Janus kinase 3
Tyrosine-protein kinase JAK3 is an enzyme that in humans is encoded by the JAK3 gene.[1][2]
JAK3 encodes Janus kinase 3, a tyrosine kinase that belongs to the Janus family. JAK3 functions in signal transduction and interacts with members of the STAT (signal transduction and activators of transcription) family. JAK3 is predominantly expressed in immune cells and transduces a signal in response to its activation via tyrosine phosphorylation by interleukin receptors. Mutations that abrogate Janus kinase 3 function cause an autosomal SCID (severe combined immunodeficiency disease).[3]
Since JAK3 expression is restricted mostly to hematopoietic cells, its role in cytokine signaling is thought to be more restricted than other JAKs. It is most commonly expressed in T cells and NK cells, but has been induced in other leukocytes, including monocytes. Jak3 is involved in signal transduction by receptors that employ the common gamma chain (γC) of the type I cytokine receptor family (e.g. IL-2R, IL-4R, IL-7R, IL-9R, IL-15R, and IL-21R).[4] Mutations of JAK3 result in severe combined immunodeficiency (SCID). Mice that do not express JAK3 have T-cells and B-cells that fail to respond to many cytokines.[5]
Interactions
Janus kinase 3 has been shown to interact with CD247,[6] TIAF1[7] and IL2RG.[8][9]
References
- ^ Riedy MC, Dutra AS, Blake TB, Modi W, Lal BK, Davis J, Bosse A, O'Shea JJ, Johnston JA (Feb 1997). "Genomic sequence, organization, and chromosomal localization of human JAK3". Genomics 37 (1): 57–61. doi:10.1006/geno.1996.0520. PMID 8921370.
- ^ Hoffman SM, Lai KS, Tomfohrde J, Bowcock A, Gordon LA, Mohrenweiser HW (Sep 1997). "JAK3 maps to human chromosome 19p12 within a cluster of proto-oncogenes and transcription factors". Genomics 43 (1): 109–11. doi:10.1006/geno.1997.4792. PMID 9226382.
- ^ "Entrez Gene: JAK3 Janus kinase 3 (a protein tyrosine kinase, leukocyte)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3718.
- ^ Johnston JA, Kawamura M, Kirken RA, Chen YQ, Blake TB, Shibuya K, Ortaldo JR, McVicar DW, O'Shea JJ. (1994). "Phosphorylation and activation of the Jak-3 Janus kinase in response to interleukin-2". Nature 370 (6485): 151–153. doi:10.1038/370151a0. PMID 8022485.
- ^ Fujimoto M, Naka T, Nakagawa R, Kawazoe Y, Morita Y, Tateishi A, Okumura K, Narazaki M, Kishimoto T (2000). "Defective thymocyte development and perturbed homeostasis of T cells in STAT-induced STAT inhibitor-1/suppressors of cytokine signaling-1 transgenic mice". J. Immunol. 165 (4): 1799–806. PMID 10925257.
- ^ Tomita, K; Saijo K, Yamasaki S, Iida T, Nakatsu F, Arase H, Ohno H, Shirasawa T, Kuriyama T, O'Shea J J, Saito T (Jul. 2001). "Cytokine-independent Jak3 activation upon T cell receptor (TCR) stimulation through direct association of Jak3 and the TCR complex". J. Biol. Chem. (United States) 276 (27): 25378–85. doi:10.1074/jbc.M011363200. ISSN 0021-9258. PMID 11349123.
- ^ Ji, H; Zhai Q, Zhu J, Yan M, Sun L, Liu X, Zheng Z (Apr. 2000). "A novel protein MAJN binds to Jak3 and inhibits apoptosis induced by IL-2 deprival". Biochem. Biophys. Res. Commun. (UNITED STATES) 270 (1): 267–71. doi:10.1006/bbrc.2000.2413. ISSN 0006-291X. PMID 10733938.
- ^ Miyazaki, T; Kawahara A, Fujii H, Nakagawa Y, Minami Y, Liu Z J, Oishi I, Silvennoinen O, Witthuhn B A, Ihle J N (Nov. 1994). "Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits". Science (UNITED STATES) 266 (5187): 1045–7. doi:10.1126/science.7973659. ISSN 0036-8075. PMID 7973659.
- ^ Russell, S M; Johnston J A, Noguchi M, Kawamura M, Bacon C M, Friedmann M, Berg M, McVicar D W, Witthuhn B A, Silvennoinen O (Nov. 1994). "Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID". Science (UNITED STATES) 266 (5187): 1042–5. doi:10.1126/science.7973658. ISSN 0036-8075. PMID 7973658.
Further reading
- Notarangelo LD, Mella P, Jones A et al. (2002). "Mutations in severe combined immune deficiency (SCID) due to JAK3 deficiency". Hum. Mutat. 18 (4): 255–63. doi:10.1002/humu.1188. PMID 11668610.
- Russell SM, Tayebi N, Nakajima H et al. (1995). "Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development". Science 270 (5237): 797–800. doi:10.1126/science.270.5237.797. PMID 7481768.
- Johnston JA, Wang LM, Hanson EP et al. (1996). "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. 270 (48): 28527–30. doi:10.1074/jbc.270.48.28527. PMID 7499365.
- Musso T, Johnston JA, Linnekin D et al. (1995). "Regulation of JAK3 expression in human monocytes: phosphorylation in response to interleukins 2, 4, and 7". J. Exp. Med. 181 (4): 1425–31. doi:10.1084/jem.181.4.1425. PMC 2191962. PMID 7535338. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2191962.
- Rolling C, Treton D, Beckmann P et al. (1995). "JAK3 associates with the human interleukin 4 receptor and is tyrosine phosphorylated following receptor triggering". Oncogene 10 (9): 1757–61. PMID 7538655.
- Lai KS, Jin Y, Graham DK et al. (1995). "A kinase-deficient splice variant of the human JAK3 is expressed in hematopoietic and epithelial cancer cells". J. Biol. Chem. 270 (42): 25028–36. doi:10.1074/jbc.270.42.25028. PMID 7559633.
- Macchi P, Villa A, Giliani S et al. (1995). "Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID)". Nature 377 (6544): 65–8. doi:10.1038/377065a0. PMID 7659163.
- Russell SM, Johnston JA, Noguchi M et al. (1994). "Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID". Science 266 (5187): 1042–5. doi:10.1126/science.7973658. PMID 7973658.
- Miyazaki T, Kawahara A, Fujii H et al. (1994). "Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits". Science 266 (5187): 1045–7. doi:10.1126/science.7973659. PMID 7973659.
- Johnston JA, Kawamura M, Kirken RA et al. (1994). "Phosphorylation and activation of the Jak-3 Janus kinase in response to interleukin-2". Nature 370 (6485): 151–3. doi:10.1038/370151a0. PMID 8022485.
- Witthuhn BA, Silvennoinen O, Miura O et al. (1994). "Involvement of the Jak-3 Janus kinase in signalling by interleukins 2 and 4 in lymphoid and myeloid cells". Nature 370 (6485): 153–7. doi:10.1038/370153a0. PMID 8022486.
- Kawamura M, McVicar DW, Johnston JA et al. (1994). "Molecular cloning of L-JAK, a Janus family protein-tyrosine kinase expressed in natural killer cells and activated leukocytes". Proc. Natl. Acad. Sci. U.S.A. 91 (14): 6374–8. doi:10.1073/pnas.91.14.6374. PMC 44204. PMID 8022790. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=44204.
- Verbsky JW, Bach EA, Fang YF et al. (1996). "Expression of Janus kinase 3 in human endothelial and other non-lymphoid and non-myeloid cells". J. Biol. Chem. 271 (24): 13976–80. doi:10.1074/jbc.271.24.13976. PMID 8662778.
- Fusaki N, Iwamatsu A, Iwashima M, Fujisawa J (1997). "Interaction between Sam68 and Src family tyrosine kinases, Fyn and Lck, in T cell receptor signaling". J. Biol. Chem. 272 (10): 6214–9. doi:10.1074/jbc.272.10.6214. PMID 9045636.
- Fujitani Y, Hibi M, Fukada T et al. (1997). "An alternative pathway for STAT activation that is mediated by the direct interaction between JAK and STAT". Oncogene 14 (7): 751–61. doi:10.1038/sj.onc.1200907. PMID 9047382.
- Safford MG, Levenstein M, Tsifrina E et al. (1997). "JAK3: expression and mapping to chromosome 19p12-13.1". Exp. Hematol. 25 (5): 374–86. PMID 9168059.
- Sharfe N, Dadi HK, O'Shea JJ, Roifman CM (1997). "Jak3 activation in human lymphocyte precursor cells". Clin. Exp. Immunol. 108 (3): 552–6. doi:10.1046/j.1365-2249.1997.4001304.x. PMC 1904698. PMID 9182906. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1904698.
- Candotti F, Oakes SA, Johnston JA et al. (1997). "Structural and functional basis for JAK3-deficient severe combined immunodeficiency". Blood 90 (10): 3996–4003. PMID 9354668.
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PDB gallery
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1yvj: Crystal structure of the Jak3 kinase domain in complex with a staurosporine analogue
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External links
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SRC-A family
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SRC-B family
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B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6
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| Ligand |
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| Cytokine receptor |
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| Janus kinase |
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| Adaptor proteins |
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B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
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