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] 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.[6] 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.[7]

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, JAK1A, JAK1B, JTK3, Janus kinase 1
External IDs	OMIM: 147795 MGI: 96628 HomoloGene: 1678 GeneCards: JAK1
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p31.3 Start 64,833,229 bp[1] End 65,067,754 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4 C6|4 46.19 cM Start 101,152,367 bp[2] End 101,265,282 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • transferase activity • nucleotide binding • protein kinase activity • CCR5 chemokine receptor binding • growth hormone receptor binding • metal ion binding • kinase activity • GO:0001948 protein binding • protein tyrosine kinase activity • protein phosphatase binding • receptor binding • ATP binding • ubiquitin protein ligase binding • non-membrane spanning protein tyrosine kinase activity • Ras guanyl-nucleotide exchange factor activity Cellular component • cytoplasm • cytosol • membrane • focal adhesion • extrinsic component of cytoplasmic side of plasma membrane • cytoskeleton • endomembrane system • cell nucleus • endosome Biological process • cell differentiation • GO:0007243 intracellular signal transduction • phosphorylation • transmembrane receptor protein tyrosine kinase signaling pathway • interferon-gamma-mediated signaling pathway • response to antibiotic • MAPK cascade • positive regulation of sprouting angiogenesis • protein phosphorylation • regulation of type I interferon-mediated signaling pathway • regulation of interferon-gamma-mediated signaling pathway • regulation of cell proliferation • type I interferon signaling pathway • interleukin-2-mediated signaling pathway • peptidyl-tyrosine autophosphorylation • autophosphorylation • cell migration • innate immune system • interleukin-12-mediated signaling pathway • interleukin-7-mediated signaling pathway • interleukin-15-mediated signaling pathway • interleukin-9-mediated signaling pathway • regulation of molecular function • peptidyl-tyrosine phosphorylation • cytokine-mediated signaling pathway • interleukin-21-mediated signaling pathway • interleukin-6-mediated signaling pathway • interleukin-27-mediated signaling pathway • interleukin-35-mediated signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	3716	16451
Ensembl	ENSG00000162434	ENSMUSG00000028530
UniProt	P23458	P52332
RefSeq (mRNA)	NM_002227 NM_001320923 NM_001321852 NM_001321853 NM_001321854 NM_001321855 NM_001321856 NM_001321857	NM_146145 NM_013567
RefSeq (protein)	NP_001307852 NP_001308781 NP_001308782 NP_001308783 NP_001308784 NP_001308785 NP_001308786 NP_002218	n/a
Location (UCSC)	Chr 1: 64.83 – 65.07 Mb	Chr 4: 101.15 – 101.27 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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] and
• TNFRSF1A.[30][31]

References

1. GRCh38: Ensembl release 89: ENSG00000162434 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000028530 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. 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.
7. Christian Nordqvist. "Protein JAK Makes Cancer Cells Contract, So They Can Squeeze Out Of A Tumor". Medical News Today.
8. 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. doi:10.1073/pnas.170192197. PMC 27739. PMID 10954736.
9. 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.
10. Haan C, Is'harc H, Hermanns HM, Schmitz-Van De Leur H, Kerr IM, Heinrich PC, Grötzinger J, Behrmann I (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.
11. 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.
12. 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.
13. 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. doi:10.1006/bbrc.2001.5496. PMID 11527382.
14. 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.
15. 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.
16. Miyazaki T, Kawahara A, Fujii H, Nakagawa Y, Minami Y, Liu ZJ, Oishi I, Silvennoinen O, Witthuhn BA, Ihle JN (November 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.
17. Russell SM, Johnston JA, Noguchi M, Kawamura M, Bacon CM, Friedmann M, Berg M, McVicar DW, Witthuhn BA, Silvennoinen O (November 1994). "Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID" (PDF). Science. 266 (5187): 1042–5. doi:10.1126/science.7973658. PMID 7973658.
18. 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.
19. 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.
20. 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.
21. Johnston JA, Wang LM, Hanson EP, Sun XJ, White MF, Oakes SA, Pierce JH, O'Shea JJ (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.
22. Usacheva A, Sandoval R, Domanski P, Kotenko SV, Nelms K, Goldsmith MA, Colamonici OR (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.
23. 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.
24. Lehmann U, Schmitz J, Weissenbach M, Sobota RM, Hortner M, Friederichs K, Behrmann I, Tsiaris W, Sasaki A, Schneider-Mergener J, Yoshimura A, Neel BG, Heinrich PC, Schaper F (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.
25. Pandey A, Fernandez MM, Steen H, Blagoev B, Nielsen MM, Roche S, Mann M, Lodish HF (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.
26. Endo K, Takeshita T, Kasai H, Sasaki Y, Tanaka N, Asao H, Kikuchi K, Yamada M, Chenb M, O'Shea JJ, Sugamura K (July 2000). "STAM2, a new member of the STAM family, binding to the Janus kinases". FEBS Lett. 477 (1–2): 55–61. doi:10.1016/s0014-5793(00)01760-9. PMID 10899310.
27. 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.
28. 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.
29. 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. 14 (7): 751–61. doi:10.1038/sj.onc.1200907. PMID 9047382.
30. 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. PMID 9510175.
31. Miscia S, Marchisio M, Grilli A, Di Valerio V, Centurione L, Sabatino G, Garaci F, Zauli G, Bonvini E, Di Baldassarre A (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, et al. (1992). "Characterization of a class 3 tyrosine kinase". Oncogene. 7 (5): 895–900. PMID 1373877.
• Pritchard MA, Baker E, Callen DF, et al. (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.
• Wilks AF, Harpur AG, Kurban RR, et al. (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, 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, et al. (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. doi:10.1073/pnas.91.8.2985. PMC 43499. PMID 7512720.
• Domanski P, Yan H, Witte MM, et al. (1995). "Homodimerization and intermolecular tyrosine phosphorylation of the Tyk-2 tyrosine kinase". FEBS Lett. 374 (3): 317–22. 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, 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.
• Müller M, Briscoe J, Laxton C, et al. (1993). "The protein tyrosine kinase JAK1 complements defects in interferon-alpha/beta and -gamma signal transduction". Nature. 366 (6451): 129–35. doi:10.1038/366129a0. PMID 8232552.
• 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, et al. (1994). "Association of transcription factor APRF and protein kinase Jak1 with the interleukin-6 signal transducer gp130". Science. 263 (5143): 89–92. 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. doi:10.1073/pnas.93.5.2077. PMC 39912. PMID 8700888.
• Gauzzi MC, Velazquez L, McKendry R, et al. (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, 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

• Janus+Kinase+1 at the US National Library of Medicine Medical Subject Headings (MeSH)