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

Top Publications

  1. ncbi Involvement of protein phosphatase 2A in the interleukin-3-stimulated Jak2-Stat5 signaling pathway
    N Yokoyama
    Department of Physiology and Biophysics, School of Medicine, State University of New York at Stony Brook, Stony Brook, NY 11794 8661, USA
    J Interferon Cytokine Res 21:369-78. 2001
  2. ncbi Involvement of Jak2 tyrosine phosphorylation in Bcr-Abl transformation
    S Xie
    Department of Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Oncogene 20:6188-95. 2001
  3. 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
  4. ncbi A gain-of-function mutation of JAK2 in myeloproliferative disorders
    Robert Kralovics
    Department of Research, Experimental Hematology, University Hospital Basel, Basel, Switzerland
    N Engl J Med 352:1779-90. 2005
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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

Research Grants

  1. Tyrosine Phosphatase PTP-MEG2 and Hematopoiesis
    ZHIZHUANG ZHAO; Fiscal Year: 2009
  2. Tyrosine Kinase JAK2 and Myeloproliferative Disorders
    Zhizhuang Joe Zhao; Fiscal Year: 2010
  3. MOLECULAR AND CELLULAR BIOLOGY OF THROMBOPOIETIN
    Kenneth Kaushansky; Fiscal Year: 2013
  4. Golam Mohi; Fiscal Year: 2016
  5. Role of Gab2 and Shp2 in Hematopoietic Signalling
    Benjamin G Neel; Fiscal Year: 2010
  6. Inhibition of Histone Deacetylase in Myeloproliferative Neoplasms
    Golam Mohi; Fiscal Year: 2012
  7. Diagnostic Assay for Thrombocytosis
    Dmitri V Gnatenko; Fiscal Year: 2010
  8. Predictors of therapeutic responsiveness to lestaurtinib in myelofibrosis
    Elizabeth O Hexner; Fiscal Year: 2012
  9. DAVID MARC WEINSTOCK; Fiscal Year: 2016
  10. AKT Signaling and Oxidative Stress Regulation of Erythropoiesis
    Saghi Ghaffari; Fiscal Year: 2013

Detail Information

Publications337 found, 100 shown here

  1. ncbi Involvement of protein phosphatase 2A in the interleukin-3-stimulated Jak2-Stat5 signaling pathway
    N Yokoyama
    Department of Physiology and Biophysics, School of Medicine, State University of New York at Stony Brook, Stony Brook, NY 11794 8661, USA
    J Interferon Cytokine Res 21:369-78. 2001
    In this study, we report that the tyrosine kinase, Janus kinase 2 (Jak2), associates with the serine/threonine protein phosphatase 2A (PP2A) in 32Dcl3 myeloid progenitor cells...
  2. ncbi Involvement of Jak2 tyrosine phosphorylation in Bcr-Abl transformation
    S Xie
    Department of Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Oncogene 20:6188-95. 2001
    We have previously reported that the Jak2 tyrosine kinase but not Jak1 is tyrosine phosphorylated in the absence of IL-3 in Bcr-Abl positive M3.16 cells, which are rendered IL-3 independent by BCR-ABL gene expression...
  3. 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...
  4. ncbi A gain-of-function mutation of JAK2 in myeloproliferative disorders
    Robert Kralovics
    Department of Research, Experimental Hematology, University Hospital Basel, Basel, Switzerland
    N Engl J Med 352:1779-90. 2005
    ..The loss of heterozygosity (LOH) on the short arm of chromosome 9 (9pLOH) in myeloproliferative disorders suggests that 9p harbors a mutation that contributes to the cause of clonal expansion of hematopoietic cells in these diseases...
  5. 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...
  6. 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 ..
  7. 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...
  8. 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...
  9. 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...
  10. 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...
  11. doi The influence of novel transcriptional regulatory element in intron 14 on the expression of Janus kinase 2 gene in myeloproliferative neoplasms
    Vesna Spasovski
    Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
    J Appl Genet 54:21-6. 2013
    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...
  12. 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 ..
  13. 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-..
  14. 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...
  15. 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 ..
  16. 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...
  17. 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...
  18. 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 ..
  19. 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)...
  20. 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...
  21. 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 ..
  22. 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...
  23. 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...
  24. 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
    ....
  25. 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...
  26. 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.
  27. 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...
  28. 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...
  29. 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...
  30. 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...
  31. 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...
  32. pmc 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...
  33. 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)...
  34. 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
  35. 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.
  36. 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...
  37. ncbi Tec tyrosine kinase links the cytokine receptors to PI-3 kinase probably through JAK
    M Takahashi-Tezuka
    Department of Molecular Oncology, Biomedical Research Center, Osaka University Medical School, Suita, Japan
    Oncogene 14:2273-82. 1997
    ..Here we show the association between Jak1/Jak2 and Tec or Jak1 and Btk. Furthermore, Jak1 but not Jak2 induces tyrosine phosphorylation of Btk, but not Tec...
  38. 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...
  39. 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...
  40. 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...
  41. doi SOCS-mediated downregulation of mutant Jak2 (V617F, T875N and K539L) counteracts cytokine-independent signaling
    S Haan
    Life Sciences Research Unit, University of Luxembourg, Luxembourg, Luxembourg
    Oncogene 28:3069-80. 2009
    Recently, mutations in the gene of Janus kinase 2 (Jak2) were discovered in patients suffering from chronic myeloproliferative disorders (MPD) and leukemia...
  42. ncbi Activated Jak2 with the V617F point mutation promotes G1/S phase transition
    Christoph Walz
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    J Biol Chem 281:18177-83. 2006
    ..The V617F activating point mutation in Jak2 has recently been associated with myeloproliferative disorders...
  43. pmc Suppression of cytokine signaling by SOCS3: characterization of the mode of inhibition and the basis of its specificity
    Jeffrey J Babon
    Walter and Eliza Hall Institute of Medical Research, 1G Royal Pde, Parkville, 3052, Vic, Australia
    Immunity 36:239-50. 2012
    ..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...
  44. 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)...
  45. 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...
  46. ncbi Jak2 is involved in c-Myc induction by Bcr-Abl
    Shanhai Xie
    Department of Molecular Pathology, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Houston, Texas, TX 77030, USA
    Oncogene 21:7137-46. 2002
    We have previously shown that the Jak2 tyrosine kinase is activated in Bcr-Abl positive cell lines and blood cells from CML blast crisis patients by tyrosine phosphorylation...
  47. 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.
  48. doi JAK2 stimulates homologous recombination and genetic instability: potential implication in the heterogeneity of myeloproliferative disorders
    Isabelle Plo
    INSERM, Unités Mixtes de Recherche 790, Villejuif, France
    Blood 112:1402-12. 2008
    The JAK2(V617F) mutation is frequently observed in classical myeloproliferative disorders, and disease progression is associated with a biallelic acquisition of the mutation occurring by mitotic recombination...
  49. pmc JAK mutations in high-risk childhood acute lymphoblastic leukemia
    Charles G Mullighan
    Departments of Pathology and Biostatistics, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Proc Natl Acad Sci U S A 106:9414-8. 2009
    ..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...
  50. ncbi JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin
    B A Witthuhn
    Department of Biochemistry, St Jude Children s Research Hospital, Memphis, Tennessee 38105
    Cell 74:227-36. 1993
    ..Here we demonstrate that EPO induces tyrosine phosphorylation of JAK2 kinase and activates its in vitro autophosphorylation...
  51. ncbi The t(4;22)(q12;q11) in atypical chronic myeloid leukaemia fuses BCR to PDGFRA
    E Joanna Baxter
    Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury SP2 8BJ, UK
    Hum Mol Genet 11:1391-7. 2002
    ..Our findings indicate that apparently simple cytogenetic variants of t(9;22) do not always mask a cryptic BCR-ABL fusion, even when found in association with clinical and haematological indications of CML...
  52. ncbi JAK2 mutation in essential thrombocythaemia: clinical associations and long-term prognostic relevance
    Alexandra P Wolanskyj
    Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA
    Br J Haematol 131:208-13. 2005
    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...
  53. ncbi Polycythemia vera is not initiated by JAK2V617F mutation
    Roberto H Nussenzveig
    Department of Leukemia, University of Texas, M D Anderson Cancer Center, Houston, TX, USA
    Exp Hematol 35:32-8. 2007
    The somatic JAK2(V617F) mutation is seen in most polycythemia vera (PV) patients; however, it is not clear if JAK2(V617F) is the PV-initiating mutation.
  54. pmc The Jak2V617F oncogene associated with myeloproliferative diseases requires a functional FERM domain for transformation and for expression of the Myc and Pim proto-oncogenes
    Gerlinde Wernig
    Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Blood 111:3751-9. 2008
    The V617F activating point mutation in Jak2 is associated with a proportion of myeloproliferative disorders...
  55. 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 ..
  56. 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)...
  57. 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)...
  58. pmc Molecular pathways: Jak/STAT pathway: mutations, inhibitors, and resistance
    Alfonso Quintas-Cardama
    Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
    Clin Cancer Res 19:1933-40. 2013
    ..a large proportion of patients with myeloproliferative neoplasms (MPN) carry the acquired gain-of-function JAK2 V617F somatic mutation...
  59. ncbi V617F mutation in JAK2 is associated with poorer survival in idiopathic myelofibrosis
    Peter J Campbell
    Department of Haematology, University of Cambridge, United Kingdom
    Blood 107:2098-100. 2006
    ..vera and half with idiopathic myelofibrosis and essential thrombocythemia have an acquired V617F mutation in JAK2. Using sensitive polymerase chain reaction (PCR)-based methods, we genotyped 152 patients with idiopathic ..
  60. doi JAK2V617F mutation screening as part of the hypercoagulable work-up in the absence of splanchnic venous thrombosis or overt myeloproliferative neoplasm: assessment of value in a series of 664 consecutive patients
    Animesh Pardanani
    Division of Hematology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
    Mayo Clin Proc 83:457-9. 2008
    ..Our study also suggests that the natural history of a JAK2V617F-positive "occult" MPN might be different from that of a typical MPN...
  61. doi Mutations of JAK2 in acute lymphoblastic leukaemias associated with Down's syndrome
    Dani Bercovich
    Human Molecular Genetics and Pharmacogenetics Laboratory, Migal Galilee Biotechnology Centre, Kiryat Shmona, and Tel Hai Academic College, Israel
    Lancet 372:1484-92. 2008
    ..We tested the hypothesis that mutations in JAK2 might be a common molecular event in acute lymphoblastic leukaemia associated with Down's syndrome.
  62. doi Effects of the JAK2 mutation on the hematopoietic stem and progenitor compartment in human myeloproliferative neoplasms
    Shubha Anand
    Department of Haematology, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, UK
    Blood 118:177-81. 2011
    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...
  63. pmc The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop
    H Yasukawa
    Institute of Life Science, Kurume University, Aikawa machi 2432 3 Kurume 839 0861, Japan
    EMBO J 18:1309-20. 1999
    ..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...
  64. ncbi The structural basis of Janus kinase 2 inhibition by a potent and specific pan-Janus kinase inhibitor
    Isabelle S Lucet
    Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia
    Blood 107:176-83. 2006
    b>JAK2, a member of the Janus kinase (JAK) family of protein tyrosine kinases (PTKs), is an important intracellular mediator of cytokine signaling...
  65. ncbi Prevalence of the activating JAK2 tyrosine kinase mutation V617F in the Budd-Chiari syndrome
    Raj K Patel
    Department of Haematological Medicine, King s College Hospital, London, England
    Gastroenterology 130:2031-8. 2006
    ..A clonal mutation in JAK2 tyrosine kinase (JAK2V617F) occurs in a high proportion of patients with MPD and is of use in the characterization ..
  66. ncbi A role for JAK2 mutations in myeloproliferative diseases
    Kelly J Morgan
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Annu Rev Med 59:213-22. 2008
    ..The JAK2V617F mutation alters the JAK2 tyrosine kinase to confer constitutive activation and affect downstream signaling pathways...
  67. doi Characteristics and clinical correlates of MPL 515W>L/K mutation in essential thrombocythemia
    Alessandro M Vannucchi
    Unita Funzionale di Ematologia, Dipartimento di Area Critica Medico Chirurgica, Universita degli Studi, Florence, Italy
    Blood 112:844-7. 2008
    ..These data indicate that MPLW515L/K mutations do not define a distinct phenotype in ET, although some differences depended on the JAK2V617F mutational status of the counterpart...
  68. doi The saga of JAK2 mutations and translocations in hematologic disorders: pathogenesis, diagnostic and therapeutic prospects, and revised World Health Organization diagnostic criteria for myeloproliferative neoplasms
    Cristina A Smith
    Department of Pathology, Oregon Health and Science University, Portland, OR 97239, USA
    Hum Pathol 39:795-810. 2008
    b>JAK2 is a tyrosine kinase involved in cytokine signaling...
  69. pmc Detection of JAK2 exon 12 mutations in 15 patients with JAK2V617F negative polycythemia vera
    Susanne Schnittger
    MLL, Munich Leukemia Laboratory, Max Lebsche Platz 31, 81377 Munich, Germany
    Haematologica 94:414-8. 2009
    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...
  70. pmc ID1 promotes expansion and survival of primary erythroid cells and is a target of JAK2V617F-STAT5 signaling
    Andrew D Wood
    Department of Hematology, Cambridge Institute for Medical Research, Addenbrooke s Hospital, Cambridge, United Kingdom
    Blood 114:1820-30. 2009
    ..an acquired mutation in the majority of patients with myeloproliferative disorders (MPDs) and the key role of the JAK2-STAT5 signaling cascade in normal hematopoiesis has focused attention on the downstream transcriptional targets of ..
  71. doi Clinical utility of routine MPL exon 10 analysis in the diagnosis of essential thrombocythaemia and primary myelofibrosis
    Elaine M Boyd
    Department of Haematology, Haemato Oncology Diagnostic Service, Addenbrooke s Hospital, Cambridge, UK
    Br J Haematol 149:250-7. 2010
    Approximately 50% of essential thrombocythaemia and primary myelo-fibrosis patients do not have a JAK2 V617F mutation...
  72. doi JAK2 rearrangements, including the novel SEC31A-JAK2 fusion, are recurrent in classical Hodgkin lymphoma
    Katrien Van Roosbroeck
    Center for Human Genetics, Katholieke Universiteit Leuven, Leuven, Belgium
    Blood 117:4056-64. 2011
    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 ..
  73. doi Human gastrin mRNA expression up-regulated by Helicobacter pylori CagA through MEK/ERK and JAK2-signaling pathways in gastric cancer cells
    Jianjiang Zhou
    Affiliated Hospital, Guiyang Medical University, No 9 Beijiang Road, Guiyang, China
    Gastric Cancer 14:322-31. 2011
    ..Helicobacter pylori-cytotoxin-associated protein A (CagA) and gastrin are believed to play an important role in gastric carcinogenesis, but their interaction has been incompletely clear...
  74. pmc Hepatocyte nuclear factor 4 response to injury involves a rapid decrease in DNA binding and transactivation via a JAK2 signal transduction pathway
    Xuemei Li
    Boston Medical Center, Department of Surgery, Boston, MA 02118, USA
    Biochem J 368:203-11. 2002
    ..The mechanisms by which HNF-4 is modified after injury involve the activation of Janus kinase 2 (JAK2) signal transduction pathways, but the direct or indirect interaction of JAK2 with HNF-4 remains to be defined.
  75. ncbi Cytokine-inducible SH2 protein-3 (CIS3/SOCS3) inhibits Janus tyrosine kinase by binding through the N-terminal kinase inhibitory region as well as SH2 domain
    A Sasaki
    Institute of Life Science, Kurume University, Aikawa machi 2432 3 Kurume 839 0861, Japan
    Genes Cells 4:339-51. 1999
    ..JAB inhibits JAK2 tyrosine kinase activity by binding to the kinase domain (JH1 domain) through the N-terminal kinase inhibitory ..
  76. ncbi Phosphorylation of STAT-3 in response to basic fibroblast growth factor occurs through a mechanism involving platelet-activating factor, JAK-2, and Src in human umbilical vein endothelial cells. Evidence for a dual kinase mechanism
    Dayanand D Deo
    Department of Biochemistry and Molecular Biology, Stanley S Scott Cancer Center and Neuroscience Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
    J Biol Chem 277:21237-45. 2002
    ..Taken together, these findings suggest the production of PAF is important for bFGF-mediated signaling and that a dual kinase mechanism is involved in the PAF-mediated signal transduction cascade...
  77. ncbi The pseudokinase domain is required for suppression of basal activity of Jak2 and Jak3 tyrosine kinases and for cytokine-inducible activation of signal transduction
    Pipsa Saharinen
    Haartman Institute, Department of Virology, Biomedicum Helsinki, Programme for Developmental and Reproductive Biology, University of Helsinki, Finland
    J Biol Chem 277:47954-63. 2002
    ..Here, we found that the JH2 domain negatively regulates the activity of Jak2 and Jak3...
  78. ncbi Tissue microarray analysis of signal transducers and activators of transcription 3 (Stat3) and phospho-Stat3 (Tyr705) in node-negative breast cancer shows nuclear localization is associated with a better prognosis
    Marisa Dolled-Filhart
    Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    Clin Cancer Res 9:594-600. 2003
    ....
  79. ncbi The cross-talk between angiotensin and insulin differentially affects phosphatidylinositol 3-kinase- and mitogen-activated protein kinase-mediated signaling in rat heart: implications for insulin resistance
    Jose B C Carvalheira
    Departamento de Clinica Medica, Faculdade de Ciencias Medicas, Universidade Estadual de Campinas, Cidade Universitaria Zeferino Vaz, Campinas, Sao Paulo 13081 970, Brazil
    Endocrinology 144:5604-14. 2003
    ..Thus, the imbalance between PI 3-kinase-Akt and MAPK signaling pathways in the heart may play a role in the development of cardiovascular abnormalities observed in insulin-resistant states, such as in obese Zucker rats...
  80. pmc Progestins induce transcriptional activation of signal transducer and activator of transcription 3 (Stat3) via a Jak- and Src-dependent mechanism in breast cancer cells
    Cecilia Proietti
    Instituto de Biología y Medicina Experimental IBYME, CONICET, Buenos Aires 1428, Argentina
    Mol Cell Biol 25:4826-40. 2005
    ..In addition, MPA induced rapid, nongenomic Stat3, Jak1, and Jak2 tyrosine phosphorylation in C4HD and T47D cells...
  81. ncbi The JAK2 V617F mutation identifies a subgroup of MDS patients with isolated deletion 5q and a proliferative bone marrow
    W Ingram
    Leukemia 20:1319-21. 2006
  82. ncbi Evidence that the JAK2 G1849T (V617F) mutation occurs in a lymphomyeloid progenitor in polycythemia vera and idiopathic myelofibrosis
    Francois Delhommeau
    INSERM U790, Université Paris Sud Institut Gustave Roussy, Pavillon de Recherche 1, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France
    Blood 109:71-7. 2007
    The JAK2 V617F mutation has recently been described as an essential oncogenic event associated with polycythemia vera (PV), idiopathic myelofibrosis (IMF), and essential thrombocythemia...
  83. ncbi Receptor-mediated tobacco toxicity: cooperation of the Ras/Raf-1/MEK1/ERK and JAK-2/STAT-3 pathways downstream of alpha7 nicotinic receptor in oral keratinocytes
    Juan Arredondo
    Department of Dermatology, University of California Davis, Sacramento, CA, USA
    FASEB J 20:2093-101. 2006
    ....
  84. pmc JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis
    Linda M Scott
    University of Cambridge, Cambridge, United Kingdom
    N Engl J Med 356:459-68. 2007
    ..which causes the substitution of phenylalanine for valine at position 617 of the Janus kinase (JAK) 2 gene (JAK2), is often present in patients with polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis...
  85. ncbi A simple, rapid, and sensitive method for the detection of the JAK2 V617F mutation
    Angela Y C Tan
    Department of Pathology, Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
    Am J Clin Pathol 127:977-81. 2007
    The point mutation 1849 (GT) V617F in the JAK2 gene occurs at high frequency in several chronic myeloproliferative diseases...
  86. ncbi JAK2-V617F mutation analysis of granulocytes and platelets from patients with chronic myeloproliferative disorders: advantage of studying platelets
    Kohtaro Toyama
    Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Gunma, Japan
    Br J Haematol 139:64-9. 2007
    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...
  87. doi Clonal heterogeneity in polycythemia vera patients with JAK2 exon12 and JAK2-V617F mutations
    Sai Li
    Department of Research, Experimental Hematology, University Hospital Basel, Switzerland
    Blood 111:3863-6. 2008
    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...
  88. 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...
  89. 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 ..
  90. 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...
  91. pmc Expression of a homodimeric type I cytokine receptor is required for JAK2V617F-mediated transformation
    Xiaohui Lu
    Whitehead Institute for Biomedical Research and the Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 102:18962-7. 2005
    A recurrent somatic activating mutation in the nonreceptor tyrosine kinase JAK2 (JAK2V617F) occurs in the majority of patients with the myeloproliferative disorders polycythemia vera, essential thrombocythemia, myelofibrosis with myeloid ..
  92. ncbi Involvement of various hematopoietic-cell lineages by the JAK2V617F mutation in polycythemia vera
    Takefumi Ishii
    Section of Hematology Oncology, University of Illinois College of Medicine, 909 S Wolcott Ave, COMRB, Rm 5035 M C 704, Chicago, IL 60612, USA
    Blood 108:3128-34. 2006
    The JAK2(V617F) mutation has been shown to occur in the overwhelming majority of patients with polycythemia vera (PV)...
  93. pmc JAK2T875N is a novel activating mutation that results in myeloproliferative disease with features of megakaryoblastic leukemia in a murine bone marrow transplantation model
    Thomas Mercher
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Blood 108:2770-9. 2006
    ..These findings provide new insights into pathways and therapeutic targets that contribute to the pathogenesis of AMKL...
  94. ncbi MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients
    Animesh D Pardanani
    Division of Hematology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
    Blood 108:3472-6. 2006
    ..Furthermore, MPL mutations may occur concurrently with the JAK2V617F mutation, suggesting that these alleles may have functional complementation in myeloproliferative disease...
  95. ncbi Incidence of the JAK2 V617F mutation among patients with splanchnic or cerebral venous thrombosis and without overt chronic myeloproliferative disorders
    V De Stefano
    Institute of Hematology, Catholic University, Rome, Italy
    J Thromb Haemost 5:708-14. 2007
    ..The recently identified Janus kinase 2 (JAK2) V617F somatic mutation is closely related to chronic myeloproliferative disorders (CMD).
  96. 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)...
  97. ncbi JAK2 V617F is specifically associated with idiopathic splanchnic vein thrombosis
    S Regina
    J Thromb Haemost 5:859-61. 2007

Research Grants70

  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. Golam Mohi; Fiscal Year: 2016
    ..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. 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...
  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. DAVID MARC WEINSTOCK; Fiscal Year: 2016
    ..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. 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...
  11. 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...
  12. 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...
  13. 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...
  14. Maria Diakonova; Fiscal Year: 2014
    ..Tyrosine (Tyr) kinase JAK2 was identified as a PRLR-bound signaling molecule...
  15. Christin Carter-Su; Fiscal Year: 2016
    ..SH2B1 is recruited to JAK2 and is a critical component in GH regulation of the actin cytoskeleton, a prerequisite for cellular proliferation, ..
  16. 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...
  17. 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...
  18. Mitch A Phelps; Fiscal Year: 2014
    ..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. ..
  19. 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)...
  20. 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 ..
  21. 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...
  22. Etty N Benveniste; Fiscal Year: 2016
    ..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...
  23. 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 ..
  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. Richard J Lamont; Fiscal Year: 2016
    ..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. Martin G Myers; Fiscal Year: 2016
    ..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. Leonidas C Platanias; Fiscal Year: 2015
    ..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. Brian C Betts; Fiscal Year: 2016
    ..b>JAK2 inhibition induces allotolerance, while preserving Treg development...
  29. Wang Min; Fiscal Year: 2016
    ..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. Jing Zhang; Fiscal Year: 2016
    ..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. 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...
  32. Mahin D Maines; Fiscal Year: 2015
    ..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...
  33. 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 ..
  34. 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...
  35. 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)...
  36. 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...
  37. 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...
  38. 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...
  39. 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...
  40. David Kuhrt; Fiscal Year: 2015
    ..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 ..
  41. 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...
  42. 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 ..
  43. 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...
  44. John C Morrison; Fiscal Year: 2016
    ..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 ..
  45. Wei Tong; Fiscal Year: 2014
    ..including Wnt signaling and cytokines such as Thrombopoietin (Tpo) and Erythropoietin, which signal through JAK2 to activate STAT5, Akt, and MAP kinase pathways...
  46. Marja T Nevalainen; Fiscal Year: 2014
    ..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 ..
  47. Stuart J Frank; Fiscal Year: 2014
    ..extracellular domain (ECD) and activates signaling via its intracellular domain's (ICD) interaction with the JAK2 tyrosine kinase...
  48. Georgios Skiniotis; Fiscal Year: 2016
    ..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...
  49. 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 ..
  50. 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 ..
  51. Danilo Perrotti; Fiscal Year: 2016
    ..e. BCR-ABL1 and Jak2) and phosphatases (i.e. PP2A) and this may depend on altered expression of specific microRNAs (miRs)...
  52. LILY JUNSHEN HUANG; Fiscal Year: 2016
    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 (..
  53. ETHAN WEISS; Fiscal Year: 2015
    ..How these livers accumulate lipid remains unknown. GH signals through the Janus kinase 2 (JAK2)...
  54. Wei Tong; Fiscal Year: 2016
    ..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. Etty N Benveniste; Fiscal Year: 2016
    ..AZD1480 is a JAK1 and JAK2 inhibitor, and AZD5776 inhibits JAK1...
  56. Chelsea S Marie; Fiscal Year: 2015
    ..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. Ann Mullally; Fiscal Year: 2015
    ..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. Jean Laurent Casanova; Fiscal Year: 2016
    ..evidence of five novel MSMD-causing genes, with recessive mutations in X-linked CYBB and autosomal TYK2, JAK2, ISG15, and AP4E1...
  63. JAMES DOUGLAS GRIFFIN; Fiscal Year: 2016
    ..and to implement novel therapies as they are developed and validated in the other projects, including, for example, JAK2 inhibitors for treatment of MPD...
  64. John D Crispino; Fiscal Year: 2016
    ..in DS leukemia, this research is also relevant to other leukemias with acquired trisomy 21, such as hyperdiploid ALL and to myeloproliferative neoplasms, in particular the large group of ET and PMF cases that lack JAK2 or MPL mutations.
  65. Regulation of Leptin Signaling
    Gen Sheng Feng; Fiscal Year: 2010
    ..overcome obesity and enhance leptin sensitivity, based on in vitro data showing a negative effect of Shp2 on the Jak2/Stat3 pathway...
  66. Umut Ozcan; Fiscal Year: 2016
    ..Furthermore, we will also determine whether any post-translational modifications created on LepRb and/or Jak2 by ER stress that reduces their activity...
  67. Anti-inflammatory, cholesterol export, and cardioprotective functions of ABCA1
    Renee C LeBoeuf; Fiscal Year: 2013
    ..We found that ABCA1 also functions as an anti-inflammatory signaling receptor through activation of a JAK2/STAT3 pathway, which is independent of cholesterol export activity...
  68. 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...
  69. 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...
  70. 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...