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Gene Review

Jak2  -  Janus kinase 2

Rattus norvegicus

Synonyms: JAK-2, Tyrosine-protein kinase JAK2
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Disease relevance of Jak2

  • Furthermore, this report identifies Jak2 as a potential therapeutic target in vascular diseases in which vascular smooth muscle cell apoptosis contributes to pathological progression [1].
  • Likewise, the oxidative stress, via the hypoxia/reoxygenation treatment of rat adult cardiomyocytes, produced apoptosis that was dependent upon activation of Jak2 [2].
  • In conclusion, our studies demonstrate that hyperglycemia induces activation of JAK2 and the STATs in vivo via an ANG II-dependent mechanism and that these proteins may be involved in the early kidney damage associated with diabetes [3].
  • Recombinant PL-Iv was shown to bind to ovarian and liver PRL receptors, stimulate the proliferation of Nb2 lymphoma cells, and activate Jak2 [4].
  • After myocardial ischemia, we analysed both activated levels and total amounts of JAK1, JAK2, STAT1 and STAT3 by Western blot analyses at 0, 5, 15, 30, 60, 120 and 240 min [5].

High impact information on Jak2

  • We show that EPOR-mediated activation of Jak2 leads to phosphorylation of the inhibitor of NF-kappaB (IkappaB), subsequent nuclear translocation of the transcription factor NF-kappaB, and NF-kappaB-dependent transcription of neuroprotective genes [6].
  • Activation of neuronal EPO receptors (EPORs) prevents apoptosis induced by NMDA (N-methyl-d-aspartate) or NO by triggering cross-talk between the signalling pathways of Janus kinase-2 (Jak2) and nuclear factor-kappaB (NF-kappaB) [6].
  • These results indicate that a PI3K-PDE3B-cAMP pathway interacting with the Janus kinase 2 (Jak2)-Stat3 pathway constitutes a critical component of leptin signaling in the hypothalamus [7].
  • However, GH-induced tyrosine phosphorylation of JAK2, STAT5, and STAT3 was 75% lower in the CRF animals [8].
  • SIRPalpha-induced NO production was prevented by inhibition of the tyrosine kinase JAK2 [9].

Chemical compound and disease context of Jak2


Biological context of Jak2


Anatomical context of Jak2

  • In contrast, in cells expressing a Jak2 dominant negative we observed that mitochondrial membrane integrity was preserved, and no caspase-9 activation occurred [1].
  • Angiotensin II activates Stat5 through Jak2 kinase in cardiac myocytes [15].
  • In this study, we provide evidence that the G-protein-coupled, Ang II type I (AT1) receptor couples to activation of Stat5 through Jak2 kinase in neonatal rat ventricular myocytes [15].
  • Translation of the rat Jak2 mRNA in rabbit reticulocytes results in a protein which is specifically immunoprecipitated by antibodies (Ab) recognizing JAK2, but not by Ab recognizing JAK1 [10].
  • Jak2 and STAT-1 colocalized in the proximal ends of presecretory and secretory-stage ameloblasts, supporting work by others that growth hormone receptor is located at that site [16].

Associations of Jak2 with chemical compounds


Physical interactions of Jak2

  • Competition experiments with synthetic peptides suggest that each of the YIPP amino acids, including tyrosine 319, is important in Jak2 binding to the AT1A receptor [20].
  • Co-immunoprecipitation with anti-insulin receptor antibody, anti-JAK2 antibody, and anti-IRS-1 antibody showed that JAK2 interacts with the insulin receptor and IRS-1 to form stable complexes following stimulation by insulin [21].

Enzymatic interactions of Jak2

  • Immunoanalyses showed that Epo induced a significant increase in phosphorylated Janus kinase 2 and signal transducer and activator of transcription-5 expressions at 1 and 3 d and up-regulated Bcl-xL expression by 24 h after FCI but did not affect Epo receptor or NF-kappaB expression [22].

Regulatory relationships of Jak2

  • Conversely, Jak1 was found expressed at a lower level compared to Jak2 and not modulated during brain maturation [23].
  • Furthermore, we have shown for the first time that decidual PRL may act locally to activate the Jak2/Stat5 pathway and up-regulate important genes involved in decidual growth and placentation [24].
  • These results support the main hypothesis that states that JAK2 plays a central role in the nicotinic alpha7 receptor-induced activation of the JAK2-PI-3K cascade in PC12 cells, which ultimately contribute to nAChR-mediated neuroprotection [25].
  • Either the JAK2 inhibitor AG-490 or the mitogen-activated protein (MAP) kinase inhibitor SB203580 abrogated the leptin-induced response in the WKY myocytes, whereas AG-490 unmasked a negative response in PS in the SHR myocytes [26].
  • Leptin is a JAK2-activating cytokine via the long form leptin receptor (Ob-Rb) [27].

Other interactions of Jak2

  • We found no significant differences in the relative expression of either Jak2, Stat5 (a and b), or SHP-2 in the two cell populations [28].
  • These results suggest that Jak2/Stat1 activation mediates cell death induced by proinflammatory cytokines and peroxides [14].
  • The colocalization of Jak1, Jak2 and STAT-1 along the proximal ends of presecretory and secretory ameloblasts suggests that the interferon receptor is up-regulated in these cells as well [16].
  • Furthermore, kinase-negative-Jak2, but not AG490, could inhibit Stat5b nuclear translocation and DNA binding [13].
  • Jak1, Tyk2 and STAT-1, but not Jak2 or Jak3, stain was seen in the odontoblasts [16].

Analytical, diagnostic and therapeutic context of Jak2


  1. Jak2 tyrosine kinase mediates oxidative stress-induced apoptosis in vascular smooth muscle cells. Sandberg, E.M., Sayeski, P.P. J. Biol. Chem. (2004) [Pubmed]
  2. Janus kinase-2 signaling mediates apoptosis in rat cardiomyocytes. Mascareno, E., Beckles, D.L., Siddiqui, M.A. Vascul. Pharmacol. (2005) [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. Placental lactogen-I variant utilizes the prolactin receptor signaling pathway. Cohick, C.B., Dai, G., Xu, L., Deb, S., Kamei, T., Levan, G., Szpirer, C., Szpirer, J., Kwok, S.C., Soares, M.J. Mol. Cell. Endocrinol. (1996) [Pubmed]
  5. 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]
  6. Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-kappaB signalling cascades. Digicaylioglu, M., Lipton, S.A. Nature (2001) [Pubmed]
  7. A phosphatidylinositol 3-kinase phosphodiesterase 3B-cyclic AMP pathway in hypothalamic action of leptin on feeding. Zhao, A.Z., Huan, J.N., Gupta, S., Pal, R., Sahu, A. Nat. Neurosci. (2002) [Pubmed]
  8. Impaired JAK-STAT signal transduction contributes to growth hormone resistance in chronic uremia. Schaefer, F., Chen, Y., Tsao, T., Nouri, P., Rabkin, R. J. Clin. Invest. (2001) [Pubmed]
  9. Signal regulatory protein alpha ligation induces macrophage nitric oxide production through JAK/STAT- and phosphatidylinositol 3-kinase/Rac1/NAPDH oxidase/H2O2-dependent pathways. Alblas, J., Honing, H., de Lavalette, C.R., Brown, M.H., Dijkstra, C.D., van den Berg, T.K. Mol. Cell. Biol. (2005) [Pubmed]
  10. Cloning of the gene encoding rat JAK2, a protein tyrosine kinase. Duhé, R.J., Rui, H., Greenwood, J.D., Garvey, K., Farrar, W.L. Gene (1995) [Pubmed]
  11. Inhibitory role of the somatostatin receptor SST2 on the intracrine-regulated cell proliferation induced by the 210-amino acid fibroblast growth factor-2 isoform: implication of JAK2. Hortala, M., Ferjoux, G., Estival, A., Bertrand, C., Schulz, S., Pradayrol, L., Susini, C., Clemente, F. J. Biol. Chem. (2003) [Pubmed]
  12. Herbimycin A suppresses NF-kappa B activation and tyrosine phosphorylation of JAK2 and the subsequent induction of nitric oxide synthase in C6 glioma cells. Nishiya, T., Uehara, T., Nomura, Y. FEBS Lett. (1995) [Pubmed]
  13. PRL-induced ERalpha gene expression is mediated by Janus kinase 2 (Jak2) while signal transducer and activator of transcription 5b (Stat5b) phosphorylation involves Jak2 and a second tyrosine kinase. Frasor, J., Barkai, U., Zhong, L., Fazleabas, A.T., Gibori, G. Mol. Endocrinol. (2001) [Pubmed]
  14. AG490 prevents cell death after exposure of rat astrocytes to hydrogen peroxide or proinflammatory cytokines: involvement of the Jak2/STAT pathway. Gorina, R., Petegnief, V., Chamorro, A., Planas, A.M. J. Neurochem. (2005) [Pubmed]
  15. Angiotensin II activates Stat5 through Jak2 kinase in cardiac myocytes. McWhinney, C.D., Dostal, D., Baker, K. J. Mol. Cell. Cardiol. (1998) [Pubmed]
  16. 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]
  17. S100B-RAGE-mediated augmentation of angiotensin II-induced activation of JAK2 in vascular smooth muscle cells is dependent on PLD2. Shaw, S.S., Schmidt, A.M., Banes, A.K., Wang, X., Stern, D.M., Marrero, M.B. Diabetes (2003) [Pubmed]
  18. JAK2/STAT3, not ERK1/2, mediates interleukin-6-induced activation of inducible nitric-oxide synthase and decrease in contractility of adult ventricular myocytes. Yu, X., Kennedy, R.H., Liu, S.J. J. Biol. Chem. (2003) [Pubmed]
  19. Exposure of glia to pro-oxidant agents revealed selective Stat1 activation by H2O2 and Jak2-independent antioxidant features of the Jak2 inhibitor AG490. Gorina, R., Sanfeliu, C., Galitó, A., Messeguer, A., Planas, A.M. Glia (2007) [Pubmed]
  20. Dependence on the motif YIPP for the physical association of Jak2 kinase with the intracellular carboxyl tail of the angiotensin II AT1 receptor. Ali, M.S., Sayeski, P.P., Dirksen, L.B., Hayzer, D.J., Marrero, M.B., Bernstein, K.E. J. Biol. Chem. (1997) [Pubmed]
  21. Insulin induces tyrosine phosphorylation of JAK2 in insulin-sensitive tissues of the intact rat. Saad, M.J., Carvalho, C.R., Thirone, A.C., Velloso, L.A. J. Biol. Chem. (1996) [Pubmed]
  22. 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]
  23. 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]
  24. Characterization of a rat uterine cell line, U(III) cells: prolactin (PRL) expression and endogenous regulation of PRL-dependent genes; estrogen receptor beta, alpha(2)-macroglobulin, and decidual PRL involving the Jak2 and Stat5 pathway. Prigent-Tessier, A., Barkai, U., Tessier, C., Cohen, H., Gibori, G. Endocrinology (2001) [Pubmed]
  25. The neuroprotective effect of 2-(3-pyridyl)-1-azabicyclo[3.2.2]nonane (TC-1698), a novel alpha7 ligand, is prevented through angiotensin II activation of a tyrosine phosphatase. Marrero, M.B., Papke, R.L., Bhatti, B.S., Shaw, S., Bencherif, M. J. Pharmacol. Exp. Ther. (2004) [Pubmed]
  26. Abrogated leptin-induced cardiac contractile response in ventricular myocytes under spontaneous hypertension: role of Jak/STAT pathway. Wold, L.E., Relling, D.P., Duan, J., Norby, F.L., Ren, J. Hypertension (2002) [Pubmed]
  27. Leptin and connective tissue growth factor in advanced glycation end-product-induced effects in NRK-49F cells. Lee, C.I., Guh, J.Y., Chen, H.C., Lin, K.H., Yang, Y.L., Hung, W.C., Lai, Y.H., Chuang, L.Y. J. Cell. Biochem. (2004) [Pubmed]
  28. Involvement of SOCS-1, the suppressor of cytokine signaling, in the prevention of prolactin-responsive gene expression in decidual cells. Barkai, U., Prigent-Tessier, A., Tessier, C., Gibori, G.B., Gibori, G. Mol. Endocrinol. (2000) [Pubmed]
  29. 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]
  30. Role of janus kinase-2 in insulin-mediated phosphorylation and inactivation of protein phosphatase-2A and its impact on upstream insulin signalling components. Begum, N., Ragolia, L. Biochem. J. (1999) [Pubmed]
  31. Role of oxidative stress in the increased activation of signal transducers and activators of transcription-3 in the fatty livers of obese Zucker rats. Dikdan, G.S., Saba, S.C., Dela Torre, A.N., Roth, J., Wang, S., Koneru, B. Surgery (2004) [Pubmed]
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