Janus kinase 1 Mammalian protein found in Homo sapiens
JAK1 Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3EYG , 3EYH , 4E4L , 4E4N , 4E5W , 4EHZ , 4EI4 , 4FK6 , 4I5C , 4IVB , 4IVC , 4IVD , 4K6Z , 4K77 , 4L00 , 4L01 , 5E1E , 5HX8 , 5IXD , 5IXI
Identifiers Aliases JAK1 External IDs OMIM : 147795 ; MGI : 96628 ; HomoloGene : 1678 ; GeneCards : JAK1 ; OMA :JAK1 - orthologs Wikidata
Janus kinase 1 (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 .[ 5] [ 6] metastasize to other parts of the body.[ 7]
Interactions
Janus kinase 1 has been shown to interact with:
ELP2 ,[ 8] GNB2L1 [ 9] IL6ST ,[ 10] [ 11] [ 12] Grb2 ,[ 13] [ 14] IL2RB ,[ 15] [ 16] [ 17] [ 18] [ 19] IRS1 ,[ 20] [ 21] IL10RA ,[ 15] [ 22] PTPN11 ,[ 23] [ 24] STAM2 ,[ 25] [ 26] STAT3 ,[ 27] [ 28] STAT5A ,[ 29] STAT5B ,[ 29] TNFRSF1A .[ 30] [ 31]
References
1 2 3 GRCh38: Ensembl release 89: ENSG00000162434 – Ensembl , May 20171 2 3 GRCm38: Ensembl release 89: ENSMUSG00000028530 – Ensembl , May 2017↑ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .↑ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .↑ Gadina M, Hilton D, Johnston JA, Morinobu A, Lighvani A, Zhou YJ, et al. (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 . ↑ Rodig SJ, Meraz MA, White JM, Lampe PA, Riley JK, Arthur CD, et al. (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 . S2CID 18684846 . ↑ Christian Nordqvist. "Protein JAK Makes Cancer Cells Contract, So They Can Squeeze Out Of A Tumor" . Medical News Today . ↑ Collum RG, Brutsaert S, Lee G, Schindler C (August 2000). "A Stat3-interacting protein (StIP1) regulates cytokine signal transduction" . Proc. Natl. Acad. Sci. U.S.A . 97 (18): 10120– 5. Bibcode :2000PNAS...9710120C . doi :10.1073/pnas.170192197 PMC 27739 PMID 10954736 . ↑ Usacheva A, Tian X, Sandoval R, Salvi D, Levy D, Colamonici OR (September 2003). "The WD motif-containing protein RACK-1 functions as a scaffold protein within the type I IFN receptor-signaling complex" . J. Immunol . 171 (6): 2989– 94. doi :10.4049/jimmunol.171.6.2989 PMID 12960323 . ↑ Haan C, Is'harc H, Hermanns HM, Schmitz-Van De Leur H, Kerr IM, Heinrich PC, et al. (October 2001). "Mapping of a region within the N terminus of Jak1 involved in cytokine receptor interaction" . J. Biol. Chem . 276 (40): 37451– 8. doi :10.1074/jbc.M106135200 PMID 11468294 . ↑ Kim H, Baumann H (December 1997). "Transmembrane domain of gp130 contributes to intracellular signal transduction in hepatic cells" . J. Biol. Chem . 272 (49): 30741– 7. doi :10.1074/jbc.272.49.30741 PMID 9388212 . ↑ Haan C, Heinrich PC, Behrmann I (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 . 361 (Pt 1): 105– 11. doi :10.1042/0264-6021:3610105 . PMC 1222284 PMID 11742534 . ↑ Kim H, Lee YH, 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 . 286 (5): 886– 94. Bibcode :2001BBRC..286..886K . doi :10.1006/bbrc.2001.5496 . PMID 11527382 . ↑ Giorgetti-Peraldi S, Peyrade F, Baron V, Van Obberghen E (December 1995). "Involvement of Janus kinases in the insulin signaling pathway" . Eur. J. Biochem . 234 (2): 656– 60. doi :10.1111/j.1432-1033.1995.656_b.x PMID 8536716 . 1 2 Usacheva A, Kotenko S, Witte MM, Colamonici OR (August 2002). "Two distinct domains within the N-terminal region of Janus kinase 1 interact with cytokine receptors" . J. Immunol . 169 (3): 1302– 8. doi :10.4049/jimmunol.169.3.1302 PMID 12133952 . ↑ Miyazaki T, Kawahara A, Fujii H, Nakagawa Y, Minami Y, Liu ZJ, et al. (November 1994). "Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits". Science . 266 (5187): 1045– 7. Bibcode :1994Sci...266.1045M . doi :10.1126/science.7973659 . PMID 7973659 . ↑ Russell SM, Johnston JA, Noguchi M, Kawamura M, Bacon CM, Friedmann M, et al. (November 1994). "Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID" . Science . 266 (5187): 1042– 5. Bibcode :1994Sci...266.1042R . doi :10.1126/science.7973658 . PMID 7973658 . ↑ Zhu MH, Berry JA, Russell SM, Leonard WJ (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 . 273 (17): 10719– 25. doi :10.1074/jbc.273.17.10719 PMID 9553136 . ↑ Migone TS, Rodig S, Cacalano NA, Berg M, Schreiber RD, Leonard WJ (November 1998). "Functional cooperation of the interleukin-2 receptor beta chain and Jak1 in phosphatidylinositol 3-kinase recruitment and phosphorylation" . Mol. Cell. Biol . 18 (11): 6416– 22. doi :10.1128/mcb.18.11.6416 . PMC 109227 PMID 9774657 . ↑ 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 . 139 (3): 884– 93. doi :10.1210/endo.139.3.5829 PMID 9492017 . ↑ Johnston JA, Wang LM, Hanson EP, Sun XJ, White MF, Oakes SA, et al. (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 . 270 (48): 28527– 30. doi :10.1074/jbc.270.48.28527 PMID 7499365 . ↑ Usacheva A, Sandoval R, Domanski P, Kotenko SV, Nelms K, Goldsmith MA, et al. (December 2002). "Contribution of the Box 1 and Box 2 motifs of cytokine receptors to Jak1 association and activation" . J. Biol. Chem . 277 (50): 48220– 6. doi :10.1074/jbc.M205757200 PMID 12374810 . ↑ Yin T, Shen R, Feng GS, Yang YC (January 1997). "Molecular characterization of specific interactions between SHP-2 phosphatase and JAK tyrosine kinases" . J. Biol. Chem . 272 (2): 1032– 7. doi :10.1074/jbc.272.2.1032 PMID 8995399 . ↑ Lehmann U, Schmitz J, Weissenbach M, Sobota RM, Hortner M, Friederichs K, et al. (January 2003). "SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gp130" . J. Biol. Chem . 278 (1): 661– 71. doi :10.1074/jbc.M210552200 PMID 12403768 . ↑ Pandey A, Fernandez MM, Steen H, Blagoev B, Nielsen MM, Roche S, et al. (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 . 275 (49): 38633– 9. doi :10.1074/jbc.M007849200 PMID 10993906 . ↑ Endo K, Takeshita T, Kasai H, Sasaki Y, Tanaka N, Asao H, et al. (July 2000). "STAM2, a new member of the STAM family, binding to the Janus kinases" . FEBS Lett . 477 (1– 2): 55– 61. Bibcode :2000FEBSL.477...55E . doi :10.1016/s0014-5793(00)01760-9 PMID 10899310 . ↑ Ueda T, Bruchovsky N, Sadar MD (March 2002). "Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways" . J. Biol. Chem . 277 (9): 7076– 85. doi :10.1074/jbc.M108255200 PMID 11751884 . ↑ 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 . 67 (2): 63– 71. doi :10.1034/j.1600-0609.2001.t01-1-00385.x . PMID 11722592 . S2CID 38074766 . 1 2 Fujitani Y, Hibi M, Fukada T, Takahashi-Tezuka M, Yoshida H, Yamaguchi T, et al. (February 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 . ↑ Guo D, Dunbar JD, Yang CH, Pfeffer LM, Donner DB (March 1998). "Induction of Jak/STAT signaling by activation of the type 1 TNF receptor" . J. Immunol . 160 (6): 2742– 50. doi :10.4049/jimmunol.160.6.2742 PMID 9510175 . ↑ Miscia S, Marchisio M, Grilli A, Di Valerio V, Centurione L, Sabatino G, et al. (January 2002). "Tumor necrosis factor alpha (TNF-alpha) activates Jak1/Stat3-Stat5B signaling through TNFR-1 in human B cells". Cell Growth Differ . 13 (1): 13– 8. PMID 11801527 .
Further reading
Donnelly RP, Dickensheets H, Finbloom DS (1999). "The interleukin-10 signal transduction pathway and regulation of gene expression in mononuclear phagocytes" . J. Interferon Cytokine Res . 19 (6): 563– 73. doi :10.1089/107999099313695 . PMID 10433356 . Carter-Su C, Rui L, Stofega MR (2000). "SH2-B and SIRP: JAK2 binding proteins that modulate the actions of growth hormone". Recent Prog. Horm. Res . 55 : 293– 311. PMID 11036942 . Kostrodymova GM (1976). "[An experimental study of the possible sensitizing properties of triethanolamine contained in chemical compounds used at home]". Gigiena i Sanitariia (6): 10– 2. PMID 1213395 . Howard OM, Dean M, Young H, Ramsburg M, Turpin JA, Michiel DF, et al. (1992). "Characterization of a class 3 tyrosine kinase". Oncogene . 7 (5): 895– 900. PMID 1373877 . Pritchard MA, Baker E, Callen DF, Sutherland GR, Wilks AF (1992). "Two members of the JAK family of protein tyrosine kinases map to chromosomes 1p31.3 and 9p24". Mamm. Genome . 3 (1): 36– 8. doi :10.1007/BF00355839 . PMID 1581631 . S2CID 31384629 . Wilks AF, Harpur AG, Kurban RR, Ralph SJ, Zürcher G, Ziemiecki A (1991). "Two novel protein-tyrosine kinases, each with a second phosphotransferase-related catalytic domain, define a new class of protein kinase" . Mol. Cell. Biol . 11 (4): 2057– 65. doi :10.1128/MCB.11.4.2057 . PMC 359893 PMID 1848670 . Johnston JA, Wang LM, Hanson EP, Sun XJ, White MF, Oakes SA, 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 . Nicholson SE, Oates AC, Harpur AG, Ziemiecki A, Wilks AF, Layton JE (1994). "Tyrosine kinase JAK1 is associated with the granulocyte-colony-stimulating factor receptor and both become tyrosine-phosphorylated after receptor activation" . Proc. Natl. Acad. Sci. U.S.A . 91 (8): 2985– 8. Bibcode :1994PNAS...91.2985N . doi :10.1073/pnas.91.8.2985 PMC 43499 PMID 7512720 . Domanski P, Yan H, Witte MM, Krolewski J, Colamonici OR (1995). "Homodimerization and intermolecular tyrosine phosphorylation of the Tyk-2 tyrosine kinase" . FEBS Lett . 374 (3): 317– 22. Bibcode :1995FEBSL.374..317D . doi :10.1016/0014-5793(95)01094-U PMID 7589562 . Modi WS, Farrar WL, Howard OM (1995). "Confirmed assignment of a novel human tyrosine kinase gene (JAK1A) to 1p32.3→p31.3 by nonisotopic in situ hybridization" . Cytogenet. Cell Genet . 69 (3– 4): 232– 4. doi :10.1159/000133971 . PMID 7698020 . Miyazaki T, Kawahara A, Fujii H, Nakagawa Y, Minami Y, Liu Z, et al. (1994). "Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits". Science . 266 (5187): 1045– 7. Bibcode :1994Sci...266.1045M . doi :10.1126/science.7973659 . PMID 7973659 . Müller M, Briscoe J, Laxton C, Guschin D, Ziemiecki A, Silvennoinen O, et al. (1993). "The protein tyrosine kinase JAK1 complements defects in interferon-alpha/beta and -gamma signal transduction". Nature . 366 (6451): 129– 35. Bibcode :1993Natur.366..129M . doi :10.1038/366129a0 . PMID 8232552 . S2CID 27334189 . Lee ST, Strunk KM, Spritz RA (1993). "A survey of protein tyrosine kinase mRNAs expressed in normal human melanocytes". Oncogene . 8 (12): 3403– 10. PMID 8247543 . Lütticken C, Wegenka UM, Yuan J, Buschmann J, Schindler C, Ziemiecki A, et al. (1994). "Association of transcription factor APRF and protein kinase Jak1 with the interleukin-6 signal transducer gp130". Science . 263 (5143): 89– 92. Bibcode :1994Sci...263...89L . doi :10.1126/science.8272872 . PMID 8272872 . Giorgetti-Peraldi S, Peyrade F, Baron V, Van Obberghen E (1996). "Involvement of Janus kinases in the insulin signaling pathway" . Eur. J. Biochem . 234 (2): 656– 60. doi :10.1111/j.1432-1033.1995.656_b.x PMID 8536716 . Friedmann MC, Migone TS, Russell SM, Leonard WJ (1996). "Different interleukin 2 receptor beta-chain tyrosines couple to at least two signaling pathways and synergistically mediate interleukin 2-induced proliferation" . Proc. Natl. Acad. Sci. U.S.A . 93 (5): 2077– 82. Bibcode :1996PNAS...93.2077F . doi :10.1073/pnas.93.5.2077 PMC 39912 PMID 8700888 . Gauzzi MC, Velazquez L, McKendry R, Mogensen KE, Fellous M, Pellegrini S (1996). "Interferon-alpha-dependent activation of Tyk2 requires phosphorylation of positive regulatory tyrosines by another kinase" . J. Biol. Chem . 271 (34): 20494– 500. doi :10.1074/jbc.271.34.20494 PMID 8702790 . Demoulin JB, Uyttenhove C, Van Roost E, Delestré B, Donckers D, Van Snick J, et al. (1996). "A single tyrosine of the interleukin-9 (IL-9) receptor is required for STAT activation, antiapoptotic activity, and growth regulation by IL-9" . Mol. Cell. Biol . 16 (9): 4710– 6. doi :10.1128/MCB.16.9.4710 . PMC 231471 PMID 8756628 . Yin T, Shen R, Feng GS, Yang YC (1997). "Molecular characterization of specific interactions between SHP-2 phosphatase and JAK tyrosine kinases" . J. Biol. Chem . 272 (2): 1032– 7. doi :10.1074/jbc.272.2.1032 PMID 8995399 . Bluyssen HA, Levy DE (1997). "Stat2 is a transcriptional activator that requires sequence-specific contacts provided by stat1 and p48 for stable interaction with DNA" . J. Biol. Chem . 272 (7): 4600– 5. doi :10.1074/jbc.272.7.4600 PMID 9020188 .
External links
Activity Regulation Classification Kinetics Types
Chemokine CSF
Interferon
IFNAR (α/β, I)
Agonists: Albinterferon Interferon alpha (interferon alfa, IFN-α) Interferon alfa (IFNA1 , IFNA2 , IFNA4 , IFNA5 , IFNA6 , IFNA7 , IFNA8 , IFNA10 , IFNA13 , IFNA14 , IFNA16 , IFNA17 , IFNA21 )Interferon alfa 2a Interferon alfa 2b Interferon alfa n1 Interferon alfacon-1 Interferon alpha-n3 Interferon beta (IFN-β) (IFNB1 , IFNB3 )Interferon beta 1a Interferon beta 1b Interferon kappa (IFN-ε/κ/τ/ζ, IFNK) Interferon omega (IFN-ω, IFNW1) Peginterferon alfa-2a Peginterferon alfa-2b IFNGR (γ, II) IFNLR (λ, III)
See IL-28R (IFNLR) here instead.
Interleukin TGFβ TNF Others
