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Gene Review

Jak1  -  Janus kinase 1

Rattus norvegicus

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Disease relevance of Jak1


Psychiatry related information on Jak1

  • We have recently shown (Morales, O., Lindgren, U., and Haldosen, L. A. (2000) J. Bone Miner. Res. 15, 2284-2290) that UMR 106 cells express a GH-responsive JAK2/STAT5 signaling system [5].

High impact information on Jak1

  • Nitric oxide and thiol redox regulation of Janus kinase activity [6].
  • Ang II has been shown to activate the Janus kinase/signal transducer(s) and activator(s) of transcription (JAK/STAT) pathway, suggesting similarities to cytokine signaling [7].
  • Leptin is a 16-kd hormone that mediates a range of metabolic effects by using a transduction pathway from the long form of the leptin receptor, OB-R(L,) through Janus kinase-signal transducer and activator of transcription (Jak-Stat) signaling components [8].
  • Furthermore, the Janus kinase inhibitor, tyrphostin AG490, inhibited the constitutive activation of Stat3 and suppressed the growth of human prostate cancer cells [9].
  • There is an increase in immunoreactivity of Janus kinase (JAK2), a CNTF-regulated protein tyrosine kinase, in the VTA after chronic but not acute cocaine administration [10].

Chemical compound and disease context of Jak1


Biological context of Jak1


Anatomical context of Jak1


Associations of Jak1 with chemical compounds

  • Instead, in solid phase kinase assays using a glutathione S-transferase-c-Jun fusion protein (amino acids 1-79) as the substrate, a significant activation of the mitogen-activated protein Janus kinase (c-Jun N-terminal kinase; JNK) was observed [18].
  • However, BAPTA-AM prolonged the DNA binding activity of STAT5 without affecting STAT5 or JAK2 protein levels [19].
  • Activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) intracellular signaling pathway by Ang II mediates at least some of the mitogenic responses to this hormone [20].
  • The purpose of this study was to determine whether myocardial JAK or STAT is activated in ischemic heart, and to evaluate the angiotensin blockade on the pathway [2].
  • Anti-inflammatory roles of retinoic acid in rat brain astrocytes: Suppression of interferon-gamma-induced JAK/STAT phosphorylation [21].

Regulatory relationships of Jak1


Other interactions of Jak1

  • Inhibition of Src with PP2 {4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine} and a DN-Src (dominant-negative Src) construct prevented the activation of Akt, JAK (Janus kinase) and STAT3 [27].
  • In UMR 106 cells, GH induced the expression of the JAK/STAT negative regulatory proteins SOCS-3 and CIS [5].
  • It is suggested that the kinase activity of Jak1 mediates nuclear translocation of Stat3 in astrocytes, and that this signaling pathway is involved in the astroglial response to focal cerebral ischemia [1].
  • These results suggest that RA induces an anti-inflammatory effect by suppressing the activation of the JAK/STAT pathway in IFN-gamma-treated astrocytes [21].
  • In conclusion, Epo given after FCI in neonatal rats provides significant neuroprotection, mediated possibly by activation of the Janus kinase-signal transducer and activator of transcription-Bcl-xL signaling pathways [24].

Analytical, diagnostic and therapeutic context of Jak1


  1. Activation of the JAK/STAT pathway following transient focal cerebral ischemia: signaling through Jak1 and Stat3 in astrocytes. Justicia, C., Gabriel, C., Planas, A.M. Glia (2000) [Pubmed]
  2. Myocardial ischemia activates the JAK-STAT pathway through angiotensin II signaling in in vivo myocardium of rats. Omura, T., Yoshiyama, M., Ishikura, F., Kobayashi, H., Takeuchi, K., Beppu, S., Yoshikawa, J. J. Mol. Cell. Cardiol. (2001) [Pubmed]
  3. Angiotensin II blockade prevents hyperglycemia-induced activation of JAK and STAT proteins in diabetic rat kidney glomeruli. Banes, A.K., Shaw, S., Jenkins, J., Redd, H., Amiri, F., Pollock, D.M., Marrero, M.B. Am. J. Physiol. Renal Physiol. (2004) [Pubmed]
  4. Role of the Janus kinase (JAK)/signal transducters and activators of transcription (STAT) cascade in advanced glycation end-product-induced cellular mitogenesis in NRK-49F cells. Huang, J.S., Guh, J.Y., Hung, W.C., Yang, M.L., Lai, Y.H., Chen, H.C., Chuang, L.Y. Biochem. J. (1999) [Pubmed]
  5. 1Alpha,25-dihydroxyvitamin D3 inhibits GH-induced expression of SOCS-3 and CIS and prolongs growth hormone signaling via the Janus kinase (JAK2)/signal transducers and activators of transcription (STAT5) system in osteoblast-like cells. Morales, O., Faulds, M.H., Lindgren, U.J., Haldosén, L.A. J. Biol. Chem. (2002) [Pubmed]
  6. Nitric oxide and thiol redox regulation of Janus kinase activity. Duhé, R.J., Evans, G.A., Erwin, R.A., Kirken, R.A., Cox, G.W., Farrar, W.L. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  7. Angiotensin II stimulates p21-activated kinase in vascular smooth muscle cells: role in activation of JNK. Schmitz, U., Ishida, T., Ishida, M., Surapisitchat, J., Hasham, M.I., Pelech, S., Berk, B.C. Circ. Res. (1998) [Pubmed]
  8. Leptin in hepatic fibrosis: evidence for increased collagen production in stellate cells and lean littermates of ob/ob mice. Saxena, N.K., Ikeda, K., Rockey, D.C., Friedman, S.L., Anania, F.A. Hepatology (2002) [Pubmed]
  9. Inhibition of constitutively activated Stat3 signaling pathway suppresses growth of prostate cancer cells. Ni, Z., Lou, W., Leman, E.S., Gao, A.C. Cancer Res. (2000) [Pubmed]
  10. Influence of cocaine on the JAK-STAT pathway in the mesolimbic dopamine system. Berhow, M.T., Hiroi, N., Kobierski, L.A., Hyman, S.E., Nestler, E.J. J. Neurosci. (1996) [Pubmed]
  11. HIV glycoprotein 120 enhances intercellular adhesion molecule-1 gene expression in glial cells. Involvement of Janus kinase/signal transducer and activator of transcription and protein kinase C signaling pathways. Shrikant, P., Benos, D.J., Tang, L.P., Benveniste, E.N. J. Immunol. (1996) [Pubmed]
  12. Cytokine G-protein signaling crosstalk in cardiomyocytes: attenuation of Jak-STAT activation by endothelin-1. Booz, G.W., Day, J.N., Speth, R., Baker, K.M. Mol. Cell. Biochem. (2002) [Pubmed]
  13. The immunohistochemical localization of signal-transduction pathway components Jak1, Jak2, Jak3, Tyk2 and STAT-1 during early enamel and dentine formation in rat molars. Tanase, S., Bawden, J.W. Arch. Oral Biol. (1996) [Pubmed]
  14. Leptin Inhibits Apoptosis in Thymus through a Janus Kinase-2-Independent, Insulin Receptor Substrate-1/Phosphatidylinositol-3 Kinase-Dependent Pathway. Mansour, E., Pereira, F.G., Ara??jo, E.P., Amaral, M.E., Morari, J., Ferraroni, N.R., Ferreira, D.S., Lorand-Metze, I., Velloso, L.A. Endocrinology (2006) [Pubmed]
  15. Role of Janus kinase/signal transducer and activator of transcription and mitogen-activated protein kinase cascades in angiotensin II- and platelet-derived growth factor-induced vascular smooth muscle cell proliferation. Marrero, M.B., Schieffer, B., Li, B., Sun, J., Harp, J.B., Ling, B.N. J. Biol. Chem. (1997) [Pubmed]
  16. Thyrotropin modulates interferon-gamma-mediated intercellular adhesion molecule-1 gene expression by inhibiting Janus kinase-1 and signal transducer and activator of transcription-1 activation in thyroid cells. Chung, J., Park, E.S., Kim, D., Suh, J.M., Chung, H.K., Kim, J., Kim, H., Park, S.J., Kwon, O.Y., Ro, H.K., Shong, M. Endocrinology (2000) [Pubmed]
  17. 15d-PGJ2 and rosiglitazone suppress Janus kinase-STAT inflammatory signaling through induction of suppressor of cytokine signaling 1 (SOCS1) and SOCS3 in glia. Park, E.J., Park, S.Y., Joe, E.H., Jou, I. J. Biol. Chem. (2003) [Pubmed]
  18. Prolactin-induced cell proliferation in PC12 cells depends on JNK but not ERK activation. Cheng, Y., Zhizhin, I., Perlman, R.L., Mangoura, D. J. Biol. Chem. (2000) [Pubmed]
  19. Endoplasmic reticulum stress prolongs GH-induced Janus kinase (JAK2)/signal transducer and activator of transcription (STAT5) signaling pathway. Flores-Morales, A., Fernández, L., Rico-Bautista, E., Umana, A., Negrín, C., Zhang, J.G., Norstedt, G. Mol. Endocrinol. (2001) [Pubmed]
  20. Suppressor of cytokine signaling 3 is induced by angiotensin II in heart and isolated cardiomyocytes, and participates in desensitization. Calegari, V.C., Bezerra, R.M., Torsoni, M.A., Torsoni, A.S., Franchini, K.G., Saad, M.J., Velloso, L.A. Endocrinology (2003) [Pubmed]
  21. Anti-inflammatory roles of retinoic acid in rat brain astrocytes: Suppression of interferon-gamma-induced JAK/STAT phosphorylation. Choi, W.H., Ji, K.A., Jeon, S.B., Yang, M.S., Kim, H., Min, K.J., Shong, M., Jou, I., Joe, E.H. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  22. Members of the JAK/STAT proteins are expressed and regulated during development in the mammalian forebrain. De-Fraja, C., Conti, L., Magrassi, L., Govoni, S., Cattaneo, E. J. Neurosci. Res. (1998) [Pubmed]
  23. Interleukin-6 and ciliary neurotrophic factor trigger janus kinase activation and early gene response in rat hepatocytes. Wang, Y., Fuller, G.M. Gene (1995) [Pubmed]
  24. Erythropoietin after focal cerebral ischemia activates the Janus kinase-signal transducer and activator of transcription signaling pathway and improves brain injury in postnatal day 7 rats. Sola, A., Rogido, M., Lee, B.H., Genetta, T., Wen, T.C. Pediatr. Res. (2005) [Pubmed]
  25. Constitutive activation of STAT-3 and downregulation of SOCS-3 expression induced by adrenalectomy. Madiehe, A.M., Lin, L., White, C., Braymer, H.D., Bray, G.A., York, D.A. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2001) [Pubmed]
  26. Characterization of insulin-like growth factor-1-induced activation of the JAK/STAT pathway in rat cardiomyocytes. Takahashi, T., Fukuda, K., Pan, J., Kodama, H., Sano, M., Makino, S., Kato, T., Manabe, T., Ogawa, S. Circ. Res. (1999) [Pubmed]
  27. Integrin beta3-mediated Src activation regulates apoptosis in IEC-6 cells via Akt and STAT3. Bhattacharya, S., Ray, R.M., Johnson, L.R. Biochem. J. (2006) [Pubmed]
  28. Inhibition of preproinsulin gene expression by leptin induction of suppressor of cytokine signaling 3 in pancreatic beta-cells. Laubner, K., Kieffer, T.J., Lam, N.T., Niu, X., Jakob, F., Seufert, J. Diabetes (2005) [Pubmed]
  29. Insulin signalling in heart involves insulin receptor substrates-1 and -2, activation of phosphatidylinositol 3-kinase and the JAK 2-growth related pathway. Velloso, L.A., Carvalho, C.R., Rojas, F.A., Folli, F., Saad, M.J. Cardiovasc. Res. (1998) [Pubmed]
  30. Role of STAT3 in ischemic preconditioning. Hattori, R., Maulik, N., Otani, H., Zhu, L., Cordis, G., Engelman, R.M., Siddiqui, M.A., Das, D.K. J. Mol. Cell. Cardiol. (2001) [Pubmed]
  31. STAT signaling in ischemic heart: a role of STAT5A in ischemic preconditioning. Yamaura, G., Turoczi, T., Yamamoto, F., Siddqui, M.A., Maulik, N., Das, D.K. Am. J. Physiol. Heart Circ. Physiol. (2003) [Pubmed]
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