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Gene Review

Stat3  -  signal transducer and activator of...

Rattus norvegicus

Synonyms: Signal transducer and activator of transcription 3
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Disease relevance of Stat3


High impact information on Stat3

  • A two-step event is suggested for APRF/Stat3-dependent gene activation in hepatocytes [6].
  • GRIM-19, a gene product related to interferon-beta- and retinoic acid-induced cancer cell death, was identified and demonstrated to interact with Stat3 in various cell types [7].
  • Stat3 plays important roles in cell growth, anti-apoptosis and cell transformation, and is constitutively active in various cancers [7].
  • Immunoreactive Jak2, Tyk2, Stat1, and Stat3 were not detected in the intact artery [8].
  • Furthermore, local treatment with AG490 inhibited constitutive Stat3 phosphorylation and neointimal VSMC replication and subsequently reduced neointima formation in the injured artery [8].

Chemical compound and disease context of Stat3


Biological context of Stat3


Anatomical context of Stat3

  • In vivo, Stat3 activation was dramatically suppressed by depletion of neutrophils or lung macrophages, resulting in reduced gene expression of IL-6 and IL-10 in whole lung tissues [2].
  • These data suggest in the lung injury model used that activation of Stat3 in lungs is macrophage dependent and neutrophil dependent [2].
  • We now show that Stat3 activation was triggered in lungs and in alveolar macrophages after intrapulmonary deposition of IgG immune complexes in rats [2].
  • Expression of all Stat3 mutants had no effect on NGF-induced neurite outgrowth [12].
  • In contrast, granulosa cells of untreated immature and H rats contained a high level of DNA binding activity, which was shown to be comprised entirely of activated, phosphorylated Stat3 [13].

Associations of Stat3 with chemical compounds


Physical interactions of Stat3


Enzymatic interactions of Stat3

  • RGCs as well as native retina expressed functional IL-10R as determined by immunoblot analysis and by the ability of IL-10 to phosphorylate Stat-3 [18].

Regulatory relationships of Stat3

  • Purified APRE binding factors (APRFs) from IL-6-stimulated rat liver were found to be composed of multiple Stat3-related proteins and Stat1 [19].

Other interactions of Stat3

  • Amino acid sequence analysis identified the 86- and 91-kDa species as two forms of the transcription factor Stat3 and the 92-kDa species as the factor Stat5b [1].
  • Here we examine the activation of Stat1 and Stat3 in rat astrocyte cultures and its involvement in cell death [15].
  • Collectively, these results indicate that Stat3 and Stat5 are activated by distinct cytokine-signaling pathways modulated through differentiation-dependent transcriptional regulation of signaling pathway components and mediate distinct functional processes in the rat ovary: early follicle growth and atresia vs. luteinization [13].
  • These results suggest, that APRF/Stat3 and p91/Stat1 are not the only factors mediating the effects of IL-6 on class 2 acute phase genes [20].
  • RESULTS: Shock animals demonstrated increased mRNA levels of interleukin (IL)-6 and intercellular adhesion molecule (ICAM)-1 and increased activation of the transcription factors nuclear factor kappa B (NF-kappa B) and signal transducers and activators of transcription 3 (Stat3) [21].

Analytical, diagnostic and therapeutic context of Stat3


  1. Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. Ripperger, J.A., Fritz, S., Richter, K., Hocke, G.M., Lottspeich, F., Fey, G.H. J. Biol. Chem. (1995) [Pubmed]
  2. Stat3 activation in acute lung injury. Gao, H., Guo, R.F., Speyer, C.L., Reuben, J., Neff, T.A., Hoesel, L.M., Riedemann, N.C., McClintock, S.D., Sarma, J.V., Van Rooijen, N., Zetoune, F.S., Ward, P.A. J. Immunol. (2004) [Pubmed]
  3. Suppression of Stat3 promotes neurogenesis in cultured neural stem cells. Gu, F., Hata, R., Ma, Y.J., Tanaka, J., Mitsuda, N., Kumon, Y., Hanakawa, Y., Hashimoto, K., Nakajima, K., Sakanaka, M. J. Neurosci. Res. (2005) [Pubmed]
  4. Activation of signal transducer and activator of transcription-3 (Stat3) expression by interferon-gamma and interleukin-6 in hepatoma cells. Kordula, T., Bugno, M., Goldstein, J., Travis, J. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  5. 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]
  6. Acute-phase response factor, increased binding, and target gene transcription during liver regeneration. Trautwein, C., Rakemann, T., Niehof, M., Rose-John, S., Manns, M.P. Gastroenterology (1996) [Pubmed]
  7. GRIM-19, a death-regulatory gene product, suppresses Stat3 activity via functional interaction. Lufei, C., Ma, J., Huang, G., Zhang, T., Novotny-Diermayr, V., Ong, C.T., Cao, X. EMBO J. (2003) [Pubmed]
  8. Role of the JAK/STAT pathway in rat carotid artery remodeling after vascular injury. Seki, Y., Kai, H., Shibata, R., Nagata, T., Yasukawa, H., Yoshimura, A., Imaizumi, T. Circ. Res. (2000) [Pubmed]
  9. c-PKC-dependent modulation of plasma fibrinogen levels during the acute-phase response in young and old rats. La Porta, C.A., Franchi, C., Comolli, R. Mech. Ageing Dev. (1998) [Pubmed]
  10. 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]
  11. Rapid activation of the Stat3 transcription complex in liver regeneration. Cressman, D.E., Diamond, R.H., Taub, R. Hepatology (1995) [Pubmed]
  12. Activation of the Stat3 signaling pathway is required for differentiation by interleukin-6 in PC12-E2 cells. Wu, Y.Y., Bradshaw, R.A. J. Biol. Chem. (2000) [Pubmed]
  13. Differentiation-dependent prolactin responsiveness and stat (signal transducers and activators of transcription) signaling in rat ovarian cells. Russell, D.L., Richards, J.S. Mol. Endocrinol. (1999) [Pubmed]
  14. Two discrete regions of interleukin-2 (IL2) receptor beta independently mediate IL2 activation of a PD98059/rapamycin/wortmannin-insensitive Stat5a/b serine kinase. Kirken, R.A., Malabarba, M.G., Xu, J., DaSilva, L., Erwin, R.A., Liu, X., Hennighausen, L., Rui, H., Farrar, W.L. J. Biol. Chem. (1997) [Pubmed]
  15. 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]
  16. Angiotensin II activates Stat5 through Jak2 kinase in cardiac myocytes. McWhinney, C.D., Dostal, D., Baker, K. J. Mol. Cell. Cardiol. (1998) [Pubmed]
  17. The vagus nerve mediates behavioural depression, but not fever, in response to peripheral immune signals; a functional anatomical analysis. Konsman, J.P., Luheshi, G.N., Bluthé, R.M., Dantzer, R. Eur. J. Neurosci. (2000) [Pubmed]
  18. Interleukin-10 receptor signaling through STAT-3 regulates the apoptosis of retinal ganglion cells in response to stress. Boyd, Z.S., Kriatchko, A., Yang, J., Agarwal, N., Wax, M.B., Patil, R.V. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
  19. Transcriptional activation of the IL-6 response element in the junB promoter is mediated by multiple Stat family proteins. Fujitani, Y., Nakajima, K., Kojima, H., Nakae, K., Takeda, T., Hirano, T. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  20. Isolation of two interleukin-6 response element binding proteins from acute phase rat livers. Ripperger, J., Fritz, S., Richter, K., Dreier, B., Schneider, K., Löchner, K., Marschalek, R., Hocke, G., Lottspeich, F., Fey, G.H. Ann. N. Y. Acad. Sci. (1995) [Pubmed]
  21. Reduced hepatic transcription factor activation and expression of IL-6 and ICAM-1 after hemorrhage by NO scavenging. Hierholzer, C., Billiar, T.R., Tweardy, D.J., Harbrecht, B. Archives of orthopaedic and trauma surgery. (2003) [Pubmed]
  22. After portal branch ligation in rat, nuclear factor kappaB, interleukin-6, signal transducers and activators of transcription 3, c-fos, c-myc, and c-jun are similarly induced in the ligated and nonligated lobes. Stärkel, P., Horsmans, Y., Sempoux, C., De Saeger, C., Wary, J., Lause, P., Maiter, D., Lambotte, L. Hepatology (1999) [Pubmed]
  23. In vivo growth hormone treatment rapidly stimulates the tyrosine phosphorylation and activation of Stat3. Gronowski, A.M., Zhong, Z., Wen, Z., Thomas, M.J., Darnell, J.E., Rotwein, P. Mol. Endocrinol. (1995) [Pubmed]
  24. Molecular and functional contractile sequelae of rat intestinal ischemia/reperfusion injury. Hierholzer, C., Kalff, J.C., Audolfsson, G., Billiar, T.R., Tweardy, D.J., Bauer, A.J. Transplantation (1999) [Pubmed]
  25. Phosphorylation of signal transducer and activator of transcription-3 (Stat3) after focal cerebral ischemia in rats. Suzuki, S., Tanaka, K., Nogawa, S., Dembo, T., Kosakai, A., Fukuuchi, Y. Exp. Neurol. (2001) [Pubmed]
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