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Gene Review

Jak1  -  Janus kinase 1

Mus musculus

Synonyms: AA960307, BAP004, C130039L05Rik, JAK-1, Tyrosine-protein kinase JAK1
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Disease relevance of Jak1

  • However, Jak1-deficient, v-abl-transformed cell lines were more tumorgenic than wild-type cells when transplanted subcutaneously into severe combined immunodeficient (SCID) mice or injected intravenously into nude mice [1].
  • STAT3 activation was inhibited by either pharmacologically (AG490) through its upstream janus kinase (JAK2) or by a dominant-negative STAT3 adenovirus [2].
  • At the other end of the spectrum, JAK fusion proteins have been shown to play a role in leukemias [3].
  • The nonreceptor tyrosine kinases Jak1 and Jak3, which bind to the v-Abl oncoprotein, are constitutively activated in cells transformed with the Abelson murine leukemia virus [4].
  • We studied macrophage deactivation by examining the expression of a panel of IFN-gamma-inducible genes and activation of Janus Kinase (JAK)-STAT pathway in Mycobacterium avium-infected macrophages [5].

High impact information on Jak1

  • Suppressor of cytokine signalling-2 (SOCS-2) is a member of the suppressor of cytokine signalling family, a group of related proteins implicated in the negative regulation of cytokine action through inhibition of the Janus kinase (JAK) signal transducers and activators of transcription (STAT) signal-transduction pathway [6].
  • Cytokines exert their biological effect through binding to cell-surface receptors that are associated with one or more members of the JAK family of cytoplasmic tyrosine kinases [7].
  • Overexpression of either Jak1 or Jak2 stimulated p91 DNA-binding activity and p91-dependent transcription [8].
  • Dimerization of the receptor induces tyrosine phosphorylation and activation of the JAK kinase followed by phosphorylation of the receptor [9].
  • Coimmunoprecipitation experiments revealed that in these cells v-Abl was physically associated with Jak1 and Jak3 [10].

Chemical compound and disease context of Jak1


Biological context of Jak1


Anatomical context of Jak1

  • Jak1 deficiency leads to enhanced Abelson-induced B-cell tumor formation [1].
  • In the present studies, we have identified a series of end stage B cell (plasma cell) lines that fail to express Jak1, but phosphorylate STAT3 in response to IL-6 [20].
  • The overlapping and distinct protein tyrosine phosphorylation and activation of the same JAK1 kinase in T lymphocytes strongly suggests that IL-4 and IL-9 share the common signal transduction pathways and that the specificity for each cytokine could be achieved through the unique tyrosine-phosphorylated proteins triggered by individual cytokines [21].
  • Mouse brain microglia express interleukin-15 and its multimeric receptor complex functionally coupled to Janus kinase activity [22].
  • Possible involvement of Janus kinase Jak2 in interferon-gamma induction of nitric oxide synthase in rat glial cells [23].

Associations of Jak1 with chemical compounds

  • Both cytokines induced activation of Stat5, but only IL-7 induced activation of the Janus family kinases Jak1 and Jak3 [24].
  • However, using glutathione S-transferase fusion proteins containing amino- and carboxyl-terminal deletions of the betaL cytoplasmic domain, we demonstrate that the main Jak1-binding region (corresponding to AAs 300-346 on the beta subunit) is distinct from the Box 1 domain (AAs 287-295) [25].
  • In contrast, JAK-1 was not coprecipitated when coexpressed with a receptor alpha chain mutant containing alanine substitutions for the functionally critical residues 266-269 (LPKS) [26].
  • Janus kinase-signal transducer and activator of transcription mediates phosphatidic acid-induced interleukin (IL)-1beta and IL-6 production [27].
  • Activation of the JAK/STAT pathway, which is involved in cytokine signaling, was investigated in the gp55 signaling mediated by the erythropoietin receptor [28].

Physical interactions of Jak1


Regulatory relationships of Jak1


Other interactions of Jak1


Analytical, diagnostic and therapeutic context of Jak1


  1. Jak1 deficiency leads to enhanced Abelson-induced B-cell tumor formation. Sexl, V., Kovacic, B., Piekorz, R., Moriggl, R., Stoiber, D., Hoffmeyer, A., Liebminger, R., Kudlacek, O., Weisz, E., Rothammer, K., Ihle, J.N. Blood (2003) [Pubmed]
  2. STAT3 attenuates EGFR-mediated ERK activation and cell survival during oxidant stress in mouse proximal tubular cells. Arany, I., Megyesi, J.K., Nelkin, B.D., Safirstein, R.L. Kidney Int. (2006) [Pubmed]
  3. Janus kinases and their role in growth and disease. Aringer, M., Cheng, A., Nelson, J.W., Chen, M., Sudarshan, C., Zhou, Y.J., O'Shea, J.J. Life Sci. (1999) [Pubmed]
  4. Functional involvement of Akt signaling downstream of Jak1 in v-Abl-induced activation of hematopoietic cells. Oki, S., Limnander, A., Danial, N.N., Rothman, P.B. Blood (2002) [Pubmed]
  5. Mycobacterium avium infection of mouse macrophages inhibits IFN-gamma Janus kinase-STAT signaling and gene induction by down-regulation of the IFN-gamma receptor. Hussain, S., Zwilling, B.S., Lafuse, W.P. J. Immunol. (1999) [Pubmed]
  6. Gigantism in mice lacking suppressor of cytokine signalling-2. Metcalf, D., Greenhalgh, C.J., Viney, E., Willson, T.A., Starr, R., Nicola, N.A., Hilton, D.J., Alexander, W.S. Nature (2000) [Pubmed]
  7. A new protein containing an SH2 domain that inhibits JAK kinases. Endo, T.A., Masuhara, M., Yokouchi, M., Suzuki, R., Sakamoto, H., Mitsui, K., Matsumoto, A., Tanimura, S., Ohtsubo, M., Misawa, H., Miyazaki, T., Leonor, N., Taniguchi, T., Fujita, T., Kanakura, Y., Komiya, S., Yoshimura, A. Nature (1997) [Pubmed]
  8. Interferon-induced nuclear signalling by Jak protein tyrosine kinases. Silvennoinen, O., Ihle, J.N., Schlessinger, J., Levy, D.E. Nature (1993) [Pubmed]
  9. Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Bole-Feysot, C., Goffin, V., Edery, M., Binart, N., Kelly, P.A. Endocr. Rev. (1998) [Pubmed]
  10. Jak-STAT signaling induced by the v-abl oncogene. Danial, N.N., Pernis, A., Rothman, P.B. Science (1995) [Pubmed]
  11. Activation of the JAK1-STAT5 pathway by binding of the Friend virus gp55 glycoprotein to the erythropoietin receptor. Yamamura, Y., Senda, H., Noda, M., Ikawa, Y. Leukemia (1997) [Pubmed]
  12. A transient dephosphorylation of JAK1 and JAK2 characterises the early-phase response of murine erythroleukemia cells to the differentiation inducer hexamethylenebisacetamide. Arcangeli, A., Fontana, L., Crociani, O., Cherubini, A., Hofmann, G., Piccini, E., Polvani, S., D'Amico, M., Carlà, M., Olivotto, M. Leukemia (2000) [Pubmed]
  13. The Jak1 SH2 domain does not fulfill a classical SH2 function in Jak/STAT signaling but plays a structural role for receptor interaction and up-regulation of receptor surface expression. Radtke, S., Haan, S., Jörissen, A., Hermanns, H.M., Diefenbach, S., Smyczek, T., Schmitz-Vandeleur, H., Heinrich, P.C., Behrmann, I., Haan, C. J. Biol. Chem. (2005) [Pubmed]
  14. 1,25 dihydroxyvitamin-D3 modulates JAK-STAT pathway in IL-12/IFNgamma axis leading to Th1 response in experimental allergic encephalomyelitis. Muthian, G., Raikwar, H.P., Rajasingh, J., Bright, J.J. J. Neurosci. Res. (2006) [Pubmed]
  15. Arf gene loss enhances oncogenicity and limits imatinib response in mouse models of Bcr-Abl-induced acute lymphoblastic leukemia. Williams, R.T., Roussel, M.F., Sherr, C.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  16. Crosstalk between PKCzeta and the IL4/Stat6 pathway during T-cell-mediated hepatitis. Durán, A., Rodriguez, A., Martin, P., Serrano, M., Flores, J.M., Leitges, M., Diaz-Meco, M.T., Moscat, J. EMBO J. (2004) [Pubmed]
  17. Homodimerization of interleukin-4 receptor alpha chain can induce intracellular signaling. Kammer, W., Lischke, A., Moriggl, R., Groner, B., Ziemiecki, A., Gurniak, C.B., Berg, L.J., Friedrich, K. J. Biol. Chem. (1996) [Pubmed]
  18. Activation of Stat3 by v-Src is through a Ras-independent pathway. Liu, J.J., Nakajima, K., Hirano, T., Yang-Yen, H.F. J. Biomed. Sci. (1998) [Pubmed]
  19. The Role of Interleukin-11 in Pregnancy Involves Up-Regulation of {alpha}2-Macroglobulin Gene through Janus Kinase 2-Signal Transducer and Activator of Transcription 3 Pathway in the Decidua. Bao, L., Devi, S., Bowen-Shauver, J., Ferguson-Gottschall, S., Robb, L., Gibori, G. Mol. Endocrinol. (2006) [Pubmed]
  20. IL-6 mediated activation of STAT3 bypasses Janus kinases in terminally differentiated B lineage cells. Kopantzev, Y., Heller, M., Swaminathan, N., Rudikoff, S. Oncogene (2002) [Pubmed]
  21. JAK1 kinase forms complexes with interleukin-4 receptor and 4PS/insulin receptor substrate-1-like protein and is activated by interleukin-4 and interleukin-9 in T lymphocytes. Yin, T., Tsang, M.L., Yang, Y.C. J. Biol. Chem. (1994) [Pubmed]
  22. Mouse brain microglia express interleukin-15 and its multimeric receptor complex functionally coupled to Janus kinase activity. Hanisch, U.K., Lyons, S.A., Prinz, M., Nolte, C., Weber, J.R., Kettenmann, H., Kirchhoff, F. J. Biol. Chem. (1997) [Pubmed]
  23. Possible involvement of Janus kinase Jak2 in interferon-gamma induction of nitric oxide synthase in rat glial cells. Kitamura, Y., Takahashi, H., Nomura, Y., Taniguchi, T. Eur. J. Pharmacol. (1996) [Pubmed]
  24. Thymic stromal lymphopoietin: a cytokine that promotes the development of IgM+ B cells in vitro and signals via a novel mechanism. Levin, S.D., Koelling, R.M., Friend, S.L., Isaksen, D.E., Ziegler, S.F., Perlmutter, R.M., Farr, A.G. J. Immunol. (1999) [Pubmed]
  25. A region of the beta subunit of the interferon alpha receptor different from box 1 interacts with Jak1 and is sufficient to activate the Jak-Stat pathway and induce an antiviral state. Domanski, P., Fish, E., Nadeau, O.W., Witte, M., Platanias, L.C., Yan, H., Krolewski, J., Pitha, P., Colamonici, O.R. J. Biol. Chem. (1997) [Pubmed]
  26. Identification of an interferon-gamma receptor alpha chain sequence required for JAK-1 binding. Kaplan, D.H., Greenlund, A.C., Tanner, J.W., Shaw, A.S., Schreiber, R.D. J. Biol. Chem. (1996) [Pubmed]
  27. Janus kinase-signal transducer and activator of transcription mediates phosphatidic acid-induced interleukin (IL)-1beta and IL-6 production. Lee, C., Lim, H.K., Sakong, J., Lee, Y.S., Kim, J.R., Baek, S.H. Mol. Pharmacol. (2006) [Pubmed]
  28. Pathogenesis of Friend leukemia virus. Ikawa, Y. Leukemia (1997) [Pubmed]
  29. Identification of JAK protein tyrosine kinases as signaling molecules for prolactin. Functional analysis of prolactin receptor and prolactin-erythropoietin receptor chimera expressed in lymphoid cells. Dusanter-Fourt, I., Muller, O., Ziemiecki, A., Mayeux, P., Drucker, B., Djiane, J., Wilks, A., Harpur, A.G., Fischer, S., Gisselbrecht, S. EMBO J. (1994) [Pubmed]
  30. The conserved box 1 motif of cytokine receptors is required for association with JAK kinases. Tanner, J.W., Chen, W., Young, R.L., Longmore, G.D., Shaw, A.S. J. Biol. Chem. (1995) [Pubmed]
  31. In vitro activation of Stat3 by epidermal growth factor receptor kinase. Park, O.K., Schaefer, T.S., Nathans, D. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  32. Jak2 and Tyk2 are necessary for lineage-specific differentiation, but not for the maintenance of self-renewal of mouse embryonic stem cells. Chung, B.M., Kang, H.C., Han, S.Y., Heo, H.S., Lee, J.J., Jeon, J., Lim, J.Y., Shin, I., Hong, S.H., Cho, Y.S., Kim, C.G. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  33. Megakaryocyte growth and development factor and interleukin-3 induce patterns of protein-tyrosine phosphorylation that correlate with dominant differentiation over proliferation of mpl-transfected 32D cells. Mu, S.X., Xia, M., Elliott, G., Bogenberger, J., Swift, S., Bennett, L., Lappinga, D.L., Hecht, R., Lee, R., Saris, C.J. Blood (1995) [Pubmed]
  34. Erythropoietin and interleukin-2 activate distinct JAK kinase family members. Barber, D.L., D'Andrea, A.D. Mol. Cell. Biol. (1994) [Pubmed]
  35. Identification of critical residues required for suppressor of cytokine signaling-specific regulation of interleukin-4 signaling. Haque, S.J., Harbor, P.C., Williams, B.R. J. Biol. Chem. (2000) [Pubmed]
  36. Constitutive activation of JAK1 in Src-transformed cells. Campbell, G.S., Yu, C.L., Jove, R., Carter-Su, C. J. Biol. Chem. (1997) [Pubmed]
  37. Interleukin-9 induces tyrosine phosphorylation of insulin receptor substrate-1 via JAK tyrosine kinases. Yin, T., Keller, S.R., Quelle, F.W., Witthuhn, B.A., Tsang, M.L., Lienhard, G.E., Ihle, J.N., Yang, Y.C. J. Biol. Chem. (1995) [Pubmed]
  38. Erythropoietin induces sustained phosphorylation of STAT5 in primitive but not definitive erythrocytes generated from mouse embryonic stem cells. Tsuji-Takayama, K., Otani, T., Inoue, T., Nakamura, S., Motoda, R., Kibata, M., Orita, K. Exp. Hematol. (2006) [Pubmed]
  39. Insulin resistance-inducing cytokines differentially regulate SOCS mRNA expression via growth factor- and Jak/Stat-signaling pathways in 3T3-L1 adipocytes. Fasshauer, M., Kralisch, S., Klier, M., Lossner, U., Bluher, M., Klein, J., Paschke, R. J. Endocrinol. (2004) [Pubmed]
  40. Mechanical stretch activates the JAK/STAT pathway in rat cardiomyocytes. Pan, J., Fukuda, K., Saito, M., Matsuzaki, J., Kodama, H., Sano, M., Takahashi, T., Kato, T., Ogawa, S. Circ. Res. (1999) [Pubmed]
  41. JAK3: a novel JAK kinase associated with terminal differentiation of hematopoietic cells. Rane, S.G., Reddy, E.P. Oncogene (1994) [Pubmed]
  42. Prevention of islet allograft rejection in diabetic mice by targeting Janus Kinase 3 with 4-(4'-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline (JANEX-1). Cetkovic-Cvrlje, M., Dragt, A.L., Uckun, F.M. Arzneimittel-Forschung. (2003) [Pubmed]
  43. An essential role of the JAK-STAT pathway in ischemic preconditioning. Xuan, Y.T., Guo, Y., Han, H., Zhu, Y., Bolli, R. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  44. Molecular cloning of the murine JAK1 protein tyrosine kinase and its expression in the mouse central nervous system. Yang, X., Chung, D., Cepko, C.L. J. Neurosci. (1993) [Pubmed]
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