Jak3

Summary

Gene Symbol: Jak3
Description: Janus kinase 3
Alias: JAK-3, JAK3_HUMAN, JAKL, L-JAK, LJAK, tyrosine-protein kinase JAK3, Janus kinase 3 (a protein tyrosine kinase, leukocyte), leukocyte Janus kinase
Species: human
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. 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. 2017;: 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 ..
  3. 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...
  4. 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
    ..Next-generation sequencing (NGS) of cancer gene panels are widely applied to enable personalized cancer therapy and to identify novel oncogenic mutations...
  5. Recher M, Berglund L, Avery D, Cowan M, Gennery A, Smart J, et al. IL-21 is the primary common γ 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...
  6. 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...
  7. 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 ..
  8. Sheikh A, Hooda O, Dang A. JAK3 and PI3K mediates bovine Interferon-tau stimulated gene expression in the blood neutrophils. J Cell Physiol. 2017;: 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 hour duration...
  9. 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 ..
  10. Robinette M, Cella M, Telliez J, Ulland T, Barrow A, Capuder K, et al. Jak3 deficiency blocks innate lymphoid cell development. Mucosal Immunol. 2017;: pubmed publisher
    Loss-of-function mutations in the tyrosine kinase JAK3 cause autosomal recessive severe combined immunodeficiency (SCID)...

Detail Information

Publications62

  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. 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. 2017;: 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 ..
  3. 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...
  4. 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
    ..Next-generation sequencing (NGS) of cancer gene panels are widely applied to enable personalized cancer therapy and to identify novel oncogenic mutations...
  5. Recher M, Berglund L, Avery D, Cowan M, Gennery A, Smart J, et al. IL-21 is the primary common γ 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...
  6. 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...
  7. 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 ..
  8. Sheikh A, Hooda O, Dang A. JAK3 and PI3K mediates bovine Interferon-tau stimulated gene expression in the blood neutrophils. J Cell Physiol. 2017;: 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 hour duration...
  9. 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 ..
  10. Robinette M, Cella M, Telliez J, Ulland T, Barrow A, Capuder K, et al. Jak3 deficiency blocks innate lymphoid cell development. Mucosal Immunol. 2017;: pubmed publisher
    Loss-of-function mutations in the tyrosine kinase JAK3 cause autosomal recessive severe combined immunodeficiency (SCID)...
  11. 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...
  12. 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...
  13. 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-β expression by FXR deficiency impaired the downstream JAK3-STAT1 signaling pathways, which in turn increased osteoclast formation...
  14. 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...
  15. 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...
  16. 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. 2017;: pubmed publisher
    The BTK and JAK3 receptor tyrosine kinases are two validated and therapeutically amenable targets in the treatment of B-cell lymphomas...
  17. Notarangelo L, Mella P, Jones A, de Saint Basile G, Savoldi G, Cranston T, et al. Mutations in severe combined immune deficiency (SCID) due to JAK3 deficiency. Hum Mutat. 2001;18:255-63 pubmed
    ..Among them is the JAK3-gene, encoding for a tyrosine kinase that is functionally coupled to cytokine receptors which share the common ..
  18. Changelian P, Flanagan M, Ball D, Kent C, Magnuson K, Martin W, et al. Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor. Science. 2003;302:875-8 pubmed
    Because of its requirement for signaling by multiple cytokines, Janus kinase 3 (JAK3) is an excellent target for clinical immunosuppression...
  19. 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...
  20. Mori D, Nakafusa Y, Miyazaki K, Tokunaga O. Differential expression of Janus kinase 3 (JAK3), matrix metalloproteinase 13 (MMP13), heat shock protein 60 (HSP60), and mouse double minute 2 (MDM2) in human colorectal cancer progression using human cancer cDNA microarrays. Pathol Res Pract. 2005;201:777-89 pubmed
    ..we immunohistochemically investigated the expression of the four top ranked upregulated genes, Janus kinase 3 (JAK3), matrix metalloproteinase 13 (MMP13), heat shock protein 60 (HSP60), and mouse double minute 2 (MDM2), in 44 CRC...
  21. Chen X, Ji N, Qin N, Tang S, Wang R, Qiu Y, et al. 1,6-O,O-Diacetylbritannilactone Inhibits Eotaxin-1 and ALOX15 Expression Through Inactivation of STAT6 in A549 Cells. Inflammation. 2017;40:1967-1974 pubmed publisher
    ..Furthermore, OODBL suppressed phosphorylation of Janus Kinase 3 (JAK3) without affecting JAK1...
  22. Shi M, Lin T, Appell K, Berg L. Cell cycle progression following naive T cell activation is independent of Jak3/common gamma-chain cytokine signals. J Immunol. 2009;183:4493-501 pubmed publisher
    ..In this report, we examine in detail the role of Jak3/common gamma-chain-dependent cytokines in promoting cell cycle progression and proliferation of naive T cells...
  23. Wang Y, Huang W, Xin M, Chen P, Gui L, Zhao X, et al. Identification of 4-(2-furanyl)pyrimidin-2-amines as Janus kinase 2 inhibitors. Bioorg Med Chem. 2017;25:75-83 pubmed publisher
    ..Primary SAR studies resulted in the discovery of a novel class of 4,5,6,7-tetrahydrofuro[3,2-c]pyridine based JAK2 inhibitors with higher potency (IC50 of 0.7nM) and selectivity (>30 fold) to JAK3 kinase than tofacitinib.
  24. Cattaneo F, Recher M, Masneri S, Baxi S, Fiorini C, Antonelli F, et al. Hypomorphic Janus kinase 3 mutations result in a spectrum of immune defects, including partial maternal T-cell engraftment. J Allergy Clin Immunol. 2013;131:1136-45 pubmed publisher
    Mutations in Janus kinase 3 (JAK3) are a cause of severe combined immunodeficiency, but hypomorphic JAK3 defects can result in a milder clinical phenotype, with residual development and function of autologous T cells...
  25. Huang K, Wang Y, Zhang T, He M, Sun G, Wen J, et al. JAK signaling regulates germline cyst breakdown and primordial follicle formation in mice. Biol Open. 2017;: pubmed publisher
    ..JAK) signaling is vital for germline cyst breakdown and primordial follicle formation in vitro JAK2 and JAK3 activity is increased while germline cysts are breaking down...
  26. Aringer M, Hofmann S, Frucht D, Chen M, Centola M, Morinobu A, et al. Characterization and analysis of the proximal Janus kinase 3 promoter. J Immunol. 2003;170:6057-64 pubmed
    Janus kinase 3 (Jak3) is a nonreceptor tyrosine kinase essential for signaling via cytokine receptors that comprise the common gamma-chain (gammac), i.e., the receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21...
  27. 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.
  28. Johnston J, Wang L, Hanson E, Sun X, White M, Oakes S, et al. Interleukins 2, 4, 7, and 15 stimulate tyrosine phosphorylation of insulin receptor substrates 1 and 2 in T cells. Potential role of JAK kinases. J Biol Chem. 1995;270:28527-30 pubmed
    ..In addition, we show that the Janus kinases, JAK1 and JAK3, associate with IRS-1 and IRS-2 in T cells...
  29. Yang Y, Ding L, Hu Q, Xia J, Sun J, Wang X, et al. MicroRNA-218 functions as a tumor suppressor in lung cancer by targeting IL-6/STAT3 and negatively correlates with poor prognosis. Mol Cancer. 2017;16:141 pubmed publisher
    ..Levels of miR-218, IL-6R, JAK3 and phosphorylated STAT3 were compared in ALDH1A1 positive and ALDH1A1 negative cells...
  30. Choi Y, Kaneda R, Wada T, Fujiwara S, Soda M, Watanabe H, et al. Identification of a constitutively active mutant of JAK3 by retroviral expression screening. Leuk Res. 2007;31:203-9 pubmed
    ..of the cell clones which proliferated in the presence of granulocyte colony-stimulating factor were derived from JAK3 encoding a JAK3 mutant with a valine-to-alanine substitution at codon 674 and two additional amino acid ..
  31. Henkels K, Frondorf K, Gonzalez Mejia M, Doseff A, Gomez Cambronero J. IL-8-induced neutrophil chemotaxis is mediated by Janus kinase 3 (JAK3). FEBS Lett. 2011;585:159-66 pubmed publisher
    Janus kinase 3 (JAK3) is a non-receptor tyrosine kinase vital to the regulation of T-cells. We report that JAK3 is a mediator of interleukin-8 (IL-8) stimulation of a different class of hematopoietic relevant cells: human neutrophils...
  32. Sanchez Margalet V, Martin Romero C. Human leptin signaling in human peripheral blood mononuclear cells: activation of the JAK-STAT pathway. Cell Immunol. 2001;211:30-6 pubmed
    ..This pathway may mediate, at least in part, the action of human leptin in human peripheral blood mononuclear cells. ..
  33. Krejsgaard T, Vetter Kauczok C, Woetmann A, Lovato P, Labuda T, Eriksen K, et al. Jak3- and JNK-dependent vascular endothelial growth factor expression in cutaneous T-cell lymphoma. Leukemia. 2006;20:1759-66 pubmed
    ..Moreover, the VEGF production is associated with constitutive activity of Janus kinase 3 (Jak3) and the c-Jun N-terminal kinases (JNKs)...
  34. Qamar F, Junejo S, Qureshi S, Seleman M, Bainter W, Massaad M, et al. A novel mutation in the JH4 domain of JAK3 causing severe combined immunodeficiency complicated by vertebral osteomyelitis. Clin Immunol. 2017;183:198-200 pubmed publisher
    b>JAK3 is a tyrosine kinase essential for signaling downstream of the common gamma chain subunit shared by multiple cytokine receptors...
  35. Musso T, Johnston J, Linnekin D, Varesio L, Rowe T, O Shea J, et al. Regulation of JAK3 expression in human monocytes: phosphorylation in response to interleukins 2, 4, and 7. J Exp Med. 1995;181:1425-31 pubmed
    ..Recently, we have cloned a novel JAK family member, JAK3, that is expressed in natural killer and activated T cells and is coupled functionally and physically to the ..
  36. Sharfe N, Dadi H, Roifman C. JAK3 protein tyrosine kinase mediates interleukin-7-induced activation of phosphatidylinositol-3' kinase. Blood. 1995;86:2077-85 pubmed
    ..We have identified IL-7-induced activation of three cyoplasmic tyrosine kinases in T cells, Jak1, Jak3, and the src-like kinase p56lck...
  37. 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...
  38. Riedy M, Dutra A, Blake T, Modi W, Lal B, Davis J, et al. Genomic sequence, organization, and chromosomal localization of human JAK3. Genomics. 1996;37:57-61 pubmed
    Members of the Janus (JAK) protein tyrosine kinase family including JAK3 have recently emerged as important components in cytokine signal transduction...
  39. 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 ..
  40. Silva P, Nelson C, Driver J, Thatcher W, Chebel R. Effect of recombinant bovine somatotropin on leukocyte mRNA expression for genes related to cell energy metabolism, cytokine production, phagocytosis, oxidative burst, and adaptive immunity. J Dairy Sci. 2017;100:8471-8483 pubmed publisher
    ..of mRNA for STAT1, RELA, and NOD2 tended to be upregulated, expression of RAC2 was downregulated, and expression of JAK3, BLK, and TNFα tended to be downregulated on d 7 relative to calving by rbST treatment...
  41. Springuel L, Losdyck E, Saussoy P, Turcq B, Mahon F, Knoops L, et al. Loss of mutL homolog-1 (MLH1) expression promotes acquisition of oncogenic and inhibitor-resistant point mutations in tyrosine kinases. Cell Mol Life Sci. 2016;73:4739-4748 pubmed
    ..reported that the IL-9-dependent TS1 cell line sequentially acquired activating substitutions in JAK1 and JAK3 upon successive selections for growth factor independent and JAK inhibitor-resistant cells, suggestive of a defect ..
  42. Doucet C, Giron Michel J, Canonica G, Azzarone B. Human lung myofibroblasts as effectors of the inflammatory process: the common receptor gamma chain is induced by Th2 cytokines, and CD40 ligand is induced by lipopolysaccharide, thrombin and TNF-alpha. Eur J Immunol. 2002;32:2437-49 pubmed
    ..JAK) 3, while lung myofibroblasts constitutively express a gamma c chain displaying a limited association with JAK3. In the latter cells, without exogenous cytokines, gamma c/JAK3 controls, through autocrine loops, tyrosine kinase (..
  43. Sumitomo S, Nagafuchi Y, Tsuchida Y, Tsuchiya H, Ota M, Ishigaki K, et al. A gene module associated with dysregulated TCR signaling pathways in CD4+ T cell subsets in rheumatoid arthritis. J Autoimmun. 2017;: pubmed publisher
    ..91, p = 5 × 10-57). The most highly connected 30 genes of this module included ZAP70 and JAK3, and pathway analysis of this module revealed dysregulation of the TCR signaling pathway network, which was ..
  44. Lindholm C. IL-2 receptor signaling through the Shb adapter protein in T and NK cells. Biochem Biophys Res Commun. 2002;296:929-36 pubmed
    ..JAK1 and JAK3 were also found to associate with Shb, but in contrast to the Shb-IL-2 receptor association, JAK1 and 3 appear to ..
  45. Hoffman S, Lai K, Tomfohrde J, Bowcock A, Gordon L, Mohrenweiser H. JAK3 maps to human chromosome 19p12 within a cluster of proto-oncogenes and transcription factors. Genomics. 1997;43:109-11 pubmed
  46. Kalman L, Lindegren M, Kobrynski L, Vogt R, Hannon H, Howard J, et al. Mutations in genes required for T-cell development: IL7R, CD45, IL2RG, JAK3, RAG1, RAG2, ARTEMIS, and ADA and severe combined immunodeficiency: HuGE review. Genet Med. 2004;6:16-26 pubmed
    ..Mutations in any of eight known genes: IL2RG, ARTEMIS, RAG1, RAG2, ADA, CD45, JAK3, and IL7R cause SCID. Mutations in unidentified genes may also cause SCID...
  47. Cornejo M, Kharas M, Werneck M, Le Bras S, Moore S, Ball B, et al. Constitutive JAK3 activation induces lymphoproliferative syndromes in murine bone marrow transplantation models. Blood. 2009;113:2746-54 pubmed publisher
    The tyrosine kinase JAK3 plays a well-established role during normal lymphocyte development and is constitutively phosphorylated in several lymphoid malignancies. However, its contribution to lymphomagenesis remains elusive...