Janus kinase 1

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Janus kinase 1
Protein JAK1 PDB 3EYG.png
Rendering based on PDB 3EYG.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols JAK1 ; JAK1A; JAK1B; JTK3
External IDs OMIM147795 MGI96628 HomoloGene1678 ChEMBL: 2835 GeneCards: JAK1 Gene
EC number
RNA expression pattern
PBB GE JAK1 201648 at tn.png
More reference expression data
Species Human Mouse
Entrez 3716 16451
Ensembl ENSG00000162434 ENSMUSG00000028530
UniProt P23458 B1ASP2
RefSeq (mRNA) NM_002227 NM_146145
RefSeq (protein) NP_002218 NP_666257
Location (UCSC) Chr 1:
65.3 – 65.43 Mb
Chr 4:
101.15 – 101.27 Mb
PubMed search [1] [2]

JAK1 is a human tyrosine kinase protein essential for signaling for certain type I and type II cytokines. It interacts with the common gamma chain (γc) of type I cytokine receptors, to elicit signals from the IL-2 receptor family (e.g. IL-2R, IL-7R, IL-9R and IL-15R), the IL-4 receptor family (e.g. IL-4R and IL-13R), the gp130 receptor family (e.g. IL-6R, IL-11R, LIF-R, OSM-R, cardiotrophin-1 receptor (CT-1R), ciliary neurotrophic factor receptor (CNTF-R), neurotrophin-1 receptor (NNT-1R) and Leptin-R). It is also important for transducing a signal by type I (IFN-α/β) and type II (IFN-γ) interferons, and members of the IL-10 family via type II cytokine receptors.[1] Jak1 plays a critical role in initiating responses to multiple major cytokine receptor families. Loss of Jak1 is lethal in neonatal mice, possibly due to difficulties suckling.[2] Expression of JAK1 in cancer cells enables individual cells to contract, potentially allowing them to escape their tumor and metastasize to other parts of the body.[3]


Janus kinase 1 has been shown to interact with PTPN11,[4][5] Glycoprotein 130,[6][7][8] Interleukin 10 receptor, alpha subunit,[9][10] ELP2,[11] STAT3,[12][13] Grb2,[14][15] STAT5A,[16] STAT5B,[16] IL2RB,[10][17][18][19][20] TNFRSF1A,[21][22] IRS1,[23][24] GNB2L1[25] and STAM2.[26][27]


  1. ^ Gadina M, Hilton D, Johnston JA, Morinobu A, Lighvani A, Zhou YJ, Visconti R, O'Shea JJ (2001). "Signaling by type I and II cytokine receptors: ten years after". Curr. Opin. Immunol. 13 (3): 363–73. doi:10.1016/S0952-7915(00)00228-4. PMID 11406370. 
  2. ^ Rodig SJ, Meraz MA, White JM, Lampe PA, Riley JK, Arthur CD, King KL, Sheehan KC, Yin L, Pennica D, Johnson EM, Schreiber RD (1998). "Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses". Cell 93 (3): 373–83. doi:10.1016/S0092-8674(00)81166-6. PMID 9590172. 
  3. ^ Christian Nordqvist. "Protein JAK Makes Cancer Cells Contract, So They Can Squeeze Out Of A Tumor". Medical News Today. 
  4. ^ Yin, T; Shen R; Feng G S; Yang Y C (January 1997). "Molecular characterization of specific interactions between SHP-2 phosphatase and JAK tyrosine kinases". J. Biol. Chem. (UNITED STATES) 272 (2): 1032–7. doi:10.1074/jbc.272.2.1032. ISSN 0021-9258. PMID 8995399. 
  5. ^ Lehmann, Ute; Schmitz Jochen, Weissenbach Manuela, Sobota Radoslaw M, Hortner Michael, Friederichs Kerstin, Behrmann Iris, Tsiaris William, Sasaki Atsuo, Schneider-Mergener Jens, Yoshimura Akihiko, Neel Benjamin G, Heinrich Peter C, Schaper Fred (January 2003). "SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gp130". J. Biol. Chem. (United States) 278 (1): 661–71. doi:10.1074/jbc.M210552200. ISSN 0021-9258. PMID 12403768. 
  6. ^ Haan, C; Is'harc H, Hermanns H M, Schmitz-Van De Leur H, Kerr I M, Heinrich P C, Grötzinger J, Behrmann I (October 2001). "Mapping of a region within the N terminus of Jak1 involved in cytokine receptor interaction". J. Biol. Chem. (United States) 276 (40): 37451–8. doi:10.1074/jbc.M106135200. ISSN 0021-9258. PMID 11468294. 
  7. ^ Kim, H; Baumann H (December 1997). "Transmembrane domain of gp130 contributes to intracellular signal transduction in hepatic cells". J. Biol. Chem. (UNITED STATES) 272 (49): 30741–7. doi:10.1074/jbc.272.49.30741. ISSN 0021-9258. PMID 9388212. 
  8. ^ Haan, Claude; Heinrich Peter C; Behrmann Iris (January 2002). "Structural requirements of the interleukin-6 signal transducer gp130 for its interaction with Janus kinase 1: the receptor is crucial for kinase activation". Biochem. J. (England) 361 (Pt 1): 105–11. doi:10.1042/0264-6021:3610105. ISSN 0264-6021. PMC 1222284. PMID 11742534. 
  9. ^ Usacheva, Anna; Sandoval Raudel; Domanski Paul; Kotenko Sergei V; Nelms Keats; Goldsmith Mark A; Colamonici Oscar R (December 2002). "Contribution of the Box 1 and Box 2 motifs of cytokine receptors to Jak1 association and activation". J. Biol. Chem. (United States) 277 (50): 48220–6. doi:10.1074/jbc.M205757200. ISSN 0021-9258. PMID 12374810. 
  10. ^ a b Usacheva, Anna; Kotenko Sergei; Witte Michael M; Colamonici Oscar R (August 2002). "Two distinct domains within the N-terminal region of Janus kinase 1 interact with cytokine receptors". J. Immunol. (United States) 169 (3): 1302–8. doi:10.4049/jimmunol.169.3.1302. ISSN 0022-1767. PMID 12133952. 
  11. ^ Collum, R G; Brutsaert S; Lee G; Schindler C (August 2000). "A Stat3-interacting protein (StIP1) regulates cytokine signal transduction". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 97 (18): 10120–5. doi:10.1073/pnas.170192197. ISSN 0027-8424. PMC 27739. PMID 10954736. 
  12. ^ Ueda, Takeshi; Bruchovsky Nicholas; Sadar Marianne D (March 2002). "Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways". J. Biol. Chem. (United States) 277 (9): 7076–85. doi:10.1074/jbc.M108255200. ISSN 0021-9258. PMID 11751884. 
  13. ^ Spiekermann, K; Biethahn S; Wilde S; Hiddemann W; Alves F (August 2001). "Constitutive activation of STAT transcription factors in acute myelogenous leukemia". Eur. J. Haematol. (Denmark) 67 (2): 63–71. doi:10.1034/j.1600-0609.2001.t01-1-00385.x. ISSN 0902-4441. PMID 11722592. 
  14. ^ Kim, H; Lee Y H; Won J; Yun Y (September 2001). "Through induction of juxtaposition and tyrosine kinase activity of Jak1, X-gene product of hepatitis B virus stimulates Ras and the transcriptional activation through AP-1, NF-kappaB, and SRE enhancers". Biochem. Biophys. Res. Commun. (United States) 286 (5): 886–94. doi:10.1006/bbrc.2001.5496. ISSN 0006-291X. PMID 11527382. 
  15. ^ Giorgetti-Peraldi, S; Peyrade F; Baron V; Van Obberghen E (December 1995). "Involvement of Janus kinases in the insulin signaling pathway". Eur. J. Biochem. (GERMANY) 234 (2): 656–60. doi:10.1111/j.1432-1033.1995.656_b.x. ISSN 0014-2956. PMID 8536716. 
  16. ^ a b Fujitani, Y; Hibi M, Fukada T, Takahashi-Tezuka M, Yoshida H, Yamaguchi T, Sugiyama K, Yamanaka Y, Nakajima K, Hirano T (February 1997). "An alternative pathway for STAT activation that is mediated by the direct interaction between JAK and STAT". Oncogene (ENGLAND) 14 (7): 751–61. doi:10.1038/sj.onc.1200907. ISSN 0950-9232. PMID 9047382. 
  17. ^ Miyazaki, T; Kawahara A; Fujii H; Nakagawa Y; Minami Y; Liu Z J; Oishi I; Silvennoinen O; Witthuhn B A; Ihle J N (November 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. 
  18. ^ 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 (November 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. 
  19. ^ Zhu, M H; Berry J A; Russell S M; Leonard W J (April 1998). "Delineation of the regions of interleukin-2 (IL-2) receptor beta chain important for association of Jak1 and Jak3. Jak1-independent functional recruitment of Jak3 to Il-2Rbeta". J. Biol. Chem. (UNITED STATES) 273 (17): 10719–25. doi:10.1074/jbc.273.17.10719. ISSN 0021-9258. PMID 9553136. 
  20. ^ Migone, T S; Rodig S; Cacalano N A; Berg M; Schreiber R D; Leonard W J (November 1998). "Functional Cooperation of the Interleukin-2 Receptor β Chain and Jak1 in Phosphatidylinositol 3-Kinase Recruitment and Phosphorylation". Mol. Cell. Biol. (UNITED STATES) 18 (11): 6416–22. ISSN 0270-7306. PMC 109227. PMID 9774657. 
  21. ^ Guo, D; Dunbar J D; Yang C H; Pfeffer L M; Donner D B (March 1998). "Induction of Jak/STAT signaling by activation of the type 1 TNF receptor". J. Immunol. (UNITED STATES) 160 (6): 2742–50. ISSN 0022-1767. PMID 9510175. 
  22. ^ Miscia, Sebastiano; Marchisio Marco; Grilli Alfredo; Di Valerio Valentina; Centurione Lucia; Sabatino Giuseppe; Garaci Francesco; Zauli Giorgio; Bonvini Ezio; Di Baldassarre Angela (January 2002). "Tumor necrosis factor alpha (TNF-alpha) activates Jak1/Stat3-Stat5B signaling through TNFR-1 in human B cells". Cell Growth Differ. (United States) 13 (1): 13–8. ISSN 1044-9523. PMID 11801527. 
  23. ^ Gual, P; Baron V; Lequoy V; Van Obberghen E (March 1998). "Interaction of Janus kinases JAK-1 and JAK-2 with the insulin receptor and the insulin-like growth factor-1 receptor". Endocrinology (UNITED STATES) 139 (3): 884–93. doi:10.1210/en.139.3.884. ISSN 0013-7227. PMID 9492017. 
  24. ^ Johnston, J A; Wang L M, Hanson E P, Sun X J, White M F, Oakes S A, Pierce J H, O'Shea J J (December 1995). "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. (UNITED STATES) 270 (48): 28527–30. doi:10.1074/jbc.270.48.28527. ISSN 0021-9258. PMID 7499365. 
  25. ^ Usacheva, Anna; Tian Xinyong; Sandoval Raudel; Salvi Debra; Levy David; Colamonici Oscar R (September 2003). "The WD motif-containing protein RACK-1 functions as a scaffold protein within the type I IFN receptor-signaling complex". J. Immunol. (United States) 171 (6): 2989–94. doi:10.4049/jimmunol.171.6.2989. ISSN 0022-1767. PMID 12960323. 
  26. ^ Pandey, A; Fernandez M M; Steen H; Blagoev B; Nielsen M M; Roche S; Mann M; Lodish H F (December 2000). "Identification of a novel immunoreceptor tyrosine-based activation motif-containing molecule, STAM2, by mass spectrometry and its involvement in growth factor and cytokine receptor signaling pathways". J. Biol. Chem. (UNITED STATES) 275 (49): 38633–9. doi:10.1074/jbc.M007849200. ISSN 0021-9258. PMID 10993906. 
  27. ^ Endo, K; Takeshita T, Kasai H, Sasaki Y, Tanaka N, Asao H, Kikuchi K, Yamada M, Chenb M, O'Shea J J, Sugamura K (July 2000). "STAM2, a new member of the STAM family, binding to the Janus kinases". FEBS Lett. (NETHERLANDS) 477 (1–2): 55–61. doi:10.1016/S0014-5793(00)01760-9. ISSN 0014-5793. PMID 10899310. 

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