak2 blocks Nras G12D/G12D-mediated MPD and its transformation to a blast crisis...
  31. Enhancement of Medullary Erythropoiesis during Anemia by Trib3
    David Kuhrt; Fiscal Year: 2013
    ..The Wojchowski laboratory identified Trib3 pseudokinase as a major EPO/Jak2/STAT5 target gene in erythroid lineage cells, and has established a Trib3-knockout (Trib3-KO) mouse model to ..
  32. Regulating Hematopoietic Stem Cell Homeostasis through GSK-3
    Wei Tong; Fiscal Year: 2013
    ..including Wnt signaling and cytokines such as Thrombopoietin (Tpo) and Erythropoietin, which signal through JAK2 to activate STAT5, Akt, and MAP kinase pathways...
  33. JAK2 signaling in erythropoiesis
    LILY JUNSHEN HUANG; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The Janus tyrosine kinase 2 (JAK2) plays an important role in hematopoiesis of multiple lineages, and a gain-of-function JAK2 mutation, V617F, is the major determinant in myeloproliferative neoplasms (..
  34. Erythropoietin receptor /Janus Kinase 2 complex
    Lily Huang; Fiscal Year: 2006
    ..The EpoR lacks intrinsic catalytic activity and relies on Janus Kinase 2 (JAK2) for signal transduction...
  35. Regulation of Cell Signaling by Human Biliverdin Reductase
    Mahin D Maines; Fiscal Year: 2013
    ..contains consensus sequences for binding STAT1 and Elk;and, in a yeast two-hybrid screening of high stringency, JAK2 kinase was identified as hBVR binding partner;hBVR, STAT1 and Elk are activated by cytokines...
  36. STRUCTURE/FUNCTION OF THE ERYTHROPOIETIN RECEPTOR
    STEPHEN SAWYER; Fiscal Year: 2003
    ..EPOR mediates its actions by interacting with the tyrosine protein kinase, JAK2. Preliminary evidence shows that the EPOR phosphorylated on serine residues selectively binds to the JAK2 kinase in ..
  37. ERYTHROPOIETIN-INDUCED NEUROPROTECTION
    Stuart Lipton; Fiscal Year: 2005
    ..prevents N-methyl-D aspartate (NMDA)- and NO-induced apoptosis by triggering cross talk between the Janus kinase-2 (Jak2) and nuclear factor KB (NF-KB) signaling pathways...
  38. Molecular Pathogenesis of MDS and CMML
    Jaroslaw P Maciejewski; Fiscal Year: 2013
    ..In particular areas of somatic UPD have been linked to the presence of biallelic mutations, such as Jak2 (UPD9p) and Ftl3 (UPD13q)...
  39. Leptin function &resistance in midbrain VTA &SN in reward eating &obesity
    YI NONE ZHANG; Fiscal Year: 2013
    ..Food consumption, body weight gain, and energy expenditure including locomotor activity will be examined along with JAK2-STAT3 and/or ERK leptin signaling...
  40. Growth Hormone Regulation of SH2-B1
    Christin Carter Su; Fiscal Year: 2009
    ..Upon GH binding, GHR-associated JAK2 is activated and phosphorylates tyrosines within JAK2 itself and GHR...
  41. SH2-B regulation of body weight and energy homeostasis
    Liangyou Rui; Fiscal Year: 2010
    ..LEPRb binds to and activates JAK2, a cytoplasmic tyrosine kinase that mediates key signaling pathways in response to leptin...
  42. Phosphodiesterase-3B signaling in the Hypothalamus and Obesity
    Abhiram Sahu; Fiscal Year: 2013
    ..Our study suggests that a PI3K-PDE3B-cAMP pathway interacting with the JAK2-STAT3 pathway constitutes a critical component of leptin signaling in the hypothalamus...
  43. The role of PTP1B in leptin receptor-dependent and -independent regulation of ene
    Ryan Tsou; Fiscal Year: 2013
    ..This pathway involves downstream activity by Janus kinase 2 (JAK2), a known substrate of PTP1B...
  44. PERINATAL METABOLIC AND HORMONAL EFFECTS
    Sherin U Devaskar; Fiscal Year: 2010
    ..a) leptin and insulin receptor cross-talk signaling pathways by assessing the ObRb-JAK2-STAT3/SOCS3-SHP2-PTP1B and the IRbeta tyrosine kinase-IRS1/2-P-l-3-kinase- PDK1/2-Akt1/2/PKC;-PDE38-cAMP pathways ..
  45. Vascular ANGII/Jak2 in progression of renal disease
    Peter P Sayeski; Fiscal Year: 2012
    ..is to establish the importance of the coupling between angiotensin II (ANGII) signaling and Janus kinase 2 (Jak2) in vascular smooth muscle cells (VSMC) in the progression of CKD...
  46. STUDIES IN GLAUCOMATOUS OPTIC NERVE DAMAGE
    John C Morrison; Fiscal Year: 2013
    ..Ruikang Wang at the University of Washington. Specific Aim 3 will demonstrate that inhibition of the Jak2/Stat3 pathway, an initial ONH responder to elevated IOP, can suppress downstream specific ONH gene expression ..
  47. Novel Strategy to Sensitize Prostate Cancer Cells to Radiation
    Marja T Nevalainen; Fiscal Year: 2013
    ..The proposed work has direct significance for therapy development for PCa since existing small-molecule Jak2-Stat5 inhibitors could become immediately available to prostate cancer patients as pharmacological tools for ..
  48. Growth Hormone Receptor Dimerization &Disulfide Linkage
    Stuart J Frank; Fiscal Year: 2013
    ..extracellular domain (ECD) and activates signaling via its intracellular domain's (ICD) interaction with the JAK2 tyrosine kinase...
  49. Architectural Basis of Leptin Transmembrane Signaling
    Georgios Skiniotis; Fiscal Year: 2013
    ..Complex formation between leptin and the extracellular portion of L-R results in the activation of Janus kinase 2 (JAK2) that is constitutively bound on the intracellular regions of the receptor...
  50. Stem cells in liver regeneration: fusion or plasticity
    Bryon E Petersen; Fiscal Year: 2013
    ..We will pursue the following specific aims: Specific Aim 1: We hypothesize that activation of the JAK2 and MAPK signal transduction pathways by G-CSF interaction with G-CSF receptor on the cell membrane enhances both ..
  51. Translational Insights into Estrogen Receptor alpha-Positive Luminal Breast Cance
    ROBERT DAVID SCHREIBER; Fiscal Year: 2013
    ..luminal) mammary tumors from STAT1-/- mice, placing special emphasis on defining the role(s) of the hyperactivated JAK2-STAT3/5 signaling pathway that is operative in these tumor cells, and in identifying differentially expressed ..
  52. Role of microRNAs in the regulation of CML stem cell survival and self renewal
    Danilo Perrotti; Fiscal Year: 2013
    ..e. BCR-ABL1 and Jak2) and phosphatases (i.e. PP2A) and this may depend on altered expression of specific microRNAs (miRs)...
  53. Growth hormone signaling and lipid metabolism in fatty liver disease
    ETHAN WEISS; Fiscal Year: 2013
    ..How these livers accumulate lipid remains unknown. GH signals through the Janus kinase 2 (JAK2)...
  54. Lnk Regulatory Functions in Hematopoietic Stem Cells
    Wei Tong; Fiscal Year: 2013
    ..signaling axis for HSC biology is thrombopoietin (TPO) and its receptor Mpl, signaling through Janus Kinase (JAK2). TPO-/- or Mpl-/- mice show diminished HSC self-renewal...
  55. Therapeutic Intervention of the JAK/STAT Pathway for Neuroinflammation
    Etty N Benveniste; Fiscal Year: 2013
    ..AZD1480 is a JAK1 and JAK2 inhibitor, and AZD5776 inhibits JAK1...
  56. The Role of Leptin in Susceptibility to Amebiasis
    Chelsea S Marie; Fiscal Year: 2013
    ..We will also test if the Q223R polymorphism alters activation of JAK2, SHP-2, STAT5 and STAT3 pathways through the leptin receptor...
  57. Neurotrophin Signaling in Multiple Myeloma
    Roger N Pearse; Fiscal Year: 2010
    ..Cep701 is a derivative of the indolcarbazole, K252a, with an IC50 of 3 nM for Trk and for Jak2. It specifically kills both primary MM cells and MM cell lines in culture, and inhibits growth of MM cell lines ..
  58. Functional and Molecular Dissection of Myeloproliferative Neoplasm Stem Cells
    Ann Mullally; Fiscal Year: 2013
    ..it remains an attractive therapeutic target in MPN, although efforts to target it directly using small molecule JAK2 kinase inhibitors have so far failed to selectively and consistently diminish the JAK2V617F mutant clone in MPN ..
  59. Modulation of tumor susceptibility to NK cells induced by JAK family genes
    Roberto Bellucci; Fiscal Year: 2012
    ..the genes that modulated target cell susceptibility to NK activity we found 2 members of the Jak family (Jak1 and Jak2)...
  60. Pathophysiological Redox Regulation of JAK2 in Diabetes
    ROY DUHE; Fiscal Year: 2009
    ..Due to JAK2's crucial role as a signal transducer for leptin, growth hormone, ciliary neurotrophic factor, stromal derived ..
  61. TRANSCRIPTION FACTOR REGULATION BY THE BCR/ABL ONCOGENE
    Bruno Calabretta; Fiscal Year: 2012
    ..c) effects of the c-Myb target Jak2 , individually and in cooperation with c-Kit, in transformation and leukemogenesis of p210BCR/ABL-expressing ..
  62. Genome-wide dissection of Mendelian susceptibility to mycobacterial disease
    Jean Laurent Casanova; Fiscal Year: 2013
    ..evidence of five novel MSMD-causing genes, with recessive mutations in X-linked CYBB and autosomal TYK2, JAK2, ISG15, and AP4E1...
  63. Tyrosine Phosphyorylation and Growth Hormone Signaling
    STUART FRANK; Fiscal Year: 2005
    ..receptors (GHR; PRLR), both cytokine receptors, causing activation of the GHR- and PRLR-associated tyrosine kinase, JAK2, and the STATS and ERK pathways...
  64. Cytokine Signaling in Autoimmune APC Dysfunction
    Sally Litherland; Fiscal Year: 2005
    ..Like many cytokines involved in hematopoiesis, GM-CSF uses the JAK2-STAT5 signal transduction/transcriptional regulatory pathway to exert its control over cellular functions...
  65. SRC-LIKE KINASES IN INTERLEUKIN-3 RECEPTOR SIGNALING
    Steven Anderson; Fiscal Year: 2001
    ..It appears that the activation of JAK2 and STAT molecules may be necessary, but not sufficient, for GM-CSF-induced mitogenesis...