Jak3

Summary

Gene Symbol: Jak3
Description: Janus kinase 3
Alias: JAK-3, JAK3_HUMAN, JAKL, L-JAK, LJAK, tyrosine-protein kinase JAK3, Janus kinase 3 (a protein tyrosine kinase, leukocyte), leukocyte Janus kinase
Species: human

Top Publications

  1. pmc Janus kinase 3: the controller and the controlled
    Wei Wu
    Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, Oklahoma City, 73104, USA
    Acta Biochim Biophys Sin (Shanghai) 44:187-96. 2012
  2. ncbi Reconstitution of early lymphoid proliferation and immune function in Jak3-deficient mice by interleukin-3
    M P Brown
    Howard Hughes Medical Institute, Department of Biochemistry, St Jude Children s Research Hospital, Memphis, TN, USA
    Blood 94:1906-14. 1999
  3. doi Recent patents in the discovery of small molecule inhibitors of JAK3
    Lawrence J Wilson
    Emory University, Emory Institute for Drug Discovery, 1521 Dickey Drive, Atlanta, GA 30322, USA
    Expert Opin Ther Pat 20:609-23. 2010
  4. ncbi Unusual clinical and immunologic manifestations of transplacentally acquired maternal T cells in severe combined immunodeficiency
    Kricia Palmer
    Division of Pediatric Allergy and Immunology, Duke University Medical Center, Durham, NC 27710, USA
    J Allergy Clin Immunol 120:423-8. 2007
  5. ncbi Activation of JAK3, but not JAK1, is critical to interleukin-4 (IL4) stimulated proliferation and requires a membrane-proximal region of IL4 receptor alpha
    M G Malabarba
    Biological Carcinogenesis and Development Program, Program Resources Inc DynCorp, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA
    J Biol Chem 270:9630-7. 1995
  6. pmc Janus kinases in immune cell signaling
    Kamran Ghoreschi
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Immunol Rev 228:273-87. 2009
  7. pmc Ligand-independent homomeric and heteromeric complexes between interleukin-2 or -9 receptor subunits and the gamma chain
    Yaniv Malka
    Department of Neurobiology, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel
    J Biol Chem 283:33569-77. 2008
  8. ncbi Unexpected and variable phenotypes in a family with JAK3 deficiency
    D M Frucht
    Arthritis and Rheumatism Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, Bethesda, MD, USA
    Genes Immun 2:422-32. 2001
  9. pmc NSC114792, a novel small molecule identified through structure-based computational database screening, selectively inhibits JAK3
    Byung Hak Kim
    Department of Pediatrics, Division of Hematology Oncology, New York Medical College, Valhalla, New York 10595, USA
    Mol Cancer 9:36. 2010
  10. ncbi Impaired NFAT regulation and its role in a severe combined immunodeficiency
    S Feske
    The Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA
    Immunobiology 202:134-50. 2000

Research Grants

  1. Jennifer M Puck; Fiscal Year: 2014
  2. MECHANISMS OF ALLOGENEIC STEM CELL EDUCATION IN SCID
    Rebecca H Buckley; Fiscal Year: 2010
  3. JULIAN G CAMBRONERO; Fiscal Year: 2016
  4. UTPAL P DAVE; Fiscal Year: 2016
  5. Regulation of IL4 signal transduciton by poly (ADP-ribose) polymerase-1.
    Rahul Datta; Fiscal Year: 2011
  6. Sergei P Atamas; Fiscal Year: 2014
  7. Immunobiology of Jak3 Deficient Mice
    Leslie J Berg; Fiscal Year: 2010
  8. IRS phosphorylation by type I IL-4R signaling and its role in allergic disease
    Nicola M Heller; Fiscal Year: 2010
  9. Richard J Lamont; Fiscal Year: 2016
  10. IRS phosphorylation by type I IL-4R signaling and its role in allergic disease
    Nicola M Heller; Fiscal Year: 2013

Detail Information

Publications274 found, 100 shown here

  1. pmc Janus kinase 3: the controller and the controlled
    Wei Wu
    Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, Oklahoma City, 73104, USA
    Acta Biochim Biophys Sin (Shanghai) 44:187-96. 2012
    ..In particular, JAK3 has unique functions in the lymphoid system such that JAK3 ablation results in phenotypes resembling severe ..
  2. ncbi Reconstitution of early lymphoid proliferation and immune function in Jak3-deficient mice by interleukin-3
    M P Brown
    Howard Hughes Medical Institute, Department of Biochemistry, St Jude Children s Research Hospital, Memphis, TN, USA
    Blood 94:1906-14. 1999
    ..progenitors requires interleukin-7 (IL-7), which functions through gamma(c)-mediated receptor activation of Jak3. Jak3 deficiency is a cause of severe combined immunodeficiency (SCID) in humans and mice...
  3. doi Recent patents in the discovery of small molecule inhibitors of JAK3
    Lawrence J Wilson
    Emory University, Emory Institute for Drug Discovery, 1521 Dickey Drive, Atlanta, GA 30322, USA
    Expert Opin Ther Pat 20:609-23. 2010
    ..Disruption of JAK3 function results in quantitative and qualitative deficiencies in both B- and T-cell compartments of the immune ..
  4. ncbi Unusual clinical and immunologic manifestations of transplacentally acquired maternal T cells in severe combined immunodeficiency
    Kricia Palmer
    Division of Pediatric Allergy and Immunology, Duke University Medical Center, Durham, NC 27710, USA
    J Allergy Clin Immunol 120:423-8. 2007
    ..We present evidence that these cells can cause allograft rejection and immune cytopenias...
  5. ncbi Activation of JAK3, but not JAK1, is critical to interleukin-4 (IL4) stimulated proliferation and requires a membrane-proximal region of IL4 receptor alpha
    M G Malabarba
    Biological Carcinogenesis and Development Program, Program Resources Inc DynCorp, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA
    J Biol Chem 270:9630-7. 1995
    The tyrosine kinases JAK1 and JAK3 have been shown to undergo tyrosine phosphorylation in response to interleukin-2 (IL), IL4, IL7, and IL9, cytokines which share the common IL2 receptor gamma-chain (IL2R gamma), and evidence has been ..
  6. pmc Janus kinases in immune cell signaling
    Kamran Ghoreschi
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Immunol Rev 228:273-87. 2009
    The Janus family kinases (Jaks), Jak1, Jak2, Jak3, and Tyk2, form one subgroup of the non-receptor protein tyrosine kinases...
  7. pmc Ligand-independent homomeric and heteromeric complexes between interleukin-2 or -9 receptor subunits and the gamma chain
    Yaniv Malka
    Department of Neurobiology, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel
    J Biol Chem 283:33569-77. 2008
    ..heteromeric interactions between specific interleukin receptor subunits, which bind Janus kinase 1 (JAK1) and the JAK3 binding common gamma chain (gamma c)...
  8. ncbi Unexpected and variable phenotypes in a family with JAK3 deficiency
    D M Frucht
    Arthritis and Rheumatism Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, Bethesda, MD, USA
    Genes Immun 2:422-32. 2001
    Mutations of the Janus kinase 3 (JAK3) have been previously described to cause an autosomal recessive variant of severe combined immunodeficiency (SCID) usually characterized by the near absence of T and NK cells, but preserved numbers of ..
  9. pmc NSC114792, a novel small molecule identified through structure-based computational database screening, selectively inhibits JAK3
    Byung Hak Kim
    Department of Pediatrics, Division of Hematology Oncology, New York Medical College, Valhalla, New York 10595, USA
    Mol Cancer 9:36. 2010
    Human or animals lacking either JAK3 or the common gamma chain (gammac) expression display severe combined immunodeficiency disease, indicating the crucial role of JAK3 in T-cell development and the homeostasis of the immune system...
  10. ncbi Impaired NFAT regulation and its role in a severe combined immunodeficiency
    S Feske
    The Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA
    Immunobiology 202:134-50. 2000
    ....
  11. ncbi Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution
    Rebecca H Buckley
    Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA
    Annu Rev Immunol 22:625-55. 2004
    ..The products of three of the genes--IL-2RG, Jak3, and IL-7R alpha--are components of cytokine receptors, and the products of three more-RAG1, RAG2, and Artemis-are ..
  12. doi Mutations causing severe combined immunodeficiency: detection with a custom resequencing microarray
    Tonya Lebet
    Department of Pediatrics, University of California San Francisco School of Medicine, San Francisco, California 94143 0519, USA
    Genet Med 10:575-85. 2008
    ..A resequencing microarray could facilitate mutation detection, increasing the chance of diagnosing infants early for optimal rescue by hematopoietic stem cell transplantation...
  13. pmc Specificities of CD40 signaling: involvement of TRAF2 in CD40-induced NF-kappaB activation and intercellular adhesion molecule-1 up-regulation
    H H Lee
    Department of Microbiology and Molecular Genetics, Jonsson Comprehensive Cancer Center, Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA
    Proc Natl Acad Sci U S A 96:1421-6. 1999
    ..factor receptor-associated factor (TRAF) family proteins including TRAF2, TRAF3, TRAF5, and TRAF6, as well as Jak3, have been implicated as potential mediators of CD40 signaling...
  14. ncbi Regulation of IGF-I mRNA and signal transducers and activators of transcription-3 and -5 (Stat-3 and -5) by GH in C2C12 myoblasts
    Robert A Frost
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Endocrinology 143:492-503. 2002
    ..Our data suggest that Janus kinases (Jak2 or Jak3) and their downstream targets (Stat3 and Stat5) may play important roles in the expression of IGF-I mRNA and the ..
  15. ncbi Aberrant expression of interleukin-7 (IL-7) and its signalling complex in human breast cancer
    M A A Al-Rawi
    Metastasis Research Group, University Department of Surgery, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, Wales, UK
    Eur J Cancer 40:494-502. 2004
    ..Measuring these molecules in breast cancer tissues may provide, for the first time, important molecular indicators of tumour differentiation, aggressiveness, nodal status, prognosis and patient survival...
  16. doi Molecular signatures distinguishing active from latent tuberculosis in peripheral blood mononuclear cells, after in vitro antigenic stimulation with purified protein derivative of tuberculin (PPD) or Candida: a preliminary report
    Joel N H Stern
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Immunol Res 45:1-12. 2009
    ..in ATBI patients, the following genes were found to be up-regulated and absent in LTBI individuals: two kinases (JAK3 and p38MAPK), four interleukins (IL-7, IL-2, IL-6, and IFNbeta1), a chemokine (HCC-4) a chemokine receptor (CxCR5), ..
  17. ncbi Mechanism of inflammation in murine eosinophilic myocarditis produced by adoptive transfer with ovalbumin challenge
    Masao Hirasawa
    Department of Anatomy and Biology, Osaka Medical College, Osaka, Japan
    Int Arch Allergy Immunol 142:28-39. 2007
    ..We investigated the relationships between these cytokines and receptors in the development of inflammation in murine myocarditis produced by adoptive transfer, with reference to eosinophil infiltration and signal transduction...
  18. pmc Direct interaction between Kit and the interleukin-7 receptor
    Thomas Jahn
    Division of Research Immunology and Bone Marrow Transplantation, Childrens Hospital Los Angeles, CA, USA
    Blood 110:1840-7. 2007
    ..a complex with either IL-7Ralpha or gammac, and tyrosine phosphorylation of both subunits occurred independently of Jak3, suggesting that gammac and IL-7Ralpha are each direct substrates of Kit...
  19. pmc New concepts in phospholipase D signaling in inflammation and cancer
    Julian Gomez-Cambronero
    Department of Biochemistry and Molecular Biology, Wright State University School Medicine, Dayton, OH, USA
    ScientificWorldJournal 10:1356-69. 2010
    ..They are Y296, Y415, and Y511 and the responsible kinases are, respectively, EGFR, JAK3, and Src...
  20. ncbi Signalling by cytokines interacting with the interleukin-2 receptor gamma chain
    J B Demoulin
    Ludwig Institute for Cancer Research, Brussels, Belgium
    Cytokines Cell Mol Ther 4:243-56. 1998
    ..Gammac is physically and functionally associated with the JAK3 tyrosine kinase...
  21. ncbi Transcription factor STAT5A is a substrate of Bruton's tyrosine kinase in B cells
    S Mahajan
    Molecular Signal Transduction Laboratory, Parker Hughes Cancer Center and the Department of Biochemistry, Parker Hughes Institute, St Paul, Minnesota 55113, USA
    J Biol Chem 276:31216-28. 2001
    ..of STAT5 protein was prevented by pretreatment with the BTK inhibitor LFM-A13 but not by pretreatment with the JAK3 inhibitor HI-P131...
  22. ncbi Partial restoration of B cell development in Jak-3(-/-) mice achieved by co-expression of IgH and E(mu)-myc transgenes
    Stacey R Dillon
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Int Immunol 14:893-904. 2002
    ..Thus, Jak-3 seems to play several important roles in B cells: during development, to enable cell division, Ig gene rearrangement and cell differentiation, and in mature cells, to promote B cell survival in the periphery...
  23. pmc Potent activity of a nucleoside reverse transcriptase inhibitor, 4'-ethynyl-2-fluoro-2'-deoxyadenosine, against human immunodeficiency virus type 1 infection in a model using human peripheral blood mononuclear cell-transplanted NOD/SCID Janus kinase 3 kno
    Shinichiro Hattori
    Division of Hematopoiesis, Center for AIDS Research, Kumamoto University Graduate School of Medical and Pharmaceutical Sciences, Kumamoto, Japan
    Antimicrob Agents Chemother 53:3887-93. 2009
    ..These data suggest that EFdA is a promising candidate for a new age of HIV-1 chemotherapy and should be developed further as a potential therapy for individuals with multidrug-resistant HIV-1 variants...
  24. ncbi T cell development and activation in Jak3-deficient mice
    A M Baird
    Department of Pathology, University of Massachusetts Medical Center, Worcester 01655, USA
    J Leukoc Biol 63:669-77. 1998
    b>Jak3, a member of the Janus family of tyrosine kinases, participates in signaling through cytokine receptors that contain the common gamma-chain, including the receptors for interleukin (IL)-2, IL-4, IL-7, IL-9, and IL-15...
  25. ncbi Dysregulated myelopoiesis in mice lacking Jak3
    W J Grossman
    Divisions of Molecular Microbiology and Cardiology, Departments of Pathology and Medicine, Washington University School of Medicine, St Louis, MO, USA
    Blood 94:932-9. 1999
    b>Jak3 is a cytoplasmic tyrosine kinase that associates with the common chain of the interleukin-2 (IL-2) receptor and is involved in the function of the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15...
  26. ncbi Growth hormone receptor interaction with Jak proteins differs between tissues
    G Hellgren
    Research Centre for Endocrinology and Metabolism, Department of Internal Medicine, Sahlgrenska University Hospital, Goteborg, Sweden
    J Interferon Cytokine Res 21:75-83. 2001
    ..The specificity of the four members of the Jak family (Jak1, Jak2, Jak3, and Tyk2) for different cytokine receptors is not fully understood...
  27. ncbi Interleukin 7 induces the growth of breast cancer cells through a wortmannin-sensitive pathway
    M A A Al-Rawi
    Metastasis Research Group, University Department of Surgery, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK
    Br J Surg 91:61-8. 2004
    ..Its effects on solid tumours, including breast cancer, are unknown. This report concerns the effect of IL-7 on the growth of breast cancer cells...
  28. pmc BLNK suppresses pre-B-cell leukemogenesis through inhibition of JAK3
    Joji Nakayama
    Division of Molecular Biology, Research Institute for Biological Sciences, Tokyo University of Science, Noda, Japan
    Blood 113:1483-92. 2009
    ..Here, we demonstrate that the JAK3/STAT5 signaling pathway is constitutively activated in pre-B leukemia cells derived from BLNK(-/-) mice, mostly due ..
  29. pmc Tumor-shed PGE(2) impairs IL2Rgammac-signaling to inhibit CD4 T cell survival: regulation by theaflavins
    Sreya Chattopadhyay
    Division of Molecular Medicine, Bose Institute, P 1 12 CIT Scheme VIIM, Kolkata, India
    PLoS ONE 4:e7382. 2009
    ....
  30. pmc Immunolocalisation of the janus kinases (JAK)--signal transducers and activators of transcription (STAT) pathway in human epidermis
    H Nishio
    Osaka Medical College, Department of Legal Medicine, Takatsuki, Japan
    J Anat 198:581-9. 2001
    ..JAK2, JAK3, STAT1 and STAT5 were expressed in high amounts, and JAK1, TYK2, STAT2, STAT3, STAT4 and STAT6 to a much lesser ..
  31. ncbi The common gamma chain (gamma c) is a required signaling component of the IL-21 receptor and supports IL-21-induced cell proliferation via JAK3
    Tania Habib
    Division of Hematology, University of Washington School of Medicine, Seattle, Washington 98195, USA
    Biochemistry 41:8725-31. 2002
    ..we demonstrate a functional requirement for both gamma c and the gamma c-associated Janus family tyrosine kinase 3 (JAK3) in IL-21-induced proliferation of pro-B-lymphoid cells engineered to express human IL-21R alpha (BaF3/IL-21R alpha)..
  32. ncbi Induction of 15-lipoxygenase expression by IL-13 requires tyrosine phosphorylation of Jak2 and Tyk2 in human monocytes
    B Roy
    Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 273:32023-9. 1998
    ..blotting experiments, IL-13 was shown to induce tyrosine phosphorylation of Jak2 and Tyk2, but not Jak1 or Jak3, within 5 min of treatment in human monocytes...
  33. ncbi Characterization of the cytoplasmic domain of interleukin-13 receptor-alpha
    P L Orchansky
    The Biomedical Research Centre, The University of British Columbia, Vancouver V6T 1Z3, British Columbia, Canada
    J Biol Chem 274:20818-25. 1999
    ..fusion protein of the cytoplasmic domain of IL-13Ralpha was phosphorylated on tyrosine in vitro by JAK1, JAK3, and Tyk2, although the tyrosine phosphorylation events mediated by Tyk2 and JAK3 were not detectable using anti-..
  34. ncbi Functional involvement of Akt signaling downstream of Jak1 in v-Abl-induced activation of hematopoietic cells
    Shinji Oki
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032 3702, USA
    Blood 100:966-73. 2002
    ..The nonreceptor tyrosine kinases Jak1 and Jak3, which bind to the v-Abl oncoprotein, are constitutively activated in cells transformed with the Abelson murine ..
  35. ncbi Immunotherapy for De Novo renal transplantation: what's in the pipeline?
    Helio Tedesco Silva
    Division of Nephrology, Hospital do Rim e Hipertensao, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
    Drugs 66:1665-84. 2006
    ..The most frequent adverse effects have been related to nonspecific binding to JAK2 kinases. CP-690550, a JAK3 inhibitor is currently in phase II clinical trials...
  36. doi Role of Janus kinase-2 in IgE receptor-mediated leukotriene C4 production by mast cells
    Runa Sur
    Johnson and Johnson Consumer and Personal Products Worldwide, Skillman, NJ 19477 0776, USA
    Biochem Biophys Res Commun 390:786-90. 2009
    ..Taken together, these data suggest that JAK2 is a critical regulator of IgE/antigen-induced production of LTC(4) in mast cells...
  37. ncbi Janus kinase 3 (Jak3) is essential for common cytokine receptor gamma chain (gamma(c))-dependent signaling: comparative analysis of gamma(c), Jak3, and gamma(c) and Jak3 double-deficient mice
    K Suzuki
    Department of Internal Medicine II, Chiba University School of Medicine, Chiba 260 8670, Japan
    Int Immunol 12:123-32. 2000
    ..The Janus family tyrosine kinase 3 (Jak3) is known to be associated with gamma(c), and the reported phenotypes of gamma(c)-deficient (gamma(c)(-)) and Jak3-..
  38. ncbi Functional uncoupling of the Janus kinase 3-Stat5 pathway in malignant growth of human T cell leukemia virus type 1-transformed human T cells
    R A Kirken
    Department of Integrative Biology and Pharmacology, University of Texas Health Science Center, Houston, TX 77030, USA
    J Immunol 165:5097-104. 2000
    ..human T cell lines and lymphocytes isolated from HTLV-1-infected patients; therefore, a critical role for the Jak3-Stat5 pathway in the progression of this disease has been postulated...
  39. ncbi Developmental defects of lymphoid cells in Jak3 kinase-deficient mice
    S Y Park
    Division of Molecular Genetics, Chiba University School of Medicine, Japan
    Immunity 3:771-82. 1995
    b>Jak3 is a tyrosine kinase mediating cytokine receptor signaling through the association with the common gamma chain of the cytokine receptors such as IL-2, IL-4, IL-7, IL-9, and IL-15...
  40. ncbi Thrombin induces expression of cytokine-induced SH2 protein (CIS) in rat brain astrocytes: involvement of phospholipase A2, cyclooxygenase, and lipoxygenase
    Kyung Ae Ji
    Neuroscience Graduate Program, Brain Disease Research Center, Ajou University School of Medicine, Suwon, Korea
    Glia 48:102-11. 2004
    ..STAT5 is known to regulate CIS expression, thrombin did not activate STAT5, and inhibitors of JAK2 (AG490) and JAK3 (WHI-P97 and WHI-P154) had little effect on thrombin-induced CIS expression...
  41. ncbi Immunosuppression by the JAK3 inhibitor CP-690,550 delays rejection and significantly prolongs kidney allograft survival in nonhuman primates
    Dominic C Borie
    Transplantation Immunology Laboratory, Department of Cardiothoracic Surgery, Falk Cardiovascular Research Center, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA
    Transplantation 79:791-801. 2005
    Janus kinase 3 (JAK3) mediates signal transduction from cytokine receptors using the common chain (gammac)...
  42. ncbi [Influence of moxibustion on JAK-STAT signal transduction pathways of synovial cells in rheumatoid arthritis rabbits]
    Xin Yang
    Chengdu University of Chinese Medicine, Chengdu 610075, China
    Zhen Ci Yan Jiu 32:75-82. 2007
    ....
  43. ncbi The interleukin-4 receptor activates STAT5 by a mechanism that relies upon common gamma-chain
    A Lischke
    Theodor Boveri Institut für Biowissenschaften Biozentrum, Physiologische Chemie II, Am Hubland, D 97074 Wurzburg, Germany
    J Biol Chem 273:31222-9. 1998
    Interleukin (IL)-4 signaling proceeds via cytoplasmic activation of the Janus kinases JAK1 and JAK3 and the signal transducer and activator of transcription STAT6...
  44. ncbi New strategies for immunosuppression: interfering with cytokines by targeting the Jak/Stat pathway
    JOHN J O'SHEA
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892 1820, USA
    Curr Opin Rheumatol 17:305-11. 2005
    ..This review will discuss strategies to develop novel immunosuppressants that arise from advances in the understanding of cytokine signaling...
  45. doi Phase 1 dose-escalation study of CP-690 550 in stable renal allograft recipients: preliminary findings of safety, tolerability, effects on lymphocyte subsets and pharmacokinetics
    E van Gurp
    Department of Internal Medicine, Section of Nephrology and Transplant, Erasmus Medical Center, Rotterdam, The Netherlands
    Am J Transplant 8:1711-8. 2008
    ..Additional dose-ranging studies are warranted to evaluate the safety and efficacy of CP-690 550 in renal transplant recipients over longer treatment duration...
  46. pmc Acute lymphoblastic leukemia-associated JAK1 mutants activate the Janus kinase/STAT pathway via interleukin-9 receptor alpha homodimers
    Tekla Hornakova
    Ludwig Institute for Cancer Research, Brussels Branch and de Duve Institute, Universite Catholique de Louvain, B 1200 Brussels, Belgium
    J Biol Chem 284:6773-81. 2009
    ..cells alone or together with the other components of the interleukin-9 receptor complex (IL-9Ralpha, gammac, and JAK3)...
  47. doi Downregulation of Janus kinase 3 expression by small interfering RNA in rat composite tissue allotransplantation
    Kao Ping Chang
    Faculty of Medicine, Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
    Transpl Immunol 21:27-32. 2009
    ..The Janus kinase 3 (JAK3) is also pertinent to the development of a new immuno-suppressant...
  48. doi Prevention of UVB-induced skin inflammation, genotoxicity, and photocarcinogenesis in mice by WHI-P131, a dual-function inhibitor of Janus kinase 3 and EGF receptor kinase
    Fatih M Uckun
    Developmental Therapeutics Program, Institute for Pediatric Clinical Research, Childrens Hospital Los Angeles, CA, USA
    Arzneimittelforschung 60:218-25. 2010
    The current study examined the chemopreventive potential of the dual-function JAK3/EGFR tyrosine kinase inhibitor WHI-P131 (CAS 202475-60-3) in photocarcinogenesis of non-melanoma skin cancer (NMSC)...
  49. pmc Constitutive activation of a slowly migrating isoform of Stat3 in mycosis fungoides: tyrphostin AG490 inhibits Stat3 activation and growth of mycosis fungoides tumor cell lines
    M Nielsen
    Institute of Medical Microbiology and Immunology, Section A, University of Copenhagen, 2200 N Copenhagen, Denmark
    Proc Natl Acad Sci U S A 94:6764-9. 1997
    ..showed constitutive DNA-binding properties of Stat3(sm); and (iii) Stat3(sm) was constitutively associated with Jak3. The abnormal activation of Stat3(sm) was highly specific...
  50. ncbi The immunosuppressive metabolite of leflunomide, A77 1726, affects murine T cells through two biochemical mechanisms
    R T Elder
    Department of General Surgery, Rush Presbyterian St Luke s Medical Center, Chicago, IL 60612, USA
    J Immunol 159:22-7. 1997
    ..kinases, since these higher concentrations of A77 1726 inhibit IL-2-induced tyrosine phosphorylation of Jak1 and Jak3, the protein tyrosine kinases initiating signaling by the IL-2R...
  51. ncbi Molecular cloning of a chicken JAK homolog from activated T cells
    L Sofer
    University of Delaware, Department of Animal, Food Sciences, Department of Chemistry, Biochemistry, Newark, DE 19717, USA
    Gene 215:29-36. 1998
    ..The sequence analysis and pattern of expression suggests that this is an avian homolog of JAK3.
  52. ncbi Effects of Th2 cytokines on chemokine expression in the lung: IL-13 potently induces eotaxin expression by airway epithelial cells
    L Li
    Department of Immunology IMM 25, Scripps Research Institute, La Jolla, CA 92037, USA
    J Immunol 162:2477-87. 1999
    ..IL-13 was able to induce eotaxin in the lung of JAK3-deficient mice, suggesting that JAK3 is not required for IL-13 signaling in airway epithelial cells; however, ..
  53. ncbi Altered natural killer cell differentiation in CD34+ progenitors from chronic myeloid leukemia patients
    G Carayol
    INSERM U487, Institut Gustave Roussy, 39, rue Camille Desmoulins, 94805 Villejuif, France
    Oncogene 19:2758-66. 2000
    ..We also demonstrated that in both normal and leukemic progenitors, the signaling kinase Jak3 is constitutively pre-associated with the gammac chain...
  54. ncbi Advances in the understanding and treatment of human severe combined immunodeficiency
    R H Buckley
    Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA
    Immunol Res 22:237-51. 2000
    ..5 mo of life, making early diagnosis crucial. Recently, gene therapy has also been successful in infants with X-linked SCID...
  55. ncbi A newly identified AMSH-family protein is specifically expressed in haploid stages of testicular germ cells
    Keiko Kitajima
    Division of Molecular Regenerative Medicine, Course of Advanced Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
    Biochem Biophys Res Commun 309:135-42. 2003
    ..STAM (AMSH) plays a critical role in the cytokine-mediated intracellular signal transduction downstream of the Jak2/Jak3-STAM complex. We newly identified a family molecule of AMSH, AMSH-FP (AMSH-Family Protein) in the mouse brain...
  56. pmc Inhibition of the antigen-induced activation of rodent mast cells by putative Janus kinase 3 inhibitors WHI-P131 and WHI-P154 in a Janus kinase 3-independent manner
    Watchara Linwong
    Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6 3 Aoba Aramaki, Aoba ku, Sendai, Miyagi 980 8578, Japan
    Br J Pharmacol 145:818-28. 2005
    We analyzed the effects of the Janus kinase 3 (Jak3)-specific inhibitor WHI-P131 (4-(4'-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline) and the Jak3/Syk inhibitor WHI-P154 (4-(3'-bromo-4'-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline) on ..
  57. ncbi JAK-STAT signaling pathway in pulmonary arterial smooth muscle cells is activated by hypoxia
    Guan Song Wang
    Institute of Respiratory Diseases, Xinqiao Hospital, 2 Xinqioa Street, Chongqing 400037, China
    Cell Biol Int 29:598-603. 2005
    ..The expression of JAK1, JAK2, JAK3 and TYK2 mRNA was analyzed by reverse transcription-polymerase chain reaction (RT-PCR)...
  58. ncbi Development of pyrimidine-based inhibitors of Janus tyrosine kinase 3
    Jack J Chen
    Procter and Gamble Pharmaceuticals, Health Care Research Center, 8700 Mason Montgomery Rd, Mason, OH 45040, USA
    Bioorg Med Chem Lett 16:5633-8. 2006
    A new class of pyrimidine-based Janus tyrosine kinase 3 (JAK3) inhibitors are described. Many of these inhibitors showed low nanomolar activity against JAK3.
  59. ncbi Stat5 is essential for early B cell development but not for B cell maturation and function
    Xuezhi Dai
    State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, People s Republic of China
    J Immunol 179:1068-79. 2007
    ..progenitors and myeloid cells but not B cells beyond pro-B cell progenitors in lethally irradiated wild-type or Jak3(-/-) mice. Deletion of Stat5A/5B in vitro directly impaired IL-7-mediated B cell expansion...
  60. doi Receptor expression is essential for proliferation induced by dimerized Jak kinases
    Hodaka Fujii
    Department of Pathology, New York University School of Medicine, 550 First Avenue, MSB 126, New York, NY 10016, USA
    Biochem Biophys Res Commun 370:557-60. 2008
    Two members of Jak kinases, Jak1 and Jak3, are associated with the cytoplasmic domains of the interleukin-2 (IL-2) receptor (IL-2R) beta chain (IL-2Rbeta) and the common cytokine receptor gamma chain (gammac), respectively, and ..
  61. pmc Permission to proceed: Jak3 and STAT5 signaling molecules give the green light for T helper 1 cell differentiation
    Kenneth M Murphy
    Howard Hughes Medical Institute and Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Immunity 28:725-7. 2008
    In this issue of Immunity, Shi et al. (2008) identify a previously unknown requirement in T helper cell differentiation, showing that Jak3 and STAT5 are needed to generate chromatin that is permissive to the activating effects of T-bet.
  62. doi Multiple Gi proteins participate in nerve growth factor-induced activation of c-Jun N-terminal kinases in PC12 cells
    Prudence H Tso
    Department of Biochemistry, the Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China
    Neurochem Res 34:1101-12. 2009
    ..NGF-elevated JNK activity was abolished by inhibitors of JNK, p38 MAPK, Src, JAK3 and MEK1/2...
  63. pmc Janus kinase-3 dependent inflammatory responses in allergic asthma
    Rama Malaviya
    Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA
    Int Immunopharmacol 10:829-36. 2010
    ..We propose that targeting JAK-3 is a rationale approach to control the inflammatory responses of multiple cell types responsible for the pathogenesis of allergic asthma...
  64. pmc IL-8-induced neutrophil chemotaxis is mediated by Janus kinase 3 (JAK3)
    Karen M Henkels
    Department of Biochemistry and Molecular Biology, Wright State University School Medicine, Dayton, OH 45435, USA
    FEBS Lett 585:159-66. 2011
    Janus kinase 3 (JAK3) is a non-receptor tyrosine kinase vital to the regulation of T-cells. We report that JAK3 is a mediator of interleukin-8 (IL-8) stimulation of a different class of hematopoietic relevant cells: human neutrophils...
  65. doi JAK-mutant myeloproliferative neoplasms
    Ross L Levine
    Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Curr Top Microbiol Immunol 355:119-33. 2012
    Although the Janus family of kinases (JAK1, JAK2, JAK3, and TYK2) has been extensively characterized and investigated, the role of Janus kinase activation in the pathogenesis and therapy of human malignancies was not fully appreciated ..
  66. pmc Inhibitory effects of the JAK inhibitor CP690,550 on human CD4(+) T lymphocyte cytokine production
    Kiyoshi Migita
    Department of Rheumatology and Clinical Research Center, NHO Nagasaki Medical Center, Kubara 2 1001 1, Omura 856 8652, Japan
    BMC Immunol 12:51. 2011
    The new JAK3 inhibitor, CP690,550, has shown efficacy in the treatment of rheumatoid arthritis. The present study was undertaken to assess the effects of CP690,550 on cytokine production and cellular signaling in human CD4(+) T cells.
  67. doi RGS2 is a negative regulator of STAT3-mediated Nox1 expression
    Hyung Kyoung Lee
    Department of Biochemistry and Molecular Biology, Aging Associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Nam Gu, Daegu, South Korea
    Cell Signal 24:803-9. 2012
    ..3 (STAT3) to activate Nox1's transcription, as well as cooperative regulation by janus kinase 1 and 3 (JAK1 and JAK3)...
  68. pmc Protection of porcine endothelial cells against apoptosis with interleukin-4
    Sylvester M Black
    Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA
    Xenotransplantation 18:343-54. 2011
    ..Now we define signaling processes activated by IL-4 in porcine ECs and mechanisms required for IL-4-induced protection against apoptosis...
  69. doi JAK3, STAT3 and CD3-zeta signaling proteins status in regard to the lymphocytes function in patients with ovarian cancer
    Magdalena Klink
    Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland
    Immunol Invest 41:382-98. 2012
    ..blood lymphocytes (PBLs) from ovarian cancer patients could be associated with signaling elements such as JAK3, STAT3 and CD3-zeta chain...
  70. pmc The genetic basis of early T-cell precursor acute lymphoblastic leukaemia
    Jinghui Zhang
    Department of Computational Biology and Bioinformatics, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Nature 481:157-63. 2012
    ..mutations in genes regulating cytokine receptor and RAS signalling (67% of cases; NRAS, KRAS, FLT3, IL7R, JAK3, JAK1, SH2B3 and BRAF), inactivating lesions disrupting haematopoietic development (58%; GATA3, ETV6, RUNX1, IKZF1 ..
  71. pmc An N-ethyl-N-nitrosourea (ENU)-induced dominant negative mutation in the JAK3 kinase protects against cerebral malaria
    Silayuv E Bongfen
    Department of Biochemistry, McGill University, Montreal, Canada
    PLoS ONE 7:e31012. 2012
    ..genome sequencing as homozygosity for a mis-sense mutation (W81R) in the FERM domain of Janus-associated kinase 3 (Jak3)...
  72. ncbi Cucurbitacins as inducers of cell death and a rich source of potential anticancer compounds
    J L Rios
    Departament de Farmacologia, Facultat de Farmacia, Universitat de València Av Vicent Andrés Estellés S N, 46100 Burjassot, Valencia, Spain
    Curr Pharm Des 18:1663-76. 2012
    ..for cancer cell proliferation and survival), PARP cleavage, expression of active caspase-3, decreased pSTAT3 and JAK3 levels, as well as decreases in various downstream STAT3 targets such as Mcl-1, Bcl-2, Bcl-xL, and cyclin D3, all ..
  73. pmc Effective elicitation of human effector CD8+ T Cells in HLA-B*51:01 transgenic humanized mice after infection with HIV-1
    Yoshinori Sato
    Center for AIDS Research, Kumamoto University, 2 2 1 Honjo, Kumamoto, Japan
    PLoS ONE 7:e42776. 2012
    ..HLA-B*51:01 transgenic humanized mice by transplanting human CD34(+) HSCs into HLA-B*51:01 transgenic NOD/SCID/Jak3(-/-) mice (hNOK/B51Tg mice) and investigated whether human effector CD8(+) T cells would be elicited in the mice or ..
  74. doi Biologics and other novel approaches as new therapeutic options in myasthenia gravis: a view to the future
    Marinos C Dalakas
    Thomas Jefferson University, Philadelphia, Pennsylvania, USA
    Ann N Y Acad Sci 1274:1-8. 2012
    ..4) cytokines and cytokine receptors targeting interleukin (IL)-6, IL-17, and the Janus tyrosine kinases (JAK)1 and JAK3; and (5) cellular adhesion and T cell migration molecules. Reengineering of pathogenic antibodies (i.e...
  75. ncbi Review: new anti-cytokines for IBD: what is in the pipeline?
    Michael Scharl
    Division of Gastroenterology and Hepatology, Department of Internal Medicine, University Hospital of Zurich, Ramistrasse 100, CH 8091 Zurich, Switzerland
    Curr Drug Targets 14:1405-20. 2013
    ..Taken together a large number of new therapeutic anti-cytokine approaches are currently tested in clinical trials in IBD patients. In this review, the new therapeutic approaches for cytokine inhibition in IBD patients are discussed. ..
  76. pmc Inhibition of IL-6 family cytokines by SOCS3
    Jeffrey J Babon
    Walter and Eliza Hall Institute, Parkville, Australia The University of Melbourne, Parkville, Australia Electronic address
    Semin Immunol 26:13-9. 2014
    ..studies have shown SOCS3 binds to only these three JAKs, all of which are associated with IL-6 signalling, and not JAK3. This specificity is determined by a three residue "GQM" motif in the kinase domain of JAK1, JAK2 and TYK2...
  77. pmc FRA2 is a STAT5 target gene regulated by IL-2 in human CD4 T cells
    Aradhana Rani
    Division of Transplantation Immunology and Mucosal Biology, King s College London, London, United Kingdom
    PLoS ONE 9:e90370. 2014
    ..Furthermore, addition of JAK3 inhibitor (R333) or Daclizumab inhibited the induction in TCR stimulated cells...
  78. doi Downregulation of chloride channel ClC-2 by Janus kinase 3
    Jamshed Warsi
    Department of Physiology I, University of Tubingen, Gmelinstr 5, 72076, Tubingen, Germany
    J Membr Biol 247:387-93. 2014
    Janus kinase-3 (JAK3) fosters proliferation and counteracts apoptosis of lymphocytes and tumor cells. The gain of function mutation (A572V)JAK3 has been discovered in acute megakaryoplastic leukemia...
  79. pmc Adapter protein Shc regulates Janus kinase 3 phosphorylation
    Jayshree Mishra
    From the Department of Pharmaceutical Sciences, Irma Lerma Rangel ILR College of Pharmacy Texas A and M Health Science Center, Kingsville, Texas 78363
    J Biol Chem 289:15951-6. 2014
    Although constitutive activation of Janus kinase 3 (Jak3) leads to different cancers, the mechanism of trans-molecular regulation of Jak3 activation is not known...
  80. doi ATP-mediated kinome selectivity: the missing link in understanding the contribution of individual JAK Kinase isoforms to cellular signaling
    Atli Thorarensen
    Pfizer Worldwide Research, 200 CambridgePark Drive, Cambridge, Massachusetts 02140, United States
    ACS Chem Biol 9:1552-8. 2014
    ..to a recent study, we demonstrate that for IL-15 cytokine signaling it is sufficient to inhibit either JAK1 or JAK3 to fully inhibit downstream STAT5 phosphorylation...
  81. pmc WHI-P154 enhances the chemotherapeutic effect of anticancer agents in ABCG2-overexpressing cells
    Hui Zhang
    Sun Yat sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St John s University, Queens, New York, USA
    Cancer Sci 105:1071-8. 2014
    ..Collectively, these findings highlighted WHI-P154 could significantly reverse ABCG2-mediated multidrug drug resistance by directly blocking the efflux function...
  82. doi Novel hinge-binding motifs for Janus kinase 3 inhibitors: a comprehensive structure-activity relationship study on tofacitinib bioisosteres
    Matthias Gehringer
    Institute of Pharmaceutical Sciences, Department of Pharmaceutical and Medicinal Chemistry, Eberhard Karls University of Tuebingen, Auf der Morgenstelle 8, 72076 Tuebingen Germany, Fax 49 7071 29 5037
    ChemMedChem 9:2516-27. 2014
    ..In the current study, a library of tofacitinib bioisosteres was prepared and tested against JAK3. The compounds possessed the tofacitinib piperidinyl side chain, whereas the hinge binding motif was replaced by a ..
  83. doi Vanadium pentoxide prevents NK-92MI cell proliferation and IFNγ secretion through sustained JAK3 phosphorylation
    Francisco Gallardo-Vera
    a Laboratorio Inmunobiología, Departamento de Biologia Celular y Tisular, Facultad de Medicina
    J Immunotoxicol 13:27-37. 2016
    ..Expression of CD45, SOCS1, JAK3, pJAK3, STAT5, pSTAT5, IL-2R, IL-15R, Fas, and FasL in/on the cells was determined by flow cytometry; JAK3 and ..
  84. doi Piperine blocks interleukin-2-driven cell cycle progression in CTLL-2 T lymphocytes by inhibiting multiple signal transduction pathways
    Carolyn D Doucette
    Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada
    Toxicol Lett 234:1-12. 2015
    ..of transcription (STAT) 3 and STAT5 without affecting the upstream phosphorylation of Janus kinase (JAK) 1 and JAK3. In addition, piperine inhibited the IL-2-induced phosphorylation of extracellular signal-regulated kinase 1/2 and ..
  85. pmc Long-term Benefit of PD-L1 Blockade in Lung Cancer Associated with JAK3 Activation
    Eliezer M Van Allen
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts Broad Institute of MIT and Harvard, Cambridge, Massachusetts
    Cancer Immunol Res 3:855-63. 2015
    ..We discovered activating somatic and germline amino acid variants in JAK3 that promoted PD-L1 induction in lung cancer cells and in the tumor immune microenvironment...
  86. pmc JAK3/STAT6 Stimulates Bone Marrow-Derived Fibroblast Activation in Renal Fibrosis
    Jingyin Yan
    Division of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas
    J Am Soc Nephrol 26:3060-71. 2015
    ..In this study, we investigated the role of the Janus kinase 3 (JAK3)/signal transducer and activator of transcription (STAT6) signaling pathway in the activation of bone marrow-..
  87. doi Enhancing specificity in the Janus kinases: a study on the thienopyridine JAK2 selective mechanism combined molecular dynamics simulation
    Jiao Jiao Li
    College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, P R China
    Mol Biosyst 12:575-87. 2016
    The selective inhibition for JAK2 over the other JAK family kinases (JAK1, JAK3 and TYK2) has shared an immense challenge due to high conservatism...
  88. doi Deep intronic mis-splicing mutation in JAK3 gene underlies T-B+NK- severe combined immunodeficiency phenotype
    Polina Stepensky
    Pediatric Hematology Oncology and Bone Marrow Transplantation, Hadassah Hebrew University Medical Center, Jerusalem, Israel Electronic address
    Clin Immunol 163:91-5. 2016
    ..In this study we describe three patients with a novel deep intronic mis-splicing mutation in JAK3 as a cause of T-B+NK- SCID highlighting the need for careful evaluation of intronic regulatory elements of known ..
  89. doi Astilbin inhibits Th17 cell differentiation and ameliorates imiquimod-induced psoriasis-like skin lesions in BALB/c mice via Jak3/Stat3 signaling pathway
    Ting Ting Di
    Beijing University of Chinese Medicine, Beijing 100029, China
    Int Immunopharmacol 32:32-8. 2016
    ..Thus, astilbin likely alleviates psoriasis-like skin lesions by inhibiting Th17 related inflammation. Astilbin represents as an interesting candidate drug for immunoregulation of psoriasis. ..
  90. pmc miR-29b and miR-198 overexpression in CD8+ T cells of renal cell carcinoma patients down-modulates JAK3 and MCL-1 leading to immune dysfunction
    Margherita Gigante
    Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
    J Transl Med 14:84. 2016
    ....
  91. doi EZH2 phosphorylation by JAK3 mediates a switch to noncanonical function in natural killer/T-cell lymphoma
    Junli Yan
    Cancer Science Institute of Singapore, and
    Blood 128:948-58. 2016
    ..study, using natural killer/T-cell lymphoma (NKTL) as a disease model, we found that phosphorylation of EZH2 by JAK3 promotes the dissociation of the PRC2 complex leading to decreased global H3K27me3 levels, while it switches EZH2 ..
  92. doi The discovery of 2,5-isomers of triazole-pyrrolopyrimidine as selective Janus kinase 2 (JAK2) inhibitors versus JAK1 and JAK3
    Sun Mi Lee
    Department of Medical System Engineering, Gwangju Institute of Science and Technology GIST, 123 Cheomdan gwagiro, Buk Gu, Gwangju 61005, Republic of Korea
    Bioorg Med Chem 24:5036-5046. 2016
    ..9nM, fold selectivity JAK1/2 10.6 and JAK3/2 58.1). Compound 54 also exhibited an equivalent inhibition of wild type JAK2 and the V617F mutant...
  93. pmc Type II enteropathy-associated T-cell lymphoma features a unique genomic profile with highly recurrent SETD2 alterations
    Annalisa Roberti
    University Institute of Pathology, Service of Clinical Pathology, Centre Hospitalier Universitaire Vaudois, 25 rue du Bugnon, 1011 Lausanne, Switzerland
    Nat Commun 7:12602. 2016
    ..The JAK/STAT pathway comprises recurrent STAT5B (60%), JAK3 (46%) and SH2B3 (20%) mutations, including a STAT5B V712E activating variant...
  94. ncbi Spiro Meroterpenoids from Ganoderma applanatum
    Qi Luo
    State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, People s Republic of China
    J Nat Prod . 2016
    ..Biological evaluation of all the compounds disclosed that compounds 7 and 8 inhibited JAK3 kinase with IC50 values of 7.0 ± 3.2 and 34.8 ± 21.1 μM, respectively.
  95. doi Janus kinase inhibition for immunosuppression in solid organ transplantation: Is there a role in complex immunologic challenges?
    Cody A Moore
    Departments of Pharmacy and Therapeutics, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania Electronic address
    Hum Immunol . 2016
    ..in solid organ transplantation is appealing due to its specificity for immune cell function, particularly for JAK3. This is due to its unique association with only the common gamma chain (γc)...
  96. doi Dual role of IL-21 in megakaryopoiesis and platelet homeostasis
    Salima Benbarche
    Universite de Strasbourg, INSERM, EFS ALCA, BPPS UMR S 949, FMTS, Strasbourg, France
    Haematologica . 2017
    ..of CFU-MKs generated from CD34+ cells and the number of megakaryocyte differentiated from CD34+ progenitors in a JAK3- and STAT3-dependent manner...
  97. ncbi Structural organization and chromosomal mapping of JAK3 locus
    A Kumar
    The Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA
    Oncogene 13:2009-14. 1996
    In this study, we have isolated the genomic DNA clone encoding the murine JAK3 gene and determined its sequence...
  98. ncbi Molecular characterization of specific interactions between SHP-2 phosphatase and JAK tyrosine kinases
    T Yin
    Walther Oncology Center, Indiana University School of Medicine, Indianapolis 46202, USA
    J Biol Chem 272:1032-7. 1997
    ..In this study, we demonstrate that SHP-2 is tyrosine-phosphorylated by and associated with JAK1 and JAK2 but not JAK3 in COS-1 cell cotransfection experiments...
  99. ncbi STAM, signal transducing adaptor molecule, is associated with Janus kinases and involved in signaling for cell growth and c-myc induction
    T Takeshita
    Department of Microbiology, Tohoku University School of Medicine, Sendai, Japan
    Immunity 6:449-57. 1997
    ..STAM is associated with Jak3 and Jak2 tyrosine kinases via its ITAM region and phosphorylated by Jak3 and Jak2 upon stimulation with IL-2 and GM-..
  100. ncbi STAM2, a new member of the STAM family, binding to the Janus kinases
    K Endo
    Department of Microbiology, Tohoku University School of Medicine, Seiryo machi 2 1, Aoba ku, Sendai 980 8575, Japan
    FEBS Lett 477:55-61. 2000
    ..STAM2 like STAM1 is associated with Jak2 and Jak3, and involved in the signaling for DNA synthesis and c-myc induction mediated by IL-2 and GM-CSF...
  101. ncbi The upregulation by peplomycin of signal transduction in human cells
    T Yamamoto
    Department of Oral Surgery, Kochi Medical School, Nankoku City, Japan
    Jpn J Pharmacol 87:41-50. 2001
    ..These results indicate that PLM upregulates signal transduction in a variety of cell types and the upregulation may induce pulmonary fibrosis...

Research Grants61

  1. Jennifer M Puck; Fiscal Year: 2014
    ..pathway defects in the common g chain (gc) receptor, the IL-7 receptor a chain (IL7Ra), and Janus kinase 3 (Jak3), whereas the mouse knockouts lacking these proteins differ from humans in having T cells, but lacking B cells (T-B+..
  2. MECHANISMS OF ALLOGENEIC STEM CELL EDUCATION IN SCID
    Rebecca H Buckley; Fiscal Year: 2010
    ..by the development of normally functioning whether the decline in natural killer (NK) cell function in X-SCID and Jak3-deficient SCID is compensated for returning or new chimeras who are available during the two years of support, with ..
  3. JULIAN G CAMBRONERO; Fiscal Year: 2016
    ..The candidate kinases are VEGFR2 and JAK3, while the PDZ-Domain proteins are MUPP1 and Mda9/Syntenin...
  4. UTPAL P DAVE; Fiscal Year: 2016
    ..In support of this idea, we recently discovered gain of function mutations in JAK3 in 11% of ATLL patients and also noted frequent overexpression and kinase activation...
  5. Regulation of IL4 signal transduciton by poly (ADP-ribose) polymerase-1.
    Rahul Datta; Fiscal Year: 2011
    ..and expression of the various signal transduction components of IL-4 signal transduction pathway including JAK1, JAK3, STAT6, and GATA3. Western blotting will be used to examine levels of protein expression as well as phosphorylation...
  6. Sergei P Atamas; Fiscal Year: 2014
    ..Similar to IL- 4, IL-442 stimulates phosphorylation of Jak1, Jak3, and Tyk2 in T cells in a time- and dose-dependent fashion...
  7. Immunobiology of Jak3 Deficient Mice
    Leslie J Berg; Fiscal Year: 2010
    b>Jak3 is a protein kinase required for signaling through ctyokine receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21...
  8. IRS phosphorylation by type I IL-4R signaling and its role in allergic disease
    Nicola M Heller; Fiscal Year: 2010
    ..To this end, the role of unique components of the type I IL-4 receptor (gammaC chain and JAK3) in mediating strong tyrosine phosphorylation of IRS-2, a key adaptor molecule in this pathway, will be defined...
  9. Richard J Lamont; Fiscal Year: 2016
    ..gingivalis-stimulated cells demonstrated the association of JAK members JAK2, JAK3, and TYK2 with TLR2;(4) inhibition of JAK2 resulted in the loss of P...
  10. IRS phosphorylation by type I IL-4R signaling and its role in allergic disease
    Nicola M Heller; Fiscal Year: 2013
    ..The interval lay between aa318 and 323 and correlated with the association of activated JAK3 in the signaling complex...
  11. Role of Cytokine Signaling in Intestinal Restitution
    Narendra Kumar; Fiscal Year: 2013
    ..Recently we have shown for the first time that intestinal epithelial mucosa express functional Janus kinase 3 (Jak3) a non-receptor tyrosine kinase the biological functions of which were known to be limited to immune cells ( Kumar ..
  12. MECHANISMS OF ALLOGENEIC STEM CELL EDUCATION IN SCID
    Rebecca Buckley; Fiscal Year: 2003
    ..examine whether host dendritic cell abnormalities contribute to inadequate B and NK cell functions in X-linked and Jak3-deficient SCIDs...
  13. Christine Schwartz; Fiscal Year: 2014
    ..transcriptome sequencing shows that genes encoding regulatory proteins of well- known survival pathways, JAK3, STAT3, AKT1, MAPK1/3 are significantly upregulated during torpor and IBA...
  14. Structural biology of kinase signaling in T-cells
    Michael J Eck; Fiscal Year: 2010
    ..The importance of Jak3 in immune function is highlighted by the fact that inactivating mutations in this kinase result in severe combined ..
  15. REGULATION OF V(D)J RECOMBINATION IN B CELL DEVELOPMENT
    Rachel M Gerstein; Fiscal Year: 2011
    ..Specific Aim 1 is to determine the mechanism by the IL7R:JAK3:pSTAT5 pathway regulates the V(D)J recombinase...
  16. Jorg J Goronzy; Fiscal Year: 2015
    ..existing standard (methotrexate, leflunomide or TNF inhibition) and newly emerging treatment approaches such as JAK3 inhibition are able to correct the signaling abnormalities In Specific Aim 4, we will examine the functional ..
  17. Innate Immunity and SIV Infection
    Aftab A Ansari; Fiscal Year: 2013
    ..Our ability to functionally deplete this cell lineage in vivo during acute and/or chronic infection using a JAK3 inhibitor combined with our ability to in vitro expand and infuse large number of defined autologous NK cells and ..
  18. Notch-induced protein degradation in lymphopoiesis
    Xiao Hong Sun; Fiscal Year: 2013
    ..Specific aim #2 will delineate the role of Notch-induced E2A and Jak3 degradation in several lineage decisions during lymphoid development...
  19. T-cell growth factor pathways and immune modulation
    ROBERT KIRKEN; Fiscal Year: 2007
    ..is that active Stat5 transcription factors are critical for T cell modiated immunity, and that in addition to the Jak3 tyrosine kinase, a yet-to-be identified Stat5 serine kinase is also imporotant for mediating T cell responses...
  20. Jak/STAT signaling in human T-cell lymphomas
    Mariusz A Wasik; Fiscal Year: 2010
    ..The accumulated experimental evidence indicates that the Jak1/Jak3/STAT3/STAT5 signaling complex associated with the common g chain (gc) shared by several receptors stimulated by ..
  21. Modulation of tumor susceptibility to NK cells induced by JAK family genes
    Roberto Bellucci; Fiscal Year: 2012
    ..Jak2 were more susceptible to NK cell activity no effect was noticed with the other 2 members of the Jak family (Jak3 and TYK2)...
  22. DAVID MICHAEL LANGENAU; Fiscal Year: 2016
    ..lines that are deficient in forkhead box N l (foxnl/nude), recombination-activating gene 2 (rag2), Janus kinase 3 (jak3), DNA-dependent protein kinase (prkdc), and interieukin 2-receptor gamma (IL2rg)...
  23. NPM ALK mediated transformation of T lymphocytes
    David Levy; Fiscal Year: 2006
    ..We have also recently demonstrated that in human as well as in murine cells, NPM-ALK activates Jak3, Stat3, and Erk1-2 molecules...
  24. Breast tumor exosomal Jak3BP mediated immunosuppression
    Huang Ge Zhang; Fiscal Year: 2011
    ..We have identified a novel breast tumor exosomal protein (Jak3BP) that is capable of binding to Jak3 in the NK cells, resulting in the ubiquitination of Jak3...
  25. Development of UTL-5b for Rheumatoid Arthritis: Mechanism of Action
    Jiajiu Shaw; Fiscal Year: 2007
    ..activity of LPS- induced TNF alpha factor (LITAF), mitogen activated protein kinase kinase kinase 2 (Map3k2), and JAK3 tyrosine-protein kinase (JAK3) in arthritic paws, lymph nodes and spleens In addition to the preliminary MOA study, ..
  26. MECHANISMS OF IGE SYNTHESIS BY B CELLS
    Raif Geha; Fiscal Year: 2007
    ..The intracellular (IC) domain of CD40 has a binding site for Jak3, one for TRAF6 and one for the TRAF proteins TRAF2 and TRAF3 (TRAF2/3 site)...
  27. JAK-3 AND MYELOID CELL DIFFERENTIATION
    E Reddy; Fiscal Year: 2000
    ..The principal investigator has recently identified a new member of the JAK kinase family, named JAK3. JAK3 is selectively expressed in myeloid and lymphoid cells and appears to be a primary response gene induced by G-..
  28. PARACRINE REGULATION: SERTOLI/GERM CELL INTERACTIONS
    DR PATRICIA MORRIS; Fiscal Year: 2003
    ..both loss- and gain- of function experimental models to address the roles of STAT-4, STAT-6 and the tyrosine kinase JAK3 in meiotic and early haploid gene expression...
  29. MAST CELLS IN INNATE IMMUNITY AGAINST BACTERIAL INFECTIO
    Ravi Malaviya; Fiscal Year: 2001
    ..to be investigated is that specific biochemical signal transduction events involving the protein tyrosine kinase JAK3 are triggered by mast cell-gram negative bacteria interactions...
  30. MOLECULAR MECHANISMS CYTOKINE RECEPTOR SIGNALING
    Stephanie Watowich; Fiscal Year: 2000
    ..Chimeric EpoRs containing Jak1 or Jak3 binding domains will be generated and it will be determined if ligand-induced receptor dimerization activates the ..
  31. Curcumin inhibition of growth signaling in leukemia
    John Bright; Fiscal Year: 2004
    ..We will also examine the effect of curcumin on the constitutively active JAK3-STAT5 and IP3K-AKT signaling pathways and their links to the regulation of growth and apoptosis in T cell leukemia...
  32. Role of SOCS in Regulation of Transplantation Tolerance
    Stanislaw Stepkowski; Fiscal Year: 2004
    ..Th2)reg cells to test our hypothesis that tolerance depends upon the expansion of Th2reg cells with IL-4-driven Jak3/Stat5/Stat6 feedback loops...
  33. GENE THERAPY FOR SEVERE COMBINED IMMUNE DEFICIENCIES
    Kenneth Weinberg; Fiscal Year: 2000
    ..to mutations in the genes for the common gc cytokine receptor chain (X-linked SCID), adenosine deaminase (ADA), the JAK3 tyrosine kinase, the ZAP-70 tyrosine kinase, and the CIITA and RF-X proteins required for MHC proteins required for ..
  34. Role of IFN gamma in Th1 Cell Development
    Hua Huang; Fiscal Year: 2004
    ..and western blot analysis will be used to examine whether IL-4-induced phosphorylation of IL-4R alpha chain, Jak 1, Jak3 and STAT6 is greater in the IFNgammaR-/- Th1 cells...
  35. Negative regulation of TCR-associated PTKs
    ROBERT RICKERT; Fiscal Year: 2007
    ..will use the IL-2R system to test the notion that PTKs that do not depend on Src family kinases, such as Jakl and Jak3, are insensitive to loss of PEP...
  36. Signaling of IL-2Rgamma Cytokines
    Yu Chung Yang; Fiscal Year: 2006
    ..We have shown that (1) Tip60 (Tat-interacting protein, 60 kDa) can be tyrosine phosphorylated by Jak1 and Jak3 following IL-9, but not IL-4, stimulation, (2) Tip60 is rapidly degraded in an ubiquitination-dependent manner, and ..
  37. CYTOKINE SIGNALING AND ABL INDUCED TRANSFORMATION
    Paul Rothman; Fiscal Year: 2002
    ..This includes the activation of the Jak1 and Jak3 non- receptor tyrosine kinases and the STAT transcription factors which are normally activated by IL-4 and IL-7, ..
  38. T CELL SIGNAL TRANSDUCTION TO MONITOR HPV VACCINES
    Augusto Ochoa; Fiscal Year: 2001
    ....
  39. STRUCTURE/FUNCTION ANALYSIS OF JAK3 IN HUMAN SCID
    JOSEPH ROBERTS; Fiscal Year: 2001
    Deficiency of Janus family 3 (Jak3) tryosine kinase has recently been demonstrated to result in human SCID, a condition characterized by the absence of T and NK cells and non-functional B-cell signaling and to define functionally ..
  40. Treatment of Asthma by Targeting JAK3 with JANEX-1
    Alexei Vassilev; Fiscal Year: 2003
    ..It is our central working HYPOTHESIS that JAK3 plays a central role in the pathophysiology of allergic asthma and JAK3 inhibitors may be useful to prevent ..
  41. T CELL TARGETING FOR GVHD
    Bruce Blazar; Fiscal Year: 2007
    ..The second involves targeting intracellular signalling pathways[unreadable] (PI3K, Jak3) required for optimal T cell responses...
  42. Targeting JAK-3 with WHI-P97 for Treatment of Asthma
    Peter Samuel; Fiscal Year: 2003
    The rationally designed Janus kinase 3 (JAK3) inhibitor 4-(3',5'-dibromo-4'-hydroxyphenyl)- anmino-6,7-dirnethoxyquinazoline (WHI-P97) exhibits potent in vivo biologic activity in a mouse model of allergic asthma at nontoxic dose levels...
  43. Regulation of AV canal formation by the Jak-STAT pathway
    JAY POTTS; Fiscal Year: 2007
    ..that numerous members of the Jak-STAT pathway are localized to the AV canal, and that by blocking the function of Jak3 we can inhibit normal AV canal formation...
  44. Regulation of IL-4/IL-4R Signaling Pathway Mediate Tole*
    Stanislaw Stepkowski; Fiscal Year: 2003
    ..Th2 cells, which displayed reduced signaling through the intracellular molecules ERK2, NF-kappaB AP-1, Jak3, and Stat5...
  45. Role of Jak3 in Anaplastic Large Cell Lymphoma
    HESHAM AMIN; Fiscal Year: 2008
    ..Janus kinase 3 (Jak3) is a protein tyrosine kinase with biologic functions related to cell survival and tumorigenesis...
  46. Tumor-reactive IgG in the diagnosis of ovarian cancer
    Douglas Taylor; Fiscal Year: 2005
    ..Ultimately, antigenic proteins, linked with histologic type and stage of disease, will be combined into the development of protein arrays to screen for circulating reactive IgG as an early diagnostic test. ..
  47. PHI-381: A Novel Anti-Leukemic Agent
    Marina Cetkovic Cvrlje; Fiscal Year: 2003
    ..The knowledge gained from these studies described under Specific Aims 1-2 is expected to facilitate the design of innovative treatment regimens employing COBRA-1 for the treatment of metastatic solid tumors. ..
  48. Cytokine signal transduction in immune system
    Hodaka Fujii; Fiscal Year: 2007
    ..Detailed information gained from the proposed experiments will be valuable for elucidation of molecular mechanisms of oncogenesis and autoimmune diseases caused by dysregulation of cytokine signaling. ..
  49. Novel Approaches to the Assessment of Oral Mucosal Immu*
    Theresa Whiteside; Fiscal Year: 2003
    ..A better understanding of oral immunity in normal and HIV-infected mucosa is important for the development of new antiviral therapies, including oral antiviral vaccines. ..
  50. Role of Ubiquitin regulated F-Bx07 Protein in RA
    Huang Ge Zhang; Fiscal Year: 2003
    ..This will lead to a better understanding of the mechanisms underlying hyperproliferation of RASFs. ..
  51. Hematopoiesis
    James Ihle; Fiscal Year: 2004
    ..abstract_text> ..
  52. ANALYSIS OF BIDIRECTIONAL SIGNALING MECHANISMS FOR BTLA AND HVEM IN AUTOIMMUNITY
    Kenneth M Murphy; Fiscal Year: 2010
    ..Importantly, BTLA has recently been reported to be involved in the susceptibility in humans to rheumatoid arthritis. Thus, our proposed studies into this newly identified but poorly understood molecule are particularly timely. ..
  53. TRANSPLANT IMMUNOLOGY OF IL2 IFNY DOUBLE KNOCKOUT MICE
    Martin Zand; Fiscal Year: 2002
    ..In contrast, if the DKO mice are tolerant to islet allografts, we will determine the mechanism by adoptive transfer of tolerance inducing T lymphocyte subsets. ..
  54. DNA DAMAGE AND MUTAGENICITY OF OCHRATOXIN A
    Richard Manderville; Fiscal Year: 2002
    ....
  55. PHARMACOLOGY OF CYCLOSPORINE BASED IMMUNOSUPPRESSION
    Barry Kahan; Fiscal Year: 2004
    DESCRIPTION (provided by applicant):This project seeks to document that Janus kinase 3 (Jak3), an enzyme exclusively associated with the common y chain (yc) receptor used by a limited number of T-cell growth factors (interleukin [IL] -2, ..
  56. Effect of Drugs on Myocardial Hypoxia
    Garrett Gross; Fiscal Year: 2009
    ..Information gained from these studies will hopefully lead to new therapies to treat patients with ischemic heart disease. ..
  57. High Throughput Screen for JAK2V617F Mutant Selective Inhibitors
    Ross Levine; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  58. Periodontal Assessment in RA Study (PARAS)
    Clifton Bingham; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  59. Cytokine Regulated Growth Of Hematopoietic Cells
    James Ihle; Fiscal Year: 2007
    ..Both genetic approaches and biochemical approaches are proposed to identify components of this pathway. ..
  60. DNA-Based Vaccines for Oral Carcnoma
    Theresa Whiteside; Fiscal Year: 2005
    ....