Jak3

Summary

Gene Symbol: Jak3
Description: Janus kinase 3
Alias: RATJAK3, tyrosine-protein kinase JAK3, JAK-3, Janus kinase 3, protein-tyrosine kinase
Species: rat
Products:     Jak3

Top Publications

  1. 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. ..
  2. Bergmann A, Schneppenheim S, Seifert M, Betts M, Haake A, Lopez C, et al. Recurrent mutation of JAK3 in T-cell prolymphocytic leukemia. Genes Chromosomes Cancer. 2014;53:309-16 pubmed publisher
    ..However, these primary genetic events are insufficient to drive leukemogenesis. Recently, activating mutations in JAK3 have been identified in other T-cell malignancies...
  3. Sakaguchi H, Okuno Y, Muramatsu H, Yoshida K, Shiraishi Y, Takahashi M, et al. Exome sequencing identifies secondary mutations of SETBP1 and JAK3 in juvenile myelomonocytic leukemia. Nat Genet. 2013;45:937-41 pubmed publisher
    ..The SETBP1 and JAK3 genes were among common targets for secondary mutations...
  4. Deuse T, Hua X, Taylor V, Stubbendorff M, Baluom M, Chen Y, et al. Significant reduction of acute cardiac allograft rejection by selective janus kinase-1/3 inhibition using R507 and R545. Transplantation. 2012;94:695-702 pubmed publisher
    ..Both R507 and R545 are potent novel immunosuppressants with favorable pharmacokinetics and high JAK1/3 selectivity, but only R507 synergistically interacts with Tac. ..
  5. Kaminski A, Welters H, Kaminski E, Morgan N. Human and rodent pancreatic beta-cells express IL-4 receptors and IL-4 protects against beta-cell apoptosis by activation of the PI3K and JAK/STAT pathways. Biosci Rep. 2009;30:169-75 pubmed publisher
    ..of STAT6 (signal transducer and activator of transcription 6) also occurred in response to IL-4 and a selective JAK3 (Janus kinase 3) inhibitor reduced the cytoprotective response...
  6. Yamaoka K, Min B, Zhou Y, Paul W, O Shea J. Jak3 negatively regulates dendritic-cell cytokine production and survival. Blood. 2005;106:3227-33 pubmed
    Cytokines are critical in regulating the development and function of diverse cells. Janus kinase 3 (Jak3) is a tyrosine kinase expressed in hematopoietic cells that associates with the common gamma chain (gammac) and is required for ..
  7. Sohn S, Forbush K, Nguyen N, Witthuhn B, Nosaka T, Ihle J, et al. Requirement for Jak3 in mature T cells: its role in regulation of T cell homeostasis. J Immunol. 1998;160:2130-8 pubmed
    The tyrosine kinase Jak3 plays a key role in transducing signals from the IL-2, -4, -7, -9, and -15 receptors. Mice lacking Jak3 exhibit a profound, early block in both B and T cell development...
  8. Ross J, Spadaro M, Rosado D, Cavallo F, Kirken R, Pericle F. Inhibition of JAK3 with a novel, selective and orally active small molecule induces therapeutic response in T-cell malignancies. Leukemia. 2014;28:941-4 pubmed publisher
  9. Wang G, Qian P, Xu Z, Zhang J, Wang Y, Cheng S, et al. Regulatory effects of the JAK3/STAT1 pathway on the release of secreted phospholipase A?-IIA in microvascular endothelial cells of the injured brain. J Neuroinflammation. 2012;9:170 pubmed publisher
    ..The release of sPLA2-IIA, and the expression of inducible nitric oxide synthase (iNOS), phospho-JAK3, phospho-STAT1, total JAK3 and STAT1, ?-actin, and bovine serum albumin (BSA) were analyzed by Western blot or ..

Scientific Experts

More Information

Publications45

  1. Zhong D, Zhao X, Hao J, Guo H. [The role of Janus kinase/signal transducer and activator of transcription 3 in injury of alveolar type II epithelial cells of rat with severe acute pancreatitis in vitro]. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2009;21:107-10 pubmed
    ..48+/-0.10 vs. 0.69+/-0.02, P<0.01), and the apoptosis of AT II increased [(13.92+/-0.82)% vs. (11.55+/-1.10)%, P<0.05]. The results suggest that JAK/STAT3 pathway might be involved in the pathogenesis of injury to AT II in SAP. ..
  2. Simoncic P, Lee Loy A, Barber D, Tremblay M, McGlade C. The T cell protein tyrosine phosphatase is a negative regulator of janus family kinases 1 and 3. Curr Biol. 2002;12:446-53 pubmed
    ..We have identified two members of the Janus family of tyrosine kinases (JAKs), JAK1 and JAK3, as bona fide substrates of TCPTP...
  3. Mizuno M, Kondo E, Nishimura M, Ueda Y, Yoshiya I, Tohyama M, et al. Localization of molecules involved in cytokine receptor signaling in the rat trigeminal ganglion. Brain Res Mol Brain Res. 1997;44:163-6 pubmed
    ..In addition, JAK3 immunoreactivity was only found in satellite cells...
  4. Rane S, Reddy E. JAKs, STATs and Src kinases in hematopoiesis. Oncogene. 2002;21:3334-58 pubmed
  5. Lv N, Kim E, Song M, Choi H, Moon W, Park S, et al. JANEX-1, a JAK3 inhibitor, protects pancreatic islets from cytokine toxicity through downregulation of NF-kappaB activation and the JAK/STAT pathway. Exp Cell Res. 2009;315:2064-71 pubmed publisher
    JANEX-1/WHI-P131, a selective Janus kinase 3 (JAK3) inhibitor, has been shown to delay the onset of diabetes in the NOD mouse model. However, the molecular mechanism by which JANEX-1 protects pancreatic beta-cells is unknown...
  6. Bunting K, Sangster M, Ihle J, Sorrentino B. Restoration of lymphocyte function in Janus kinase 3-deficient mice by retroviral-mediated gene transfer. Nat Med. 1998;4:58-64 pubmed
    Janus kinase-3 (JAK3) deficiency has recently been identified as a cause of severe combined immunodeficiency (SCID) in humans. We used a mouse model of Jak3-deficient SCID to test a gene therapy approach for treatment of this disease...
  7. Bixler G, VanGuilder H, Brucklacher R, Kimball S, Bronson S, Freeman W. Chronic insulin treatment of diabetes does not fully normalize alterations in the retinal transcriptome. BMC Med Genomics. 2011;4:40 pubmed publisher
    ..A subset of genes (Ccr5, Jak3, Litaf) was confirmed at the level of protein expression, with protein levels recapitulating changes in mRNA ..
  8. 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. ..
  9. Milici A, Kudlacz E, Audoly L, Zwillich S, Changelian P. Cartilage preservation by inhibition of Janus kinase 3 in two rodent models of rheumatoid arthritis. Arthritis Res Ther. 2008;10:R14 pubmed publisher
    CP-690550 is a small molecule inhibitor of Janus kinase 3 (JAK3), a critical enzyme in the signaling pathway of multiple cytokines (interleukin (IL)-2, -7, -15 and -21) that are important in various T cell functions including development, ..
  10. Bongfen S, Rodrigue Gervais I, Berghout J, Torre S, Cingolani P, Wiltshire S, et al. An N-ethyl-N-nitrosourea (ENU)-induced dominant negative mutation in the JAK3 kinase protects against cerebral malaria. PLoS ONE. 2012;7:e31012 pubmed publisher
    ..genome sequencing as homozygosity for a mis-sense mutation (W81R) in the FERM domain of Janus-associated kinase 3 (Jak3)...
  11. Elliott N, Cleveland S, Grann V, Janik J, Waldmann T, DAVE U. FERM domain mutations induce gain of function in JAK3 in adult T-cell leukemia/lymphoma. Blood. 2011;118:3911-21 pubmed publisher
    ..In this study, we focused on JAK3, the nonreceptor tyrosine kinase that signals from the IL-2R, where activating mutations have been found in diverse ..
  12. Kim B, Kim M, Yin C, Jee J, Sandoval C, Lee H, et al. Inhibition of the signalling kinase JAK3 alleviates inflammation in monoarthritic rats. Br J Pharmacol. 2011;164:106-18 pubmed publisher
    ..cytokines associated with autoimmune disorders and inflammation have been shown to activate the signalling kinase JAK3, implying that JAK3 plays key roles in the pathogenesis of these diseases...
  13. Mahajan S, Hogan J, Shlyakhter D, Oh L, Salituro F, Farmer L, et al. VX-509 (decernotinib) is a potent and selective janus kinase 3 inhibitor that attenuates inflammation in animal models of autoimmune disease. J Pharmacol Exp Ther. 2015;353:405-14 pubmed publisher
    ..A number of these cytokines are critical for lymphocyte development and mediating immune responses. JAK3 is of particular interest due to its importance in immune function and its expression, which is largely confined to ..
  14. 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...
  15. Walters D, Mercher T, Gu T, O Hare T, Tyner J, Loriaux M, et al. Activating alleles of JAK3 in acute megakaryoblastic leukemia. Cancer Cell. 2006;10:65-75 pubmed
    ..This allowed the identification of an activating mutation (A572V) in the JAK3 pseudokinase domain in the acute megakaryoblastic leukemia (AMKL) cell line CMK...
  16. 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...
  17. Eynon E, Livak F, Kuida K, Schatz D, Flavell R. Distinct effects of Jak3 signaling on alphabeta and gammadelta thymocyte development. J Immunol. 1999;162:1448-59 pubmed
    Janus kinase 3 (Jak3) plays a central role in the transduction of signals mediated by the IL-2 family of cytokine receptors...
  18. Murray P. The JAK-STAT signaling pathway: input and output integration. J Immunol. 2007;178:2623-9 pubmed
    ..New data suggests that SOCS proteins introduce additional diversity into the JAK-STAT pathway by adjusting the output of activated STATs that alters downstream gene activation. ..
  19. 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. ..
  20. Uckun F, Roers B, Waurzyniak B, Liu X, Cetkovic Cvrlje M. Janus kinase 3 inhibitor WHI-P131/JANEX-1 prevents graft-versus-host disease but spares the graft-versus-leukemia function of the bone marrow allografts in a murine bone marrow transplantation model. Blood. 2002;99:4192-9 pubmed
    ..present study was to evaluate the effects of graft-versus-host disease (GVHD) prophylaxis with the Janus kinase 3 (JAK3) inhibitor WHI-P131/JANEX-1 on the graft-versus-leukemic (GVL) function of marrow allografts in mice undergoing ..
  21. Saini M, Vaish V, Sanyal S. Role of cytokines and Jak3/Stat3 signaling in the 1,2-dimethylhydrazine dihydrochloride-induced rat model of colon carcinogenesis: early target in the anticancer strategy. Eur J Cancer Prev. 2013;22:215-28 pubmed publisher
    ..IL-1?), IL-2, interferon ?, and tumor necrosis factor-?] and the transcription factors [Janus kinase 3 (Jak3) and signal transducer and activator of transcription 3 (Stat3)] was found in the 1,2-dimethylhydrazine ..
  22. Henkels K, Farkaly T, Mahankali M, Segall J, Gomez Cambronero J. Cell invasion of highly metastatic MTLn3 cancer cells is dependent on phospholipase D2 (PLD2) and Janus kinase 3 (JAK3). J Mol Biol. 2011;408:850-62 pubmed publisher
    ..We also report that PLD2 is under the control of Janus kinase 3 (JAK3), with the kinase phosphorylating PLD2 at the Y415 residue, thus enabling its activation...
  23. Behbod F, Erwin Cohen R, Wang M, Trawick B, Qu X, Verani R, et al. Concomitant inhibition of Janus kinase 3 and calcineurin-dependent signaling pathways synergistically prolongs the survival of rat heart allografts. J Immunol. 2001;166:3724-32 pubmed
    The cytoplasmic localized Janus tyrosine kinase 3 (Jak3) is activated by multiple cytokines, including IL-2, IL-4, and IL-7, through engagement of the IL-2R common gamma-chain...
  24. Moriggl R, Sexl V, Piekorz R, Topham D, Ihle J. Stat5 activation is uniquely associated with cytokine signaling in peripheral T cells. Immunity. 1999;11:225-30 pubmed
    ..Here we demonstrate that activation of the Stat5 proteins by tyrosine phosphorylation is uniquely contributed by cytokine receptor signaling and specifically does not occur through the T cell receptor complex. ..
  25. Stepkowski S, Erwin Cohen R, Behbod F, Wang M, Qu X, Tejpal N, et al. Selective inhibitor of Janus tyrosine kinase 3, PNU156804, prolongs allograft survival and acts synergistically with cyclosporine but additively with rapamycin. Blood. 2002;99:680-9 pubmed
    Janus kinase 3 (Jak3) is a cytoplasmic tyrosine (Tyr) kinase associated with the interleukin-2 (IL-2) receptor common gamma chain (gamma(c)) that is activated by multiple T-cell growth factors (TCGFs) such as IL-2, -4, and -7...
  26. Takahashi T, Shirasawa T. Molecular cloning of rat JAK3, a novel member of the JAK family of protein tyrosine kinases. FEBS Lett. 1994;342:124-8 pubmed
    We have cloned and sequenced a cDNA (JAK3) encoding a novel member of the JAK family of protein tyrosine kinases...
  27. 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...
  28. Orellana D, Quintanilla R, Gonzalez Billault C, Maccioni R. Role of the JAKs/STATs pathway in the intracellular calcium changes induced by interleukin-6 in hippocampal neurons. Neurotox Res. 2005;8:295-304 pubmed
    ..show that this calcium influx is mediated by the JAKs/STATs pathway, since the inhibitor of JAKs/STATs pathway, JAK 3 inhibitor, blocks calcium influx even in the presence of IL-6...
  29. Xu W, Chen M, Ge N, Xu J. Hemagglutinin from the H5N1 virus activates Janus kinase 3 to dysregulate innate immunity. PLoS ONE. 2012;7:e31721 pubmed publisher
    ..signalling in the pulmonary epithelial cells, through an unusual process involving activation of Janus kinase 3 (JAK3) that is exclusively associated with ?c chain and is essential for signaling via all ?c cytokine receptors...
  30. Ban S, Salzer E, Eibl M, Linder A, Geier C, Santos Valente E, et al. Combined immunodeficiency evolving into predominant CD4+ lymphopenia caused by somatic chimerism in JAK3. J Clin Immunol. 2014;34:941-53 pubmed publisher
    ..A novel homozygous missense mutation was revealed in the kinase domain of JAK3 (c.T3196C, p.Cys1066Arg). Further analysis showed revertant chimerism in CD8+ T-cells in both patients...
  31. Kirken R, Rui H, Malabarba M, Farrar W. Identification of interleukin-2 receptor-associated tyrosine kinase p116 as novel leukocyte-specific Janus kinase. J Biol Chem. 1994;269:19136-41 pubmed
    ..However, we identified the IL-2-modulated p116 as the recently cloned novel leukocyte Janus kinase, L-JAK, using an antiserum to a peptide corresponding to the COOH terminus of human L-JAK. ..
  32. Chang K, Lai C, Huang S, Tai H, Chang L, Lin S, et al. Downregulation of Janus kinase 3 expression by small interfering RNA in rat composite tissue allotransplantation. Transpl Immunol. 2009;21:27-32 pubmed publisher
    ..The Janus kinase 3 (JAK3) is also pertinent to the development of a new immuno-suppressant...
  33. Tortolani P, Lal B, Riva A, Johnston J, Chen Y, Reaman G, et al. Regulation of JAK3 expression and activation in human B cells and B cell malignancies. J Immunol. 1995;155:5220-6 pubmed
    ..We have cloned JAK3, which unlike other known family members (JAK1, JAK2, and TYK2) is preferentially expressed in hematopoietic cells ..
  34. Yin L, Chen Y, Qu Z, Zhang L, Wang Q, Zhang Q, et al. Involvement of JAK/STAT signaling in the effect of cornel iridoid glycoside on experimental autoimmune encephalomyelitis amelioration in rats. J Neuroimmunol. 2014;274:28-37 pubmed publisher
    ..Also, CIG treatment inhibited brain JAK/STAT1/3 and reduced proinflammatory cytokines. CIG might be a novel potential therapeutic agent for multiple sclerosis (MS). ..
  35. Degryse S, de Bock C, Cox L, Demeyer S, Gielen O, Mentens N, et al. JAK3 mutants transform hematopoietic cells through JAK1 activation, causing T-cell acute lymphoblastic leukemia in a mouse model. Blood. 2014;124:3092-100 pubmed publisher
    b>JAK3 is a tyrosine kinase that associates with the common γ chain of cytokine receptors and is recurrently mutated in T-cell acute lymphoblastic leukemia (T-ALL)...
  36. Bingisser R, Tilbrook P, Holt P, Kees U. Macrophage-derived nitric oxide regulates T cell activation via reversible disruption of the Jak3/STAT5 signaling pathway. J Immunol. 1998;160:5729-34 pubmed
    ..with specific Abs and subsequent immunoblotting indicated marked reduction of tyrosine phosphorylation of Jak3 and STAT5 mediated by NO...