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
Products:     Jak3

Top Publications

  1. Wu W, Sun X. Janus kinase 3: the controller and the controlled. Acta Biochim Biophys Sin (Shanghai). 2012;44:187-96 pubmed publisher
    ..In particular, JAK3 has unique functions in the lymphoid system such that JAK3 ablation results in phenotypes resembling severe ..
  2. Han M, Ji X, Li G, Sang N. NO2 inhalation enhances asthma susceptibility in a rat model. Environ Sci Pollut Res Int. 2017;24:27843-27854 pubmed publisher
    ..transducer and activator of transcription-6 (IL-4/STAT6) pathway [IL-4 receptor (IL-4R) α, janus kinase (JAK) 1, JAK 3, and STAT6] and related transcription factor [T cell-specific protein-tyrosine kinase (Lck), extracellular-..
  3. Wu P, Jiang W, Jiang J, Zhao J, Liu Y, Zhang Y, et al. Dietary choline deficiency and excess induced intestinal inflammation and alteration of intestinal tight junction protein transcription potentially by modulating NF-?B, STAT and p38 MAPK signaling molecules in juvenile Jian carp. Fish Shellfish Immunol. 2016;58:462-473 pubmed publisher
    ..In summary, dietary choline deficiency or excess caused the depression of intestinal mucosal immune by inducing inflammation and dysfunction of the intestinal physical barrier, and regulating related signaling molecules of fish. ..
  4. Zhang H, Watanabe R, Berry G, Tian L, Goronzy J, Weyand C. Inhibition of JAK-STAT Signaling Suppresses Pathogenic Immune Responses in Medium and Large Vessel Vasculitis. Circulation. 2018;137:1934-1948 pubmed publisher
    ..T cells are sensitive to the cytokine-signaling inhibitor tofacitinib, a Janus kinase (JAK) inhibitor targeting JAK3 and JAK1...
  5. Gomez Cambronero J. New concepts in phospholipase D signaling in inflammation and cancer. ScientificWorldJournal. 2010;10:1356-69 pubmed publisher
    ..They are Y296, Y415, and Y511 and the responsible kinases are, respectively, EGFR, JAK3, and Src...
  6. Ezeh P, Xu H, Lauer F, Liu K, Hudson L, Burchiel S. Monomethylarsonous acid (MMA+3) Inhibits IL-7 Signaling in Mouse Pre-B Cells. Toxicol Sci. 2016;149:289-99 pubmed publisher
    ..found selective inhibition of STAT5 phosphorylation by MMA(+3), and this inhibition was dependent on effects on JAK3 phosphorylation...
  7. Wu P, Liu Y, Jiang W, Jiang J, Zhang Y, Zhou X, et al. Intestinal immune responses of Jian carp against Aeromonas hydrophila depressed by choline deficiency: Varied change patterns of mRNA levels of cytokines, tight junction proteins and related signaling molecules among three intestinal segments. Fish Shellfish Immunol. 2017;65:34-41 pubmed publisher
    ..primary response 88 (MyD88), nuclear factor kappa B (NF-?B), inhibitor of NF-?B (I?B), Janus kinase 3 (JAK3), and signal transducers and activators of transcription 5 (STAT5)], tight junction proteins (claudin 3b, claudin ..
  8. Malemud C. Suppression of Autoimmune Arthritis by Small Molecule Inhibitors of the JAK/STAT Pathway. Pharmaceuticals (Basel). 2010;3:1446-1455 pubmed
    ..A few JAK-specific SMIs have made their way into RA clinical trials. In fact, the JAK3-specific SMI, CP-690,500 is the first JAK/STAT SMI to be assessed for clinical efficacy in a Phase III RA trial.
  9. Doucette C, Greenshields A, Liwski R, Hoskin D. Piperine blocks interleukin-2-driven cell cycle progression in CTLL-2 T lymphocytes by inhibiting multiple signal transduction pathways. Toxicol Lett. 2015;234:1-12 pubmed publisher
    ..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 ..

More Information

Publications141 found, 100 shown here

  1. Katz G, Pobezinsky L, Jeurling S, Shinzawa M, Van Laethem F, Singer A. T cell receptor stimulation impairs IL-7 receptor signaling by inducing expression of the microRNA miR-17 to target Janus kinase 1. Sci Signal. 2014;7:ra83 pubmed publisher
    ..The initial event in IL-7 signaling is the transactivation of Janus kinases 1 and 3 (Jak1 and Jak3), which are associated with the cytosolic tails of the IL-7 receptor α chain (IL-7Rα) and the γc subunit, ..
  2. Zetterberg C, Maltais F, Laitinen L, Liao S, Tsao H, Chakilam A, et al. VX-509 (Decernotinib)-Mediated CYP3A Time-Dependent Inhibition: An Aldehyde Oxidase Metabolite as a Perpetrator of Drug-Drug Interactions. Drug Metab Dispos. 2016;44:1286-95 pubmed publisher
  3. Dai S, Gu H, Lin Q, Xing T, Chen M, Zhong T, et al. Disequilibrium in the CD8+CD28+/CD8+CD28- T Lymphocyte Balance Is Related to Prognosis in Rats with Trinitrobenzenesulfonic Acid-Induced Colitis. Dig Dis Sci. 2017;62:639-651 pubmed publisher
    ..Immunohistochemistry and Western blotting were used to detect the colonic expression of JAK3, STAT6, NFATc2, and GATA3...
  4. Xie X, Di T, Wang Y, Wang M, Meng Y, Lin Y, et al. Indirubin ameliorates imiquimod-induced psoriasis-like skin lesions in mice by inhibiting inflammatory responses mediated by IL-17A-producing γδ T cells. Mol Immunol. 2018;101:386-395 pubmed publisher
    ..The IL-17 expression and secretion, and the activation of Jak3/Stat3 pathways in in vitro cultured γδ T cell were tested...
  5. Batista L, Utsunomiya Y, Silva T, Dias R, Tomokane T, Pacheco A, et al. Genome-Wide Association Study of Cell-Mediated Response in Dogs Naturally Infected by Leishmania infantum. Infect Immun. 2016;84:3629-3637 pubmed
    ..GWAS showed that regions associated with TNF-? include the following genes: IL12RB1, JAK3, CCRL2, CCR2, CCR3, and CXCR6, involved in cytokine and chemokine signaling; regions associated with LST, including ..
  6. Rani A, Greenlaw R, Runglall M, Jurcevic S, John S. FRA2 is a STAT5 target gene regulated by IL-2 in human CD4 T cells. PLoS ONE. 2014;9:e90370 pubmed publisher
    ..Furthermore, addition of JAK3 inhibitor (R333) or Daclizumab inhibited the induction in TCR stimulated cells...
  7. Feng X, Shen S, Cao P, Zhu L, Zhang Y, Zheng K, et al. The role of oncostatin M regulates osteoblastic differentiation of dental pulp stem cells through STAT3 pathway. Cytotechnology. 2016;68:2699-2709 pubmed
    ..In summary, OSM promotes osteoblastic differentiation of DPSCs and osteogenesis-related genes expression through the JAK3/STAT3 signaling pathway which may be useful for the autologous transplantation of DPSCs.
  8. Lang E, Lang F. Mechanisms and pathophysiological significance of eryptosis, the suicidal erythrocyte death. Semin Cell Dev Biol. 2015;39:35-42 pubmed publisher
    ..g. ampk, gk, pak2, ck1α, jak3, pkc, p38-mapk)...
  9. Nakamura D, Yoshimitsu M, Kuroki A, Hachiman M, Kamada Y, Ezinne C, et al. A new ATL xenograft model and evaluation of pyrrolidine dithiocarbamate as a potential ATL therapeutic agent. Exp Hematol. 2015;43:944-50 pubmed publisher
    ..cells (PBMCs) isolated from ATL patients (ATL cells) into nonobese diabetic/severe combined immunodeficiency/Jak3-null mice (NOJ mice). To generate the model, the ATL S1T cell line was subcutaneously injected into mice...
  10. Logan S, Tessier S, Tye J, Storey K. Response of the JAK-STAT pathway to mammalian hibernation in 13-lined ground squirrel striated muscle. Mol Cell Biochem. 2016;414:115-27 pubmed publisher
    ..Immunoblots showed a fivefold decrease in JAK3 expression during torpor in skeletal muscle, along with increases in STAT3 and 5 phosphorylation and suppressors of ..
  11. Tamarit B, Bugault F, Pillet A, Lavergne V, Bochet P, Garin N, et al. Membrane microdomains and cytoskeleton organization shape and regulate the IL-7 receptor signalosome in human CD4 T-cells. J Biol Chem. 2013;288:8691-701 pubmed publisher
    ..We show that lipid raft inhibitors delay and reduce IL-7-induced JAK1 and JAK3 phosphorylation...
  12. Cheng Y, Zhang X, Sun Y, Wang W, Huang J, Chu N, et al. Genomewide DNA Methylation Responses in Patients with ?-Thalassemia Treated with Yisui Shengxue Granules (). Chin J Integr Med. 2018;: pubmed publisher
    ..Genes of insulin-like growth factor 1 receptor (IGF1R) and Janus kinase 3 (JAK3) revealed the most relations with other genes (degree: 21) and genes of 1-phosphatidylinositol-4, 5-bisphosphate ..
  13. Calama E, Ramis I, Domènech A, Carreño C, De Alba J, Prats N, et al. Tofacitinib ameliorates inflammation in a rat model of airway neutrophilia induced by inhaled LPS. Pulm Pharmacol Ther. 2017;43:60-67 pubmed publisher
    ..Four JAK proteins, JAK1, JAK2, JAK3 and tyrosine kinase 2 (Tyk2) associate with the intracellular domains of surface cytokine receptors are ..
  14. Barrett J, Minogue A, Falvey A, Lynch M. Involvement of IGF-1 and Akt in M1/M2 activation state in bone marrow-derived macrophages. Exp Cell Res. 2015;335:258-68 pubmed publisher
    ..b>JAK3 is activated as a consequence of ligation of the type I IL-4R, which participates in Akt activation...
  15. Haddad E, Logan B, Griffith L, Buckley R, Parrott R, Prockop S, et al. SCID genotype and 6-month post-transplant CD4 count predict survival and immune recovery: a PIDTC retrospective study. Blood. 2018;: pubmed publisher
    ..Overall survival was similar for patients with RAG, IL2RG or JAK3 defects, and was significantly better compared to patients with ADA or DCLRE1C mutations...
  16. Ge S, Zhang J, Du Y, Hu B, Zhou Z, Lou J. Dynamic changes in the gene expression profile during rat oral carcinogenesis induced by 4-nitroquinoline 1-oxide. Mol Med Rep. 2016;13:2561-9 pubmed publisher
    ..In addition, this comprehensive investigation provided a theoretical basis for the understanding of the molecular alterations associated with oral carcinogenesis. ..
  17. Cheng Y, Chikwava K, Wu C, Zhang H, Bhagat A, Pei D, et al. LNK/SH2B3 regulates IL-7 receptor signaling in normal and malignant B-progenitors. J Clin Invest. 2016;126:1267-81 pubmed publisher
    ..homeostasis by attenuating IL-7-stimuated JAK/STAT5 signaling via a direct interaction with phosphorylated JAK3. Moreover, JAK inhibitors were effective in prolonging survival of mice transplanted with Lnk-/-Tp53-/- leukemia...
  18. Lin J, Leonard W. The Common Cytokine Receptor ? Chain Family of Cytokines. Cold Spring Harb Perspect Biol. 2017;: pubmed publisher
    ..Janus kinase (JAK)3 associates with ?c, and JAK3-deficient SCID phenocopies XSCID, findings that served to stimulate the development of JAK3 inhibitors as ..
  19. Vely F, Barlogis V, Vallentin B, Neven B, Piperoglou C, Ebbo M, et al. Evidence of innate lymphoid cell redundancy in humans. Nat Immunol. 2016;17:1291-1299 pubmed publisher
    ..of the gene encoding the common γ-chain cytokine receptor subunit IL-2Rγ or the gene encoding the tyrosine kinase JAK3. T cell reconstitution was observed in patients with SCID after hematopoietic stem cell transplantation (HSCT), but ..
  20. He X, Sun D, Chen S, Xu H. Activation of liver X receptor delayed the retinal degeneration of rd1 mice through modulation of the immunological function of glia. Oncotarget. 2017;8:32068-32082 pubmed publisher
    ..Our data suggested that T0 modulated the immunologic function of glia cells in the degenerative retina through the JAK3/STAT pathway and delayed the apoptosis of photoreceptors.
  21. Tanimoto A, Ogawa Y, Oki C, Kimoto Y, Nozawa K, Amano W, et al. Pharmacological properties of JTE-052: a novel potent JAK inhibitor that suppresses various inflammatory responses in vitro and in vivo. Inflamm Res. 2015;64:41-51 pubmed publisher
    ..JTE-052 inhibited the JAK1, JAK2, JAK3, and tyrosine kinase (Tyk)2 enzymes in an adenosine triphosphate (ATP)-competitive manner and inhibited cytokine ..
  22. Shu G, Zhao W, Yue L, Su H, Xiang M. Antitumor immunostimulatory activity of polysaccharides from Salvia chinensis Benth. J Ethnopharmacol. 2015;168:237-47 pubmed publisher
    ..In CD4+ T cells, PSSC substantially declined intracellular cAMP. This event elevated protein levels of JAK3, enhancing STAT5 phosphorylation and STAT5-dependent expression of anti-apoptotic genes...
  23. Ruiz Medina B, Ross J, Kirken R. Interleukin-2 Receptor β Thr-450 Phosphorylation Is a Positive Regulator for Receptor Complex Stability and Activation of Signaling Molecules. J Biol Chem. 2015;290:20972-83 pubmed publisher
    ..Reconstitution assays demonstrated that Thr-450 is important for regulating IL-2R complex formation, recruitment of JAK3, and activation of AKT and ERK1/2 and a transcriptionally active STAT5...
  24. Huan W, Tianzhu Z, Yu L, Shumin W. Effects of Ergosterol on COPD in Mice via JAK3/STAT3/NF-κB Pathway. Inflammation. 2017;40:884-893 pubmed publisher
    ..Furthermore, ER significantly inhibited the protein expression of JAK3/STAT3/NF-κB pathway in CS-induced mice...
  25. Karaczyn A, Cheng R, Buzard G, Hartley J, Esposito D, Kasprzak K. Truncation of histone H2A's C-terminal tail, as is typical for Ni(II)-assisted specific peptide bond hydrolysis, has gene expression altering effects. Ann Clin Lab Sci. 2009;39:251-62 pubmed
    ..Many of the differentially expressed genes, including BAZ2A, CLDN18, CYP51A1, GFR, GIPC2, HMGB1, IRF7, JAK3, PSIP1, and VEGF, are cancer-related genes...
  26. Majri S, Fritz J, Villarino A, Zheng L, Kanellopoulou C, Chaigne Delalande B, et al. STAT5B: A Differential Regulator of the Life and Death of CD4+ Effector Memory T Cells. J Immunol. 2018;200:110-118 pubmed publisher
    ..TEM cell death was prevented with neutralizing anti-IL-2 Ab or STAT5/JAK3 inhibitors, indicating that STAT5 signaling drives RICD in TEM cells...
  27. Qiu L, Lai R, Lin Q, Lau E, Thomazy D, Calame D, et al. Autocrine release of interleukin-9 promotes Jak3-dependent survival of ALK+ anaplastic large-cell lymphoma cells. Blood. 2006;108:2407-15 pubmed
    ..We previously demonstrated that Jak3 potentiates the activity of NPM-ALK...
  28. Jeong E, Kim M, Nam H, Min C, Lee S, Chung Y, et al. Somatic mutations of JAK1 and JAK3 in acute leukemias and solid cancers. Clin Cancer Res. 2008;14:3716-21 pubmed publisher
    The aim of this study was to see whether JAK1, JAK3, and TYK2 genes are altered in human cancers...
  29. Shuh M, Morse B, Heidecker G, Derse D. Association of SRC-related kinase Lyn with the interleukin-2 receptor and its role in maintaining constitutive phosphorylation of JAK/STAT in human T-cell leukemia virus type 1-transformed T cells. J Virol. 2011;85:4623-7 pubmed publisher
    ..Lyn coimmunoprecipitates with the interleukin-2 beta receptor (IL-2R?) and JAK3 proteins; however, the association of Lyn with the IL-2R? and Lyn kinase activity was independent of IL-2 ..
  30. Mitiushova E, Shatrova A, Zenin V, Aksenov N, Marakhova I. [The STAT5 signaling in the expression of alpha-subunit of interleukin-2 receptor in human blood lymphocytes]. Tsitologiia. 2013;55:421-9 pubmed
    ..WHI-P131, an inhibitor of JAK3 kinase, prevents STAT5 activation, cell surface expression of CD25 and lymphocyte proliferation...
  31. Abolhassani H, Cheraghi T, Rezaei N, Aghamohammadi A, Hammarström L -. Common Variable Immunodeficiency or Late-Onset Combined Immunodeficiency: A New Hypomorphic JAK3 Patient and Review of the Literature. J Investig Allergol Clin Immunol. 2015;25:218-20 pubmed
  32. Sibbesen N, Kopp K, Litvinov I, Jønson L, Willerslev Olsen A, Fredholm S, et al. Jak3, STAT3, and STAT5 inhibit expression of miR-22, a novel tumor suppressor microRNA, in cutaneous T-Cell lymphoma. Oncotarget. 2015;6:20555-69 pubmed
    Aberrant activation of Janus kinase-3 (Jak3) and its key down-stream effectors, Signal Transducer and Activator of Transcription-3 (STAT3) and STAT5, is a key feature of malignant transformation in cutaneous T-cell lymphoma (CTCL)...
  33. Stepensky P, Keller B, Shamriz O, NaserEddin A, Rumman N, Weintraub M, et al. Deep intronic mis-splicing mutation in JAK3 gene underlies T-B+NK- severe combined immunodeficiency phenotype. Clin Immunol. 2016;163:91-5 pubmed publisher
    ..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 ..
  34. Liang X, Huang Y, Zang J, Gao Q, Wang B, Xu W, et al. Design, synthesis and preliminary biological evaluation of 4-aminopyrazole derivatives as novel and potent JAKs inhibitors. Bioorg Med Chem. 2016;24:2660-72 pubmed publisher
    ..17m possessed the highest protein kinase inhibitory rates (%) at 10?M, which were 97, 96 and 100 to JAK1, JAK2 and JAK3, respectively. Further evaluation revealed that the IC50 values of 17m against JAK1, JAK2 and JAK3 were 0.67?M, 0...
  35. Takeshita T, Arita T, Higuchi M, Asao H, Endo K, Kuroda H, et al. STAM, signal transducing adaptor molecule, is associated with Janus kinases and involved in signaling for cell growth and c-myc induction. Immunity. 1997;6:449-57 pubmed
    ..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-..
  36. Goedken E, Argiriadi M, Banach D, Fiamengo B, Foley S, Frank K, et al. Tricyclic covalent inhibitors selectively target Jak3 through an active site thiol. J Biol Chem. 2015;290:4573-89 pubmed publisher
    ..However, due to high similarity in the active sites of the four members (Jak1, Jak2, Jak3, and Tyk2), developing selective inhibitors within this family is challenging...
  37. Tan L, Akahane K, McNally R, Reyskens K, Ficarro S, Liu S, et al. Development of Selective Covalent Janus Kinase 3 Inhibitors. J Med Chem. 2015;58:6589-606 pubmed publisher
    ..Here we report the discovery and optimization of 2,4-substituted pyrimidines as covalent JAK3 inhibitors that exploit a unique cysteine (Cys909) residue in JAK3...
  38. Nakamura S, Kahyo T, Tao H, Shibata K, Kurabe N, Yamada H, et al. Novel roles for LIX1L in promoting cancer cell proliferation through ROS1-mediated LIX1L phosphorylation. Sci Rep. 2015;5:13474 pubmed publisher
    ..Moreover, ROS1, HCK, ABL1, ABL2, JAK3, LCK and TYR03 were identified as candidate kinases responsible for the phosphorylation of Tyr(136) of LIX1L...
  39. Lee S, Choi J, Han B, Kim H, Song H, Lee J, et al. Crystal structures of spleen tyrosine kinase in complex with novel inhibitors: structural insights for design of anticancer drugs. FEBS J. 2016;283:3613-3625 pubmed publisher
    ..7-33 nm, but they showed dissimilar inhibitory activities against KDR, RET, JAK2, JAK3, and FLT3...
  40. Roberti A, Dobay M, Bisig B, Vallois D, Boéchat C, Lanitis E, et al. Type II enteropathy-associated T-cell lymphoma features a unique genomic profile with highly recurrent SETD2 alterations. Nat Commun. 2016;7:12602 pubmed publisher
    ..The JAK/STAT pathway comprises recurrent STAT5B (60%), JAK3 (46%) and SH2B3 (20%) mutations, including a STAT5B V712E activating variant...
  41. Miyazaki T, Takaoka A, Nogueira L, Dikic I, Fujii H, Tsujino S, et al. Pyk2 is a downstream mediator of the IL-2 receptor-coupled Jak signaling pathway. Genes Dev. 1998;12:770-5 pubmed
    ..The interleukin-2 receptor (IL-2R) is associated with the Jak1 and Jak3 PTKs, and ligand-induced activation of these PTKs is essential for lymphocyte proliferation...
  42. Roberts J, Lengi A, Brown S, Chen M, Zhou Y, O Shea J, et al. Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients and outcomes of stem cell transplantation. Blood. 2004;103:2009-18 pubmed
    ..families among 170 severe combined immunodeficiency (SCID) patients who exhibited 9 different Janus kinase 3 (JAK3) mutations. These included 3 missense and 2 nonsense mutations, 1 insertion, and 3 deletions...
  43. Han Y, Amin H, Franko B, Frantz C, Shi X, Lai R. Loss of SHP1 enhances JAK3/STAT3 signaling and decreases proteosome degradation of JAK3 and NPM-ALK in ALK+ anaplastic large-cell lymphoma. Blood. 2006;108:2796-803 pubmed
    ..Expression of SHP1 in these 2 cell lines also resulted in marked decreases in the protein levels of JAK3 and NPM-ALK, and these effects were reversible by proteosome inhibitor MG132...
  44. De Vita S, Mulligan C, McElwaine S, Dagna Bricarelli F, Spinelli M, Basso G, et al. Loss-of-function JAK3 mutations in TMD and AMKL of Down syndrome. Br J Haematol. 2007;137:337-41 pubmed
    Acquired mutations activating Janus kinase 3 (jak3) have been reported in Down syndrome (DS) and non-DS patients with acute megakaryoblastic leukaemia (AMKL)...
  45. Roskoski R. Janus kinase (JAK) inhibitors in the treatment of inflammatory and neoplastic diseases. Pharmacol Res. 2016;111:784-803 pubmed publisher
    The Janus kinase (JAK) family of non-receptor protein-tyrosine kinases consists of JAK1, JAK2, JAK3, and TYK2 (tyrosine kinase-2)...
  46. Li M, Lai D, Zhao H, Chen Z, Huang Q, Situ J. SOCS3 overexpression enhances ADM resistance in bladder cancer T24 cells. Eur Rev Med Pharmacol Sci. 2017;21:3005-3011 pubmed
    ..ADM drug resistant cell line T24/ADM was established. SOCS3, p-JAK2, p-JAK3, and Bcl-2 expressions in T24/ADM, T24, and HBEC cells were compared...
  47. Liao H, Li T, Chen C, Chen H, Chen W, Lai C, et al. Janus kinase-1 and 3 in ankylosing spondylitis. J Formos Med Assoc. 2019;118:134-141 pubmed publisher
    ..These findings have also suggested that JAK-1 and JAK-3 expression may play a role in the inflammatory processes in patients with AS. ..
  48. Witthuhn B, Silvennoinen O, Miura O, Lai K, Cwik C, Liu E, et al. Involvement of the Jak-3 Janus kinase in signalling by interleukins 2 and 4 in lymphoid and myeloid cells. Nature. 1994;370:153-7 pubmed
    ..Jak-3 activation requires the serine-rich, membrane-proximal domain of the interleukin-2 receptor beta-chain, but does not require the acidic domain that is required for association and activation of Src family kinases. ..
  49. Fujitani Y, Hibi M, Fukada T, Takahashi Tezuka M, Yoshida H, Yamaguchi T, et al. An alternative pathway for STAT activation that is mediated by the direct interaction between JAK and STAT. Oncogene. 1997;14:751-61 pubmed
    ..In the process we found that the JH2 domain of JAK1, JAK2 or JAK3 could specifically associate with the carboxy-terminal portion of STAT5, but not with STAT3 or STAT1...
  50. Cohney S, Sanden D, Cacalano N, Yoshimura A, Mui A, Migone T, et al. SOCS-3 is tyrosine phosphorylated in response to interleukin-2 and suppresses STAT5 phosphorylation and lymphocyte proliferation. Mol Cell Biol. 1999;19:4980-8 pubmed
    ..Tyrosine phosphorylation of SOCS-3 was observed upon coexpression with Jak1 and Jak2 but only weakly with Jak3. In these experiments, SOCS-3 associated with Jak1 and inhibited Jak1 phosphorylation, and this inhibition was ..
  51. Kryworuchko M, Pasquier V, Theze J. Human immunodeficiency virus-1 envelope glycoproteins and anti-CD4 antibodies inhibit interleukin-2-induced Jak/STAT signalling in human CD4 T lymphocytes. Clin Exp Immunol. 2003;131:422-7 pubmed
    ..This Jak/STAT deficiency may contribute to the crippling of CD4 T cell responses to a cytokine central to the immune response by HIV. ..
  52. Henriques C, Rino J, Nibbs R, Graham G, Barata J. IL-7 induces rapid clathrin-mediated internalization and JAK3-dependent degradation of IL-7Ralpha in T cells. Blood. 2010;115:3269-77 pubmed publisher
    ..In turn, pretreatment of T cells with JAK3 or pan-JAK inhibitors suggests that IL-7Ralpha degradation depends on the activation of the IL-7 signaling effector ..
  53. Lai K, Jin Y, Graham D, Witthuhn B, Ihle J, Liu E. A kinase-deficient splice variant of the human JAK3 is expressed in hematopoietic and epithelial cancer cells. J Biol Chem. 1995;270:25028-36 pubmed
    ..Recently, the kinase partners for the interleukin (IL)-2 receptor have been identified as JAK1 and JAK3. In this study, we report the identification of splice variants that may modulate JAK3 signaling...
  54. Auer F, Ingenhag D, Pinkert S, Kracker S, Hacein Bey Abina S, Cavazzana M, et al. Activation-induced cytidine deaminase prevents pro-B cell acute lymphoblastic leukemia by functioning as a negative regulator in Rag1 deficient pro-B cells. Oncotarget. 2017;8:75797-75807 pubmed publisher
    ..Additional whole exome/sanger sequencing of murine pro-B ALLs revealed an accumulation of recurrent somatic Jak3 (p.R653H, p.V670A) and Dnm2 (p...
  55. Russell S, Tayebi N, Nakajima H, Riedy M, Roberts J, Aman M, et al. Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development. Science. 1995;270:797-800 pubmed
    ..The Janus family tyrosine kinase Jak3 is the only signaling molecule known to be associated with gamma c, so it was hypothesized that defects in Jak3 ..
  56. Rashid S, Bibi N, Parveen Z, Shafique S. Inhibition of Janus kinases by tyrosine phosphorylation inhibitor, Tyrphostin AG-490. J Biomol Struct Dyn. 2015;33:2368-79 pubmed publisher
    ..molecular dynamics simulation assays, we explored comparative binding patterns of AG-490 against JAK1, JAK2, and JAK3. Our results entail noteworthy observations about the binding affinity of AG-490 by illustrating distinctive amino ..
  57. Losdyck E, Hornakova T, Springuel L, Degryse S, Gielen O, Cools J, et al. Distinct Acute Lymphoblastic Leukemia (ALL)-associated Janus Kinase 3 (JAK3) Mutants Exhibit Different Cytokine-Receptor Requirements and JAK Inhibitor Specificities. J Biol Chem. 2015;290:29022-34 pubmed publisher
    JAK1 and JAK3 are recurrently mutated in acute lymphoblastic leukemia...
  58. Zyuz kov G, Zhdanov V, Udut E, Miroshnichenko L, Simanina E, Polyakova T, et al. Implication of JAK1, JAK2, and JAK3 in the Realization of Proliferation and Differentiation Potential of Mesenchymal Progenitor Cells In Vitro. Bull Exp Biol Med. 2016;161:224-7 pubmed publisher
    ..Important role of JAK2 and JAK3 in determining the initial level of mitotic activity of progenitor cells was established...
  59. Martina M, Ramírez Bajo M, Bañón Maneus E, Moya Rull D, Hierro Garcia N, Revuelta I, et al. Inhibition of JAK3 and PKC via Immunosuppressive Drugs Tofacitinib and Sotrastaurin Inhibits Proliferation of Human B Lymphocytes In Vitro. Transplant Proc. 2016;48:3046-3052 pubmed publisher
    ..This study evaluated the impact of JAK3 and PKC inhibitors tofacitinib (Tofa) and sotrastaurin (STN), respectively, on B-cell proliferation, apoptosis, and ..
  60. Macchi P, Villa A, Giliani S, Sacco M, Frattini A, Porta F, et al. Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID). Nature. 1995;377:65-8 pubmed
    ..Both mutations resulted in markedly reduced levels of Jak-3. These findings show that abnormalities in the Jak/STAT signalling pathway can account for SCID in humans. ..
  61. Shatrova A, Mityushova E, Vassilieva I, Aksenov N, Zenin V, Nikolsky N, et al. Time-Dependent Regulation of IL-2R ?-Chain (CD25) Expression by TCR Signal Strength and IL-2-Induced STAT5 Signaling in Activated Human Blood T Lymphocytes. PLoS ONE. 2016;11:e0167215 pubmed publisher
    ..Based on the inhibitory effect of WHI-P131, a selective drug of JAK3 kinase activity, we concluded that in quiescent primary T lymphocytes, the constitutive STAT3 and the IL-2-induced ..
  62. Wang Y, Cui X, Chuang Y, Chen S. Janus Kinase 3, a Novel Regulator for Smooth Muscle Proliferation and Vascular Remodeling. Arterioscler Thromb Vasc Biol. 2017;37:1352-1360 pubmed publisher
    ..The objective of this study is to determine the role and mechanism of Janus kinase 3 (JAK3) in vascular remodeling and SMC proliferation...
  63. Yamagishi H, Shirakami S, Nakajima Y, Tanaka A, Takahashi F, Hamaguchi H, et al. Discovery of 3,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-2(1H)-one derivatives as novel JAK inhibitors. Bioorg Med Chem. 2015;23:4846-59 pubmed publisher
    ..To identify JAK inhibitors, we focused on the 1H-pyrrolo[2,3-b]pyridine derivative 3, which exhibited moderate JAK3 and JAK1 inhibitory activities...
  64. Chang C, Lai Y, Westin E, Khodadadi Jamayran A, Pawlik K, Lamb L, et al. Modeling Human Severe Combined Immunodeficiency and Correction by CRISPR/Cas9-Enhanced Gene Targeting. Cell Rep. 2015;12:1668-77 pubmed publisher
    Mutations of the Janus family kinase JAK3 gene cause severe combined immunodeficiency (SCID)...
  65. Yang Z, Ahn H, Park Y, Nam H. Afatinib Reduces STAT6 Signaling of Host ARPE-19 Cells Infected with Toxoplasma gondii. Korean J Parasitol. 2016;54:31-8 pubmed publisher
    ..Both JAK1 and JAK3, the upper hierarchical kinases of cytokine signaling, were strongly phosphorylated at 2 hr and then disappeared ..
  66. Deng J, Pennati A, Cohen J, Wu Y, Ng S, Wu J, et al. GIFT4 fusokine converts leukemic B cells into immune helper cells. J Transl Med. 2016;14:106 pubmed publisher
    ..GIFT4 treatment led to JAK1, JAK2 and JAK3-mediated hyper-phosphorylation of STAT5 in primary CLL cells, which is essential for GIFT4-triggered conversion of ..
  67. Ayars M, O Sullivan E, Macgregor Das A, Shindo K, Kim H, Borges M, et al. IL2RG, identified as overexpressed by RNA-seq profiling of pancreatic intraepithelial neoplasia, mediates pancreatic cancer growth. Oncotarget. 2017;8:83370-83383 pubmed publisher
    ..in orthotopically implanted pancreatic cancer cells resulted in attenuated tumor growth in mice and reduced JAK3 expression in orthotopic tumors...
  68. Mishra J, Karanki S, Kumar N. Identification of molecular switch regulating interactions of Janus kinase 3 with cytoskeletal proteins. J Biol Chem. 2012;287:41386-91 pubmed publisher
    Janus kinase 3 (Jak3) is a nonreceptor tyrosine kinase expressed in both hematopoietic and nonhematopoietic cells...
  69. van der Weyden L, Giotopoulos G, Wong K, Rust A, Robles Espinoza C, Osaki H, et al. Somatic drivers of B-ALL in a model of ETV6-RUNX1; Pax5(+/-) leukemia. BMC Cancer. 2015;15:585 pubmed publisher
    ..signaling pathway (Jak1, Stat5 and Il2rb), while exome sequencing revealed somatic hotspot mutations in Jak1 and Jak3 at residues analogous to those mutated in human leukemias, and also mutation of Trp53...
  70. Lee S, Yoon K, Lee H, Kim J, Chung Y, Cho W, et al. The discovery of 2,5-isomers of triazole-pyrrolopyrimidine as selective Janus kinase 2 (JAK2) inhibitors versus JAK1 and JAK3. Bioorg Med Chem. 2016;24:5036-5046 pubmed publisher
    ..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...
  71. Sato T, Okano T, Tanaka Kubota M, Kimura S, Miyamoto S, Ono S, et al. Novel compound heterozygous mutations in a Japanese girl with Janus kinase 3 deficiency. Pediatr Int. 2016;58:1076-1080 pubmed publisher
    ..Mutations in several genes cause SCID, one of which is Janus kinase 3 (JAK3), resulting in autosomal recessive T(-)B(+)NK(-) SCID...
  72. Zhang Z, Liu F, Li Z, Wang D, Li R, Sun C. Jak3 is involved in CCR7-dependent migration and invasion in metastatic squamous cell carcinoma of the head and neck. Oncol Lett. 2017;13:3191-3197 pubmed publisher
    ..present study, the metastatic SCCHN PCI-37B cell line was utilized to explore the role of Janus activated kinase-3 (Jak3) in the CCR7-mediated signaling pathway in metastatic SCCHN cells...
  73. Zhou Y, Magnuson K, Cheng T, Gadina M, Frucht D, Galon J, et al. Hierarchy of protein tyrosine kinases in interleukin-2 (IL-2) signaling: activation of syk depends on Jak3; however, neither Syk nor Lck is required for IL-2-mediated STAT activation. Mol Cell Biol. 2000;20:4371-80 pubmed
    ..We therefore investigated the functional relationships among Jak3, Lck, and Syk in IL-2 signaling...
  74. Kaur M, Singh P, Singh M, Bahadur R, Silakari O. Molecular dynamics and integrated pharmacophore-based identification of dual [Formula: see text] inhibitors. Mol Divers. 2018;22:95-112 pubmed publisher
    ..The present study is aimed to identify dual JAK3/[Formula: see text] inhibitors by developing an optimum pharmacophore model integrating the information revealed by ..
  75. Vila Coro A, Rodriguez Frade J, Martín de Ana A, Moreno Ortíz M, Martinez A C, Mellado M. The chemokine SDF-1alpha triggers CXCR4 receptor dimerization and activates the JAK/STAT pathway. FASEB J. 1999;13:1699-710 pubmed
    ..CXCR4 receptor becomes tyrosine phosphorylated through the activation and association with the receptor of JAK2 and JAK3 kinases...
  76. Saharinen P, Silvennoinen O. The pseudokinase domain is required for suppression of basal activity of Jak2 and Jak3 tyrosine kinases and for cytokine-inducible activation of signal transduction. J Biol Chem. 2002;277:47954-63 pubmed
    ..Here, we found that the JH2 domain negatively regulates the activity of Jak2 and Jak3. Deletion of JH2 resulted in increased tyrosine phosphorylation of the Jak2- and Jak3-JH2 deletion mutants as well ..
  77. Recher M, Berglund L, Avery D, Cowan M, Gennery A, Smart J, et al. IL-21 is the primary common ? chain-binding cytokine required for human B-cell differentiation in vivo. Blood. 2011;118:6824-35 pubmed publisher
    SCID resulting from mutations in IL2RG or JAK3 is characterized by lack of T and natural killer cells; B cells are present in normal number, but antibody responses are defective...
  78. Li S, Ma M, Li H, Waluszko A, Sidorenko T, Schadt E, et al. Cancer gene profiling in non-small cell lung cancers reveals activating mutations in JAK2 and JAK3 with therapeutic implications. Genome Med. 2017;9:89 pubmed publisher
    ..V617F mutation could confer sensitivity to both JAK inhibitors and anti-PD1 immunotherapy. We also detected JAK3 germline activating mutations in 6...
  79. Rolling C, Treton D, Beckmann P, Galanaud P, Richard Y. JAK3 associates with the human interleukin 4 receptor and is tyrosine phosphorylated following receptor triggering. Oncogene. 1995;10:1757-61 pubmed
    ..We demonstrate that IL4R triggering induced the tyrosine phosphorylation of JAK3 and of a p170 protein...
  80. Kim S, Choi J, Lim H, Lee S, Kim W, Cho S, et al. EGF-induced MMP-9 expression is mediated by the JAK3/ERK pathway, but not by the JAK3/STAT-3 pathway in a SKBR3 breast cancer cell line. Cell Signal. 2009;21:892-8 pubmed
    ..In this study, we investigated the novel function of the JAK3 inhibitor, WHI-P131, on EGF-induced MMP-9 expression and the regulatory mechanism of EGF-induced MMP-9 expression ..
  81. Guo Y, Arakawa F, Miyoshi H, Niino D, Kawano R, Ohshima K. Activated janus kinase 3 expression not by activating mutations identified in natural killer/T-cell lymphoma. Pathol Int. 2014;64:263-6 pubmed publisher
    Janus Kinase 3 (JAK3) is a non-receptor tyrosine kinase, predominantly expressed in hematopoietic cells, that plays an essential role in hematopoiesis during T cell development...
  82. Robinette M, Cella M, Telliez J, Ulland T, Barrow A, Capuder K, et al. Jak3 deficiency blocks innate lymphoid cell development. Mucosal Immunol. 2018;11:50-60 pubmed publisher
    Loss-of-function mutations in the tyrosine kinase JAK3 cause autosomal recessive severe combined immunodeficiency (SCID)...
  83. Sheikh A, Hooda O, Dang A. JAK3 and PI3K mediate bovine Interferon-tau stimulated gene expression in the blood neutrophils. J Cell Physiol. 2018;233:4885-4894 pubmed publisher
    ..incubated simultaneously with 10 ng/ml of recombinant bovine interferon tau and the inhibitors of JAK2 (AG490), JAK3 (CP690550), p38 (SB202190), PI3K/Akt (LY294002), and MAPK/Erk (U0126) at specific doses for 4-hr duration...
  84. Ross J, Cheng H, Nagy Z, Frost J, Kirken R. Protein phosphatase 2A regulates interleukin-2 receptor complex formation and JAK3/STAT5 activation. J Biol Chem. 2010;285:3582-91 pubmed publisher
    ..phosphorylation plays a key role in interleukin-2 (IL-2) receptor-mediated activation of Janus tyrosine kinase 3 (JAK3) and signal transducer and activator of transcription 5 (STAT5) in lymphocytes...
  85. Chrencik J, Patny A, Leung I, Korniski B, Emmons T, Hall T, et al. Structural and thermodynamic characterization of the TYK2 and JAK3 kinase domains in complex with CP-690550 and CMP-6. J Mol Biol. 2010;400:413-33 pubmed publisher
    ..kinase domains have been reported recently with the clinical compound CP-690550, the structures of both TYK2 and JAK3 with CP-690550 have remained outstanding...
  86. Zheng T, Kang J, Sim J, Kim J, Koh J, Shin C, et al. The farnesoid X receptor negatively regulates osteoclastogenesis in bone remodeling and pathological bone loss. Oncotarget. 2017;8:76558-76573 pubmed publisher
    ..We further suggested that interference of IFN-? expression by FXR deficiency impaired the downstream JAK3-STAT1 signaling pathways, which in turn increased osteoclast formation...
  87. Jiang H, Foltenyi K, Kashiwada M, Donahue L, Vuong B, Hehn B, et al. Fes mediates the IL-4 activation of insulin receptor substrate-2 and cellular proliferation. J Immunol. 2001;166:2627-34 pubmed
    ..Fes appears to be a downstream kinase from Jak1/Jak3 in this process...
  88. Yamada T, Zhu D, Saxon A, Zhang K. CD45 controls interleukin-4-mediated IgE class switch recombination in human B cells through its function as a Janus kinase phosphatase. J Biol Chem. 2002;277:28830-5 pubmed
    ..class switching were concomitant with the ability of CD45 to dephosphorylate the induced phosphorylation of JAK1, JAK3, and signal transducer and activator of transcription 6, but not on stress-activated/mitogen-activated protein ..
  89. Kameda T, Shide K, Shimoda H, Hidaka T, Kubuki Y, Katayose K, et al. Absence of gain-of-function JAK1 and JAK3 mutations in adult T cell leukemia/lymphoma. Int J Hematol. 2010;92:320-5 pubmed publisher
    Janus kinase 1 (JAK1) and JAK3 plays a critical role in lymphocyte proliferation and differentiation. Somatic JAK1 mutations are found in 18% of adult precursor T acute lymphoblastic leukemias and somatic JAK3 mutations are found in 3...
  90. Bhavsar S, Gu S, Bobbala D, Lang F. Janus kinase 3 is expressed in erythrocytes, phosphorylated upon energy depletion and involved in the regulation of suicidal erythrocyte death. Cell Physiol Biochem. 2011;27:547-56 pubmed publisher
    ..Janus kinase 3, a tyrosine kinase expressed in haematopoetic tissues, plays a decisive role in T-lymphocyte survival. JAK3 deficiency leads to (Severe) Combined Immunodeficiency (SCID) resulting from enhanced lymphocyte apoptosis...
  91. Feng J, Li Y, Jia Y, Fang Q, Gong X, Dong X, et al. Spectrum of somatic mutations detected by targeted next-generation sequencing and their prognostic significance in adult patients with acute lymphoblastic leukemia. J Hematol Oncol. 2017;10:61 pubmed publisher
    ..9%) harbored at least one mutation. The five most frequently mutated genes in T-ALL are NOTCH1, JAK3, FBXW7, FAT1, and NRAS. In B-ALL, FAT1, SF1, CRLF2, TET2, and PTPN1 have higher incidence of mutations...
  92. Ge Y, Wang C, Song S, Huang J, Liu Z, Li Y, et al. Identification of highly potent BTK and JAK3 dual inhibitors with improved activity for the treatment of B-cell lymphoma. Eur J Med Chem. 2018;143:1847-1857 pubmed publisher
    The BTK and JAK3 receptor tyrosine kinases are two validated and therapeutically amenable targets in the treatment of B-cell lymphomas...