Jak2

Summary

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

Top Publications

  1. ncbi A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera
    Chloe James
    INSERM U362, Institut Gustave Roussy, Paris XI University, PR1, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France
    Nature 434:1144-8. 2005
  2. 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
  3. 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
  4. 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
  5. doi Mutation in TET2 in myeloid cancers
    Francois Delhommeau
    INSERM U790, Institut Gustave Roussy, Villejuif, France
    N Engl J Med 360:2289-301. 2009
  6. pmc JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin
    Mark A Dawson
    Cambridge Institute for Medical Research and Department of Haematology, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK
    Nature 461:819-22. 2009
  7. 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
  8. pmc IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic- or blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis
    A Tefferi
    Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA
    Leukemia 24:1302-9. 2010
  9. ncbi A prospective study of 338 patients with polycythemia vera: the impact of JAK2 (V617F) allele burden and leukocytosis on fibrotic or leukemic disease transformation and vascular complications
    F Passamonti
    Division of Hematology, Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
    Leukemia 24:1574-9. 2010
  10. 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

Detail Information

Publications277 found, 100 shown here

  1. ncbi A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera
    Chloe James
    INSERM U362, Institut Gustave Roussy, Paris XI University, PR1, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France
    Nature 434:1144-8. 2005
    ..Here, we describe a clonal and recurrent mutation in the JH2 pseudo-kinase domain of the Janus kinase 2 (JAK2) gene in most (> 80%) polycythaemia vera patients...
  2. 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...
  3. 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.
  4. 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...
  5. 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...
  6. pmc JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin
    Mark A Dawson
    Cambridge Institute for Medical Research and Department of Haematology, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK
    Nature 461:819-22. 2009
    Activation of Janus kinase 2 (JAK2) by chromosomal translocations or point mutations is a frequent event in haematological malignancies...
  7. 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...
  8. pmc IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic- or blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis
    A Tefferi
    Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA
    Leukemia 24:1302-9. 2010
    ..6%) blast-phase MPN (P<0.01). Mutant IDH was documented in the presence or absence of JAK2, MPL and TET2 mutations, with similar mutational frequencies...
  9. ncbi A prospective study of 338 patients with polycythemia vera: the impact of JAK2 (V617F) allele burden and leukocytosis on fibrotic or leukemic disease transformation and vascular complications
    F Passamonti
    Division of Hematology, Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
    Leukemia 24:1574-9. 2010
    We studied the relationship between JAK2 (V617F) mutant allele burden and clinical phenotype, disease progression and survival in patients with polycythemia vera (PV)...
  10. 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)...
  11. 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...
  12. 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...
  13. 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...
  14. 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)...
  15. 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...
  16. 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)...
  17. ncbi Two routes to leukemic transformation after a JAK2 mutation-positive myeloproliferative neoplasm
    Philip A Beer
    Department of Haematology, Cambridge Institute for Medical Research, Cambridge, UK
    Blood 115:2891-900. 2010
    Acute myeloid leukemia (AML) may follow a JAK2-positive myeloproliferative neoplasm (MPN), although the mechanisms of disease evolution, often involving loss of mutant JAK2, remain obscure...
  18. 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...
  19. pmc The JAK2 V617F mutation occurs in hematopoietic stem cells in polycythemia vera and predisposes toward erythroid differentiation
    Catriona H M Jamieson
    Department of Medicine and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 103:6224-9. 2006
    ..of patients with polycythemia vera (PV) harbor a valine-to-phenylalanine mutation at amino acid 617 (V617F) in the JAK2 signaling molecule, the stage of hematopoiesis at which the mutation arises is unknown...
  20. ncbi 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)...
  21. 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)...
  22. 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...
  23. 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 ..
  24. 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)...
  25. 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 ..
  26. 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...
  27. 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...
  28. ncbi The structure of the GM-CSF receptor complex reveals a distinct mode of cytokine receptor activation
    Guido Hansen
    Biota Structural Biology Laboratory, St Vincent s Institute of Medical Research, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia
    Cell 134:496-507. 2008
    ..This unusual form of receptor assembly likely applies also to IL-3 and IL-5 receptors, providing a structural basis for understanding their mechanism of activation and for the development of therapeutics...
  29. 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...
  30. 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...
  31. 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...
  32. 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...
  33. 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...
  34. 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)...
  35. 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 ..
  36. 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...
  37. 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...
  38. 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...
  39. doi 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...
  40. 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...
  41. 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...
  42. 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...
  43. 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...
  44. 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...
  45. 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...
  46. ncbi 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...
  47. 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
    ....
  48. 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...
  49. 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...
  50. 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 ..
  51. ncbi Host genetic variation contributes to phenotypic diversity in myeloproliferative disorders
    Animesh Pardanani
    Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
    Blood 111:2785-9. 2008
    ..receptors for erythropoietin (EPOR), thrombopoietin (MPL), and granulocyte colony-stimulating factor (GCSFR), and JAK2. We genotyped 32 linkage disequilibrium tag single nucleotide polymorphism (SNP) loci in 179 white patients: 84 had ..
  52. ncbi The clinical phenotype of wild-type, heterozygous, and homozygous JAK2V617F in polycythemia vera
    Ayalew Tefferi
    Division of Hematology and Laboratory Medicine, Mayo Clinic, Rochester, Minnesota 55905, and Department of Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Cancer 106:631-5. 2006
    Several studies have recently reported on the occurrence of a JAK2(V617F) mutation in myeloid cells from the majority of patients with polycythemia vera (PV). The clinical relevance of this novel observation currently is under study.
  53. 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)...
  54. 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 ..
  55. 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)...
  56. 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...
  57. 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...
  58. 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 ..
  59. 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...
  60. 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...
  61. ncbi Bone marrow JAK2V617F allele burden and clinical correlates in polycythemia vera
    A Tefferi
    Leukemia 21:2074-5. 2007
  62. 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...
  63. 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)...
  64. ncbi Jak2 deficiency defines an essential developmental checkpoint in definitive hematopoiesis
    H Neubauer
    Institute of Medical Microbiology, Immunology, and Hygiene, Technical University of Munich, Germany
    Cell 93:397-409. 1998
    ..A targeted inactivation of Jak2 was performed. Jak2-/- embryos are anemic and die around day 12.5 postcoitum...
  65. 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 ..
  66. ncbi 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...
  67. 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...
  68. 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 ..
  69. 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...
  70. 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...
  71. 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 ..
  72. 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)...
  73. ncbi JAK2 V617F is specifically associated with idiopathic splanchnic vein thrombosis
    S Regina
    J Thromb Haemost 5:859-61. 2007
  74. 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...
  75. ncbi A t(8;9) translocation with PCM1-JAK2 fusion in a patient with T-cell lymphoma
    J Adelaide
    Leukemia 20:536-7. 2006
  76. 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)...
  77. 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...
  78. 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 ..
  79. 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
  80. 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...
  81. 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...
  82. 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)...
  83. 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
  84. 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.
  85. 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
  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. 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...
  88. 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 ..
  89. 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...
  90. 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...
  91. 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...
  92. 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...
  93. 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...
  94. 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...
  95. 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)...
  96. ncbi 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...
  97. pmc Activation of Jak2 catalytic activity requires phosphorylation of Y1007 in the kinase activation loop
    J Feng
    Department of Biochemistry, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Mol Cell Biol 17:2497-501. 1997
    ..Within the Jak2 kinase domain, there is a region that has considerable sequence homology to the regulatory region of the insulin ..
  98. 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 ..

Research Grants96

  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. MOLECULAR AND CELLULAR BIOLOGY OF THROMBOPOIETIN
    KENNETH contact KAUSHANSKY; Fiscal Year: 2010
    ..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 ..
  3. Role of JAK2V617F in the Pathogenesis of Myeloproliferative Disorders.
    M Golam Mohi; Fiscal Year: 2010
    ..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 ..
  4. AKT Signaling and Oxidative Stress Regulation of Erythropoiesis
    Saghi Ghaffari; Fiscal Year: 2010
    ..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...
  5. 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 ..
  6. Role of JAK2V617F in the Pathogenesis of Myeloproliferative Disorders.
    M Golam Mohi; Fiscal Year: 2009
    ..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 ..
  7. 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 ..
  8. Role of JAK2V617F in the Pathogenesis of Myeloproliferative Disorders.
    M Golam Mohi; Fiscal Year: 2009
    ..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 ..
  9. MOLECULAR AND CELLULAR BIOLOGY OF THROMBOPOIETIN
    KENNETH contact KAUSHANSKY; Fiscal Year: 2010
    ..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 ..
  10. MOLECULAR AND CELLULAR BIOLOGY OF THROMBOPOIETIN
    KENNETH contact KAUSHANSKY; Fiscal Year: 2011
    ..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 ..
  11. 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 ..
  12. TYROSINE KINASE ONCOGENES IN ACUTE MYELOID LEUKEMIAS
    JAMES DOUGLAS GRIFFIN; Fiscal Year: 2011
    ..propose to initiate specific, focused projects on two other tyrosine kinases mutated in myeloid leukemias, KIT and JAK2. The major focus of the proposal remains on FLT3, The proposed studies are aimed at testing the hypothesis that "..
  13. Tyrosine Kinase JAK2 and Myeloproliferative Disorders
    ZHIZHUANG ZHAO; Fiscal Year: 2009
    ..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 ..
  14. MOLECULAR AND CELLULAR BIOLOGY OF THROMBOPOIETIN
    Kenneth Kaushansky; Fiscal Year: 2009
    ..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 ..
  15. 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...
  16. 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...
  17. Molecular Pathogenesis & Therapy of JAK2 V617F-induced Myeloproliferative Disease
    Richard A Van Etten; Fiscal Year: 2010
    ..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...
  18. 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...
  19. 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...
  20. Animal Models of P. Vera
    Jerry Spivak; Fiscal Year: 2006
    ..Recently, a JAK2 point mutation (V617F) was identified in the majority of PV patients and also in some IM and ET patients...
  21. Animal Models of P. Vera
    Jerry Spivak; Fiscal Year: 2007
    ..Recently, a JAK2 point mutation (V617F) was identified in the majority of PV patients and also in some IM and ET patients...
  22. 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...
  23. Predictors of therapeutic responsiveness to lestaurtinib in myelofibrosis
    Elizabeth O Hexner; Fiscal Year: 2010
    ..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 ..
  24. 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...
  25. STUDIES OF BCR/ABL LEUKEMOGENESIS IN MICE
    Richard A Van Etten; Fiscal Year: 2010
    ..TK, product of the Ph chromosome translocation in chronic myeloid leukemia (CML), and the recently discovered JAK2 V617F mutant, found in most patients with polycythemia vera (PV). Current therapy for these diseases is nadequate...
  26. Role of Gab2 and Shp2 in Hematopoietic Signalling
    BENJAMIN NEEL; Fiscal Year: 2007
    ..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...
  27. Role of Gab2 and Shp2 in Hematopoietic Signalling
    BENJAMIN NEEL; Fiscal Year: 2009
    ..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...
  28. Role of Gab2 and Shp2 in Hematopoietic Signalling
    BENJAMIN NEEL; Fiscal Year: 2006
    ..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...
  29. Predictors of therapeutic responsiveness to lestaurtinib in myelofibrosis
    Elizabeth Hexner; Fiscal Year: 2009
    ..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 ..
  30. AKT Signaling and Oxidative Stress Regulation of Erythropoiesis
    Saghi Ghaffari; Fiscal Year: 2009
    ..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...
  31. Molecular Pathogenesis & Therapy in JAK2 V617F Myeloproliferative Disease
    Virginia Zaleskas; Fiscal Year: 2007
    ..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...
  32. Molecular Pathogenesis & Therapy of JAK2 V617F-induced Myeloproliferative Disease
    RICHARD VAN ETTEN; 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...
  33. Tyrosine Phosphatase PTP-MEG2 and Hematopoiesis
    ZHIZHUANG ZHAO; Fiscal Year: 2006
    ..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...
  34. Tyrosine Phosphatases PTP-MEG2 and Hematopoiesis
    ZHIZHUANG ZHAO; Fiscal Year: 2007
    ..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...
  35. 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...
  36. Genetic Basis of Polycythemia Vera
    Josef Prchal; Fiscal Year: 2007
    ..disomy was reproduced and provided the basis for the recent discovery of the constitutively active mutant JAK2 V617F on chromosome 9p that is present in the majority of PV patients: JAK2 is mutated in a single allele and it is ..
  37. Genetic Basis of Polycythemia Vera
    Josef Prchal; Fiscal Year: 2006
    ..disomy was reproduced and provided the basis for the recent discovery of the constitutively active mutant JAK2 V617F on chromosome 9p that is present in the majority of PV patients: JAK2 is mutated in a single allele and it is ..
  38. CRLF2 signaling in B-cell acute lymphoblastic leukemia
    DAVID MARC WEINSTOCK; Fiscal Year: 2010
    ..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...
  39. STUDIES OF BCR/ABL LEUKEMOGENESIS IN MICE
    RICHARD VAN ETTEN; Fiscal Year: 2007
    ..TK, product of the Ph chromosome translocation in chronic myeloid leukemia (CML), and the recently discovered JAK2 V617F mutant, found in most patients with polycythemia vera (PV). Current therapy for these diseases is nadequate...
  40. STUDIES OF BCR/ABL LEUKEMOGENESIS IN MICE
    RICHARD VAN ETTEN; Fiscal Year: 2006
    ..TK, product of the Ph chromosome translocation in chronic myeloid leukemia (CML), and the recently discovered JAK2 V617F mutant, found in most patients with polycythemia vera (PV). Current therapy for these diseases is nadequate...
  41. STUDIES OF BCR/ABL LEUKEMOGENESIS IN MICE
    RICHARD VAN ETTEN; Fiscal Year: 2009
    ..TK, product of the Ph chromosome translocation in chronic myeloid leukemia (CML), and the recently discovered JAK2 V617F mutant, found in most patients with polycythemia vera (PV). Current therapy for these diseases is nadequate...
  42. 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...
  43. Role of JAK2-PAK1 interaction in prolactin-dependent signaling
    Maria Diakonova; Fiscal Year: 2010
    ..Tyrosine (Tyr) kinase JAK2 was identified as a PRLR-bound signaling molecule...
  44. Growth Hormone Regulation of SH2B1
    Christin Carter Su; Fiscal Year: 2010
    ..SH2B1 is recruited to JAK2 and is a critical component in GH regulation of the actin cytoskeleton, a prerequisite for cellular proliferation, ..
  45. 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, ..
  46. Growth Hormone Regulation of SH2B1
    Christin Carter-Su; Fiscal Year: 2012
    ..SH2B1 is recruited to JAK2 and is a critical component in GH regulation of the actin cytoskeleton, a prerequisite for cellular proliferation, ..
  47. Characterization of a Novel Erythropoietin Signaling Pathway
    Adam N Goldfarb; Fiscal Year: 2011
    ..In addition, the essential EpoR downstream mediators, JAK2 and PLC3, will be analyzed for their contributions to PKD activation...
  48. 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...
  49. Characterization of a Novel Erythropoietin Signaling Pathway
    Adam N Goldfarb; Fiscal Year: 2010
    ..In addition, the essential EpoR downstream mediators, JAK2 and PLC3, will be analyzed for their contributions to PKD activation...
  50. Stem cells in liver regeneration: fusion or plasticity
    Bryon E Petersen; Fiscal Year: 2010
    ..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. Molecular Pathogenesis and Therapy of ET and PMF
    Ross L Levine; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Activating mutations in JAK2 and in MPL are present in the majority of patients with the myeloproliferative neoplasms (MPN) essential thrombocytosis (ET) and primary myelofibrosis (PMF)...
  52. Phosphodiesterase-3B signaling in the Hypothalamus and Obesity
    Abhiram Sahu; Fiscal Year: 2010
    ..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...
  53. Molecular Pathogenesis of MDS and CMML
    Jaroslaw P Maciejewski; Fiscal Year: 2011
    ..In particular areas of somatic UPD have been linked to the presence of biallelic mutations, such as Jak2 (UPD9p) and Ftl3 (UPD13q)...
  54. Molecular Pathogenesis of MDS and CMML
    Jaroslaw P Maciejewski; Fiscal Year: 2010
    ..In particular areas of somatic UPD have been linked to the presence of biallelic mutations, such as Jak2 (UPD9p) and Ftl3 (UPD13q)...
  55. Regulating Hematopoietic Stem Cell Homeostasis through GSK-3
    Wei Tong; Fiscal Year: 2011
    ..including Wnt signaling and cytokines such as Thrombopoietin (Tpo) and Erythropoietin, which signal through JAK2 to activate STAT5, Akt, and MAP kinase pathways...
  56. IL-6-mediated Jak2/Stat3 signaling and Brain Development
    Jun Tan; Fiscal Year: 2010
    ..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 ..
  57. 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...
  58. Growth hormone signaling and lipid metabolism in fatty liver disease
    ETHAN WEISS; Fiscal Year: 2011
    ..How these livers accumulate lipid remains unknown. GH signals through the Janus kinase 2 (JAK2)...
  59. Regulation of Cell Signaling by Human Biliverdin Reductase
    Mahin D Maines; Fiscal Year: 2011
    ..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...
  60. TYROSINE PHOSPHORYLATION AND GROWTH HORMONE SIGNALING
    Stuart J Frank; Fiscal Year: 2010
    ..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...
  61. The Role of Leptin in Liver Fibrogenesis
    Frank A Anania; Fiscal Year: 2010
    ..that adiponectin is protective against leptin-induced hepatic fibrosis in vitro and in vivo by AMPK blockade of Jak2/Stat3 signal transduction. Three specific aims have been designed to test this hypothesis. (1)...
  62. The Role of Leptin in Liver Fibrogenesis
    Frank Anania; Fiscal Year: 2009
    ..that adiponectin is protective against leptin-induced hepatic fibrosis in vitro and in vivo by AMPK blockade of Jak2/Stat3 signal transduction. Three specific aims have been designed to test this hypothesis. (1)...
  63. The Role of Leptin in Liver Fibrogenesis
    Frank Anania; Fiscal Year: 2009
    ..that adiponectin is protective against leptin-induced hepatic fibrosis in vitro and in vivo by AMPK blockade of Jak2/Stat3 signal transduction. Three specific aims have been designed to test this hypothesis. (1)...
  64. Cytokine Signaling in Autoimmune APC Dysfunction
    Sally Litherland; Fiscal Year: 2004
    ..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. 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...
  66. SIGNALING BY THE ERYTHROPOIETIN RECEPTOR
    Harvey Lodish; Fiscal Year: 1999
    ..We showed that at least one protein-tyrosine kinase additional to JAK2 is involved in signaling by the EpoR, and we want to identify this kinase and determine its functions...
  67. SIGNALING BY THE ERYTHROPOIETIN RECEPTOR
    Harvey Lodish; Fiscal Year: 2000
    ..We showed that at least one protein-tyrosine kinase additional to JAK2 is involved in signaling by the EpoR, and we want to identify this kinase and determine its functions...
  68. SRC-LIKE KINASES IN INTERLEUKIN-3 RECEPTOR SIGNALING
    Steven Anderson; Fiscal Year: 2000
    ..It appears that the activation of JAK2 and STAT molecules may be necessary, but not sufficient, for GM-CSF-induced mitogenesis...
  69. 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...
  70. SRC-LIKE KINASES IN INTERLEUKIN-3 RECEPTOR SIGNALING
    Steven Anderson; Fiscal Year: 1999
    ..It appears that the activation of JAK2 and STAT molecules may be necessary, but not sufficient, for GM-CSF-induced mitogenesis...
  71. Growth Hormone Receptor Dimerization/Disulfide Linkage
    STUART FRANK; Fiscal Year: 2001
    ..domain and signals via its cytoplasmic domain's regulated interaction with molecules including the tyrosine kinase, JAK2. GH promotes homodimerization of GHRs such that a 1:2 GH:GHR complex is believed to constitute the activated GHR ..
  72. Regulation of Cell Signaling by Human Biliverdin Reductase
    Mahin D Maines; Fiscal Year: 2011
    ..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...
  73. Growth Hormone Receptor Dimerization/Disulfide Linkage
    STUART FRANK; Fiscal Year: 2005
    ..domain and signals via its cytoplasmic domain's regulated interaction with molecules including the tyrosine kinase, JAK2. GH promotes homodimerization of GHRs such that a 1:2 GH:GHR complex is believed to constitute the activated GHR ..
  74. Growth Hormone Receptor Dimerization/Disulfide Linkage
    STUART FRANK; Fiscal Year: 2002
    ..domain and signals via its cytoplasmic domain's regulated interaction with molecules including the tyrosine kinase, JAK2. GH promotes homodimerization of GHRs such that a 1:2 GH:GHR complex is believed to constitute the activated GHR ..
  75. Growth Hormone Receptor Dimerization/Disulfide Linkage
    STUART FRANK; Fiscal Year: 2003
    ..domain and signals via its cytoplasmic domain's regulated interaction with molecules including the tyrosine kinase, JAK2. GH promotes homodimerization of GHRs such that a 1:2 GH:GHR complex is believed to constitute the activated GHR ..
  76. Growth Hormone Receptor Dimerization/Disulfide Linkage
    STUART FRANK; Fiscal Year: 2004
    ..domain and signals via its cytoplasmic domain's regulated interaction with molecules including the tyrosine kinase, JAK2. GH promotes homodimerization of GHRs such that a 1:2 GH:GHR complex is believed to constitute the activated GHR ..
  77. Targeted Cancer Therapeutics and Heart Failure: Mechanisms and Post-Injury Rep
    Thomas Force; Fiscal Year: 2009
    ..g. lestaurtinib, a JAK2 inhibitor), encouraging them to prospectively examine LV function in late phase clinical trials or early post-FDA ..
  78. Erythropoietin receptor /Janus Kinase 2 complex
    Lily Huang; Fiscal Year: 2003
    ..The EpoR lacks intrinsic catalytic activity and relies on Janus Kinase 2 (JAK2) for signal transduction...
  79. Role of the serine-threonine kinase PAK1 in prolactin-dependent signaling
    Maria Diakonova; Fiscal Year: 2006
    ..Tyrosine (Tyr) kinase JAK2 was identified as a PRLR-bound signaling molecule...
  80. Erythropoietin receptor /Janus Kinase 2 complex
    Lily Huang; Fiscal Year: 2002
    ..The EpoR lacks intrinsic catalytic activity and relies on Janus Kinase 2 (JAK2) for signal transduction...
  81. 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...