Genomes and Genes
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
Publications274 found, 100 shown here
- Janus kinase 3: the controller and the controlledWei 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 ..
- Reconstitution of early lymphoid proliferation and immune function in Jak3-deficient mice by interleukin-3M 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...
- Recent patents in the discovery of small molecule inhibitors of JAK3Lawrence 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 ..
- Unusual clinical and immunologic manifestations of transplacentally acquired maternal T cells in severe combined immunodeficiencyKricia 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...
- Activation of JAK3, but not JAK1, is critical to interleukin-4 (IL4) stimulated proliferation and requires a membrane-proximal region of IL4 receptor alphaM 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. 1995The 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 ..
- Janus kinases in immune cell signalingKamran 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. 2009The Janus family kinases (Jaks), Jak1, Jak2, Jak3, and Tyk2, form one subgroup of the non-receptor protein tyrosine kinases...
- Ligand-independent homomeric and heteromeric complexes between interleukin-2 or -9 receptor subunits and the gamma chainYaniv 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)...
- Unexpected and variable phenotypes in a family with JAK3 deficiencyD M Frucht
Arthritis and Rheumatism Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, Bethesda, MD, USA
Genes Immun 2:422-32. 2001Mutations 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 ..
- NSC114792, a novel small molecule identified through structure-based computational database screening, selectively inhibits JAK3Byung Hak Kim
Department of Pediatrics, Division of Hematology Oncology, New York Medical College, Valhalla, New York 10595, USA
Mol Cancer 9:36. 2010Human 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...
- Impaired NFAT regulation and its role in a severe combined immunodeficiencyS Feske
The Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA
Immunobiology 202:134-50. 2000....
- Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitutionRebecca 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 ..
- Mutations causing severe combined immunodeficiency: detection with a custom resequencing microarrayTonya 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...
- Specificities of CD40 signaling: involvement of TRAF2 in CD40-induced NF-kappaB activation and intercellular adhesion molecule-1 up-regulationH 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...
- Regulation of IGF-I mRNA and signal transducers and activators of transcription-3 and -5 (Stat-3 and -5) by GH in C2C12 myoblastsRobert 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 ..
- Aberrant expression of interleukin-7 (IL-7) and its signalling complex in human breast cancerM 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...
- 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 reportJoel 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), ..
- Mechanism of inflammation in murine eosinophilic myocarditis produced by adoptive transfer with ovalbumin challengeMasao 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...
- Direct interaction between Kit and the interleukin-7 receptorThomas 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...
- New concepts in phospholipase D signaling in inflammation and cancerJulian 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...
- Signalling by cytokines interacting with the interleukin-2 receptor gamma chainJ 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...
- Transcription factor STAT5A is a substrate of Bruton's tyrosine kinase in B cellsS 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...
- Partial restoration of B cell development in Jak-3(-/-) mice achieved by co-expression of IgH and E(mu)-myc transgenesStacey 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...
- 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 knoShinichiro 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...
- T cell development and activation in Jak3-deficient miceA M Baird
Department of Pathology, University of Massachusetts Medical Center, Worcester 01655, USA
J Leukoc Biol 63:669-77. 1998b>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...
- Dysregulated myelopoiesis in mice lacking Jak3W 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. 1999b>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...
- Growth hormone receptor interaction with Jak proteins differs between tissuesG 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...
- Interleukin 7 induces the growth of breast cancer cells through a wortmannin-sensitive pathwayM 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...
- BLNK suppresses pre-B-cell leukemogenesis through inhibition of JAK3Joji 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 ..
- Tumor-shed PGE(2) impairs IL2Rgammac-signaling to inhibit CD4 T cell survival: regulation by theaflavinsSreya Chattopadhyay
Division of Molecular Medicine, Bose Institute, P 1 12 CIT Scheme VIIM, Kolkata, India
PLoS ONE 4:e7382. 2009....
- Immunolocalisation of the janus kinases (JAK)--signal transducers and activators of transcription (STAT) pathway in human epidermisH 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 ..
- The common gamma chain (gamma c) is a required signaling component of the IL-21 receptor and supports IL-21-induced cell proliferation via JAK3Tania 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)..
- Induction of 15-lipoxygenase expression by IL-13 requires tyrosine phosphorylation of Jak2 and Tyk2 in human monocytesB 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...
- Characterization of the cytoplasmic domain of interleukin-13 receptor-alphaP 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-..
- Functional involvement of Akt signaling downstream of Jak1 in v-Abl-induced activation of hematopoietic cellsShinji 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 ..
- 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...
- Role of Janus kinase-2 in IgE receptor-mediated leukotriene C4 production by mast cellsRuna 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...
- 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 miceK 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-..
- Functional uncoupling of the Janus kinase 3-Stat5 pathway in malignant growth of human T cell leukemia virus type 1-transformed human T cellsR 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...
- Developmental defects of lymphoid cells in Jak3 kinase-deficient miceS Y Park
Division of Molecular Genetics, Chiba University School of Medicine, Japan
Immunity 3:771-82. 1995b>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...
- Thrombin induces expression of cytokine-induced SH2 protein (CIS) in rat brain astrocytes: involvement of phospholipase A2, cyclooxygenase, and lipoxygenaseKyung 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...
- Immunosuppression by the JAK3 inhibitor CP-690,550 delays rejection and significantly prolongs kidney allograft survival in nonhuman primatesDominic 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. 2005Janus kinase 3 (JAK3) mediates signal transduction from cytokine receptors using the common chain (gammac)...
- [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....
- The interleukin-4 receptor activates STAT5 by a mechanism that relies upon common gamma-chainA Lischke
Theodor Boveri Institut für Biowissenschaften Biozentrum, Physiologische Chemie II, Am Hubland, D 97074 Wurzburg, Germany
J Biol Chem 273:31222-9. 1998Interleukin (IL)-4 signaling proceeds via cytoplasmic activation of the Janus kinases JAK1 and JAK3 and the signal transducer and activator of transcription STAT6...
- New strategies for immunosuppression: interfering with cytokines by targeting the Jak/Stat pathwayJOHN 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...
- Phase 1 dose-escalation study of CP-690 550 in stable renal allograft recipients: preliminary findings of safety, tolerability, effects on lymphocyte subsets and pharmacokineticsE 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...
- Acute lymphoblastic leukemia-associated JAK1 mutants activate the Janus kinase/STAT pathway via interleukin-9 receptor alpha homodimersTekla 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)...
- Downregulation of Janus kinase 3 expression by small interfering RNA in rat composite tissue allotransplantationKao 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...
- 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 kinaseFatih M Uckun
Developmental Therapeutics Program, Institute for Pediatric Clinical Research, Childrens Hospital Los Angeles, CA, USA
Arzneimittelforschung 60:218-25. 2010The 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)...
- Constitutive activation of a slowly migrating isoform of Stat3 in mycosis fungoides: tyrphostin AG490 inhibits Stat3 activation and growth of mycosis fungoides tumor cell linesM 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...
- The immunosuppressive metabolite of leflunomide, A77 1726, affects murine T cells through two biochemical mechanismsR 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...
- Molecular cloning of a chicken JAK homolog from activated T cellsL 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.
- Effects of Th2 cytokines on chemokine expression in the lung: IL-13 potently induces eotaxin expression by airway epithelial cellsL 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, ..
- Altered natural killer cell differentiation in CD34+ progenitors from chronic myeloid leukemia patientsG 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...
- Advances in the understanding and treatment of human severe combined immunodeficiencyR 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...
- A newly identified AMSH-family protein is specifically expressed in haploid stages of testicular germ cellsKeiko 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...
- 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 mannerWatchara 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. 2005We 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 ..
- JAK-STAT signaling pathway in pulmonary arterial smooth muscle cells is activated by hypoxiaGuan 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)...
- Development of pyrimidine-based inhibitors of Janus tyrosine kinase 3Jack 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. 2006A new class of pyrimidine-based Janus tyrosine kinase 3 (JAK3) inhibitors are described. Many of these inhibitors showed low nanomolar activity against JAK3.
- Stat5 is essential for early B cell development but not for B cell maturation and functionXuezhi 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...
- Receptor expression is essential for proliferation induced by dimerized Jak kinasesHodaka 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. 2008Two 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 ..
- Permission to proceed: Jak3 and STAT5 signaling molecules give the green light for T helper 1 cell differentiationKenneth 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. 2008In 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.
- Multiple Gi proteins participate in nerve growth factor-induced activation of c-Jun N-terminal kinases in PC12 cellsPrudence 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...
- Janus kinase-3 dependent inflammatory responses in allergic asthmaRama 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...
- 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. 2011Janus 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...
- JAK-mutant myeloproliferative neoplasmsRoss L Levine
Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
Curr Top Microbiol Immunol 355:119-33. 2012Although 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 ..
- Inhibitory effects of the JAK inhibitor CP690,550 on human CD4(+) T lymphocyte cytokine productionKiyoshi Migita
Department of Rheumatology and Clinical Research Center, NHO Nagasaki Medical Center, Kubara 2 1001 1, Omura 856 8652, Japan
BMC Immunol 12:51. 2011The 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.
- RGS2 is a negative regulator of STAT3-mediated Nox1 expressionHyung 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)...
- Protection of porcine endothelial cells against apoptosis with interleukin-4Sylvester 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...
- JAK3, STAT3 and CD3-zeta signaling proteins status in regard to the lymphocytes function in patients with ovarian cancerMagdalena 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...
- The genetic basis of early T-cell precursor acute lymphoblastic leukaemiaJinghui 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 ..
- An N-ethyl-N-nitrosourea (ENU)-induced dominant negative mutation in the JAK3 kinase protects against cerebral malariaSilayuv 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)...
- Cucurbitacins as inducers of cell death and a rich source of potential anticancer compoundsJ 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 ..
- Effective elicitation of human effector CD8+ T Cells in HLA-B*51:01 transgenic humanized mice after infection with HIV-1Yoshinori 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 ..
- Biologics and other novel approaches as new therapeutic options in myasthenia gravis: a view to the futureMarinos 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...
- 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. ..
- Inhibition of IL-6 family cytokines by SOCS3Jeffrey 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...
- FRA2 is a STAT5 target gene regulated by IL-2 in human CD4 T cellsAradhana 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...
- Downregulation of chloride channel ClC-2 by Janus kinase 3Jamshed Warsi
Department of Physiology I, University of Tubingen, Gmelinstr 5, 72076, Tubingen, Germany
J Membr Biol 247:387-93. 2014Janus 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...
- Adapter protein Shc regulates Janus kinase 3 phosphorylationJayshree 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. 2014Although constitutive activation of Janus kinase 3 (Jak3) leads to different cancers, the mechanism of trans-molecular regulation of Jak3 activation is not known...
- ATP-mediated kinome selectivity: the missing link in understanding the contribution of individual JAK Kinase isoforms to cellular signalingAtli 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...
- WHI-P154 enhances the chemotherapeutic effect of anticancer agents in ABCG2-overexpressing cellsHui 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...
- Novel hinge-binding motifs for Janus kinase 3 inhibitors: a comprehensive structure-activity relationship study on tofacitinib bioisosteresMatthias 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 ..
- Vanadium pentoxide prevents NK-92MI cell proliferation and IFNγ secretion through sustained JAK3 phosphorylationFrancisco 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 ..
- Piperine blocks interleukin-2-driven cell cycle progression in CTLL-2 T lymphocytes by inhibiting multiple signal transduction pathwaysCarolyn 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 ..
- Long-term Benefit of PD-L1 Blockade in Lung Cancer Associated with JAK3 ActivationEliezer 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...
- JAK3/STAT6 Stimulates Bone Marrow-Derived Fibroblast Activation in Renal FibrosisJingyin 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-..
- Enhancing specificity in the Janus kinases: a study on the thienopyridine JAK2 selective mechanism combined molecular dynamics simulationJiao Jiao Li
College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, P R China
Mol Biosyst 12:575-87. 2016The selective inhibition for JAK2 over the other JAK family kinases (JAK1, JAK3 and TYK2) has shared an immense challenge due to high conservatism...
- Deep intronic mis-splicing mutation in JAK3 gene underlies T-B+NK- severe combined immunodeficiency phenotypePolina 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 ..
- Astilbin inhibits Th17 cell differentiation and ameliorates imiquimod-induced psoriasis-like skin lesions in BALB/c mice via Jak3/Stat3 signaling pathwayTing 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. ..
- miR-29b and miR-198 overexpression in CD8+ T cells of renal cell carcinoma patients down-modulates JAK3 and MCL-1 leading to immune dysfunctionMargherita Gigante
Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
J Transl Med 14:84. 2016....
- EZH2 phosphorylation by JAK3 mediates a switch to noncanonical function in natural killer/T-cell lymphomaJunli 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 ..
- The discovery of 2,5-isomers of triazole-pyrrolopyrimidine as selective Janus kinase 2 (JAK2) inhibitors versus JAK1 and JAK3Sun 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...
- Type II enteropathy-associated T-cell lymphoma features a unique genomic profile with highly recurrent SETD2 alterationsAnnalisa 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...
- Spiro Meroterpenoids from Ganoderma applanatumQi 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.
- 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)...
- Dual role of IL-21 in megakaryopoiesis and platelet homeostasisSalima 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...
- Structural organization and chromosomal mapping of JAK3 locusA Kumar
The Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA
Oncogene 13:2009-14. 1996In this study, we have isolated the genomic DNA clone encoding the murine JAK3 gene and determined its sequence...
- Molecular characterization of specific interactions between SHP-2 phosphatase and JAK tyrosine kinasesT 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...
- STAM, signal transducing adaptor molecule, is associated with Janus kinases and involved in signaling for cell growth and c-myc inductionT 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-..
- STAM2, a new member of the STAM family, binding to the Janus kinasesK 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...
- The upregulation by peplomycin of signal transduction in human cellsT 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...
- 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+..
- MECHANISMS OF ALLOGENEIC STEM CELL EDUCATION IN SCIDRebecca 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 ..
- JULIAN G CAMBRONERO; Fiscal Year: 2016..The candidate kinases are VEGFR2 and JAK3, while the PDZ-Domain proteins are MUPP1 and Mda9/Syntenin...
- 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...
- 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...
- 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...
- Immunobiology of Jak3 Deficient MiceLeslie J Berg; Fiscal Year: 2010b>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...
- IRS phosphorylation by type I IL-4R signaling and its role in allergic diseaseNicola 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...
- 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...
- IRS phosphorylation by type I IL-4R signaling and its role in allergic diseaseNicola M Heller; Fiscal Year: 2013..The interval lay between aa318 and 323 and correlated with the association of activated JAK3 in the signaling complex...
- Role of Cytokine Signaling in Intestinal RestitutionNarendra 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 ..
- MECHANISMS OF ALLOGENEIC STEM CELL EDUCATION IN SCIDRebecca 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...
- 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...
- Structural biology of kinase signaling in T-cellsMichael 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 ..
- REGULATION OF V(D)J RECOMBINATION IN B CELL DEVELOPMENTRachel 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...
- 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 ..
- Innate Immunity and SIV InfectionAftab 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 ..
- Notch-induced protein degradation in lymphopoiesisXiao 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...
- T-cell growth factor pathways and immune modulationROBERT 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...
- Jak/STAT signaling in human T-cell lymphomasMariusz 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 ..
- Modulation of tumor susceptibility to NK cells induced by JAK family genesRoberto 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)...
- 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)...
- NPM ALK mediated transformation of T lymphocytesDavid 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...
- Breast tumor exosomal Jak3BP mediated immunosuppressionHuang 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...
- Development of UTL-5b for Rheumatoid Arthritis: Mechanism of ActionJiajiu 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, ..
- MECHANISMS OF IGE SYNTHESIS BY B CELLSRaif 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)...
- JAK-3 AND MYELOID CELL DIFFERENTIATIONE 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-..
- PARACRINE REGULATION: SERTOLI/GERM CELL INTERACTIONSDR 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...
- MAST CELLS IN INNATE IMMUNITY AGAINST BACTERIAL INFECTIORavi 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...
- MOLECULAR MECHANISMS CYTOKINE RECEPTOR SIGNALINGStephanie 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 ..
- Curcumin inhibition of growth signaling in leukemiaJohn 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...
- Role of SOCS in Regulation of Transplantation ToleranceStanislaw 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...
- GENE THERAPY FOR SEVERE COMBINED IMMUNE DEFICIENCIESKenneth 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 ..
- Role of IFN gamma in Th1 Cell DevelopmentHua 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...
- Negative regulation of TCR-associated PTKsROBERT 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...
- Signaling of IL-2Rgamma CytokinesYu 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 ..
- CYTOKINE SIGNALING AND ABL INDUCED TRANSFORMATIONPaul 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, ..
- T CELL SIGNAL TRANSDUCTION TO MONITOR HPV VACCINESAugusto Ochoa; Fiscal Year: 2001....
- STRUCTURE/FUNCTION ANALYSIS OF JAK3 IN HUMAN SCIDJOSEPH ROBERTS; Fiscal Year: 2001Deficiency 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 ..
- Treatment of Asthma by Targeting JAK3 with JANEX-1Alexei 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 ..
- T CELL TARGETING FOR GVHDBruce Blazar; Fiscal Year: 2007..The second involves targeting intracellular signalling pathways[unreadable] (PI3K, Jak3) required for optimal T cell responses...
- Targeting JAK-3 with WHI-P97 for Treatment of AsthmaPeter Samuel; Fiscal Year: 2003The 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...
- Regulation of AV canal formation by the Jak-STAT pathwayJAY 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...
- 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...
- Role of Jak3 in Anaplastic Large Cell LymphomaHESHAM AMIN; Fiscal Year: 2008..Janus kinase 3 (Jak3) is a protein tyrosine kinase with biologic functions related to cell survival and tumorigenesis...
- Tumor-reactive IgG in the diagnosis of ovarian cancerDouglas 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. ..
- PHI-381: A Novel Anti-Leukemic AgentMarina 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. ..
- Cytokine signal transduction in immune systemHodaka 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. ..
- 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. ..
- Role of Ubiquitin regulated F-Bx07 Protein in RAHuang Ge Zhang; Fiscal Year: 2003..This will lead to a better understanding of the mechanisms underlying hyperproliferation of RASFs. ..
- HematopoiesisJames Ihle; Fiscal Year: 2004..abstract_text> ..
- ANALYSIS OF BIDIRECTIONAL SIGNALING MECHANISMS FOR BTLA AND HVEM IN AUTOIMMUNITYKenneth 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. ..
- TRANSPLANT IMMUNOLOGY OF IL2 IFNY DOUBLE KNOCKOUT MICEMartin 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. ..
- DNA DAMAGE AND MUTAGENICITY OF OCHRATOXIN ARichard Manderville; Fiscal Year: 2002....
- PHARMACOLOGY OF CYCLOSPORINE BASED IMMUNOSUPPRESSIONBarry Kahan; Fiscal Year: 2004DESCRIPTION (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, ..
- Effect of Drugs on Myocardial HypoxiaGarrett Gross; Fiscal Year: 2009..Information gained from these studies will hopefully lead to new therapies to treat patients with ischemic heart disease. ..
- High Throughput Screen for JAK2V617F Mutant Selective InhibitorsRoss Levine; Fiscal Year: 2008..unreadable] [unreadable] [unreadable]..
- Periodontal Assessment in RA Study (PARAS)Clifton Bingham; Fiscal Year: 2007..unreadable] [unreadable] [unreadable] [unreadable]..
- Cytokine Regulated Growth Of Hematopoietic CellsJames Ihle; Fiscal Year: 2007..Both genetic approaches and biochemical approaches are proposed to identify components of this pathway. ..
- DNA-Based Vaccines for Oral CarcnomaTheresa Whiteside; Fiscal Year: 2005....