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Gene Review

Stat4  -  signal transducer and activator of...

Mus musculus

Synonyms: Signal transducer and activator of transcription 4
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Disease relevance of Stat4

  • Thus, Stat6-/- and Stat4-/- mice appeared to be resistant to septic peritonitis by enhancing local bacterial clearance and modulating systemic organ damage, respectively, via balancing cytokine responses [1].
  • In Stat4-/- mice, hepatic inflammation and injury during sepsis were significantly ameliorated without affecting local responses [1].
  • Specifically, Stat4-deficient NZM mice develop accelerated nephritis and increased mortality in the absence of high levels of autoantibodies including anti-dsDNA Abs, and in the presence of relatively reduced levels of IFN-gamma [2].
  • While infected Stat4-deficient mice developed pulmonary granulomas following schistosome egg injection that were modestly impaired in size, the granuloma size and amount of collagen deposition in the liver were equivalent to those seen in control littermates [3].
  • Stat4-null non-obese diabetic mice: protection from diabetes and experimental allergic encephalomyelitis, but with concomitant epitope spread [4].

High impact information on Stat4


Chemical compound and disease context of Stat4


Biological context of Stat4


Anatomical context of Stat4


Associations of Stat4 with chemical compounds


Regulatory relationships of Stat4

  • Stat4 regulates multiple components of IFN-gamma-inducing signaling pathways [10].
  • To explore changes in HPC responsiveness in altered T helper cell environments, we directly examined growth factor-stimulated colony formation and chemokine-induced myelosuppression of HPC in Stat4- and Stat6-deficient bone marrow cells [18].
  • Increased susceptibility of Stat4-deficient and enhanced resistance in Stat6-deficient mice to infection with Trypanosoma cruzi [19].

Other interactions of Stat4

  • Antiserum to Stat3 detects a major approximately 92-kDa protein and a minor approximately 89-kDa protein, while antiserum to Stat4 precipitates one major protein of approximately 89 kDa [20].
  • Therefore, Stat1 and Stat4 independently play substantial roles in the susceptibility to LPS [21].
  • We have shown that transcription of signal transducer and activator of transcription 4 (Stat4) plays a key role in the mechanism of hepatic IRI, whereas local induction of interleukin 13 (IL-13) is cytoprotective [22].
  • Mice in which the genes for Stat4 and Stat6 are disrupted are viable but lack functions that are mediated by interleukin 12 (IL-12) or IL-4, respectively, suggesting that these Stats perform very specific functions in immune responses [23].
  • This is due to defective IL-18 signaling, which results from the lack of IL-12-induced, and Stat4-dependent, expression of the IL-18R [10].

Analytical, diagnostic and therapeutic context of Stat4


  1. Pivotal role of signal transducer and activator of transcription (Stat)4 and Stat6 in the innate immune response during sepsis. Matsukawa, A., Kaplan, M.H., Hogaboam, C.M., Lukacs, N.W., Kunkel, S.L. J. Exp. Med. (2001) [Pubmed]
  2. Pivotal role of Stat4 and Stat6 in the pathogenesis of the lupus-like disease in the New Zealand mixed 2328 mice. Jacob, C.O., Zang, S., Li, L., Ciobanu, V., Quismorio, F., Mizutani, A., Satoh, M., Koss, M. J. Immunol. (2003) [Pubmed]
  3. Th2 cells are required for the Schistosoma mansoni egg-induced granulomatous response. Kaplan, M.H., Whitfield, J.R., Boros, D.L., Grusby, M.J. J. Immunol. (1998) [Pubmed]
  4. Stat4-null non-obese diabetic mice: protection from diabetes and experimental allergic encephalomyelitis, but with concomitant epitope spread. Boyton, R.J., Davies, S., Marden, C., Fantino, C., Reynolds, C., Portugal, K., Dewchand, H., Altmann, D.M. Int. Immunol. (2005) [Pubmed]
  5. Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice. Kaplan, M.H., Sun, Y.L., Hoey, T., Grusby, M.J. Nature (1996) [Pubmed]
  6. GATA-3 suppresses Th1 development by downregulation of Stat4 and not through effects on IL-12Rbeta2 chain or T-bet. Usui, T., Nishikomori, R., Kitani, A., Strober, W. Immunity (2003) [Pubmed]
  7. Effect of targeted disruption of signal transducer and activator of transcription (Stat)4 and Stat6 genes on the autoimmune diabetes development induced by multiple low doses of streptozotocin. Cetkovic-Cvrlje, M., Uckun, F.M. Clin. Immunol. (2005) [Pubmed]
  8. Dysfunction of Stat4 leads to accelerated incidence of chemical-induced thymic lymphomas in mice. Zhang, S.S., Welte, T., Fu, X.Y. Exp. Mol. Pathol. (2001) [Pubmed]
  9. Stat4 and Stat6 signaling in hepatic ischemia/reperfusion injury in mice: HO-1 dependence of Stat4 disruption-mediated cytoprotection. Shen, X.D., Ke, B., Zhai, Y., Gao, F., Anselmo, D., Lassman, C.R., Busuttil, R.W., Kupiec-Weglinski, J.W. Hepatology (2003) [Pubmed]
  10. Stat4 regulates multiple components of IFN-gamma-inducing signaling pathways. Lawless, V.A., Zhang, S., Ozes, O.N., Bruns, H.A., Oldham, I., Hoey, T., Grusby, M.J., Kaplan, M.H. J. Immunol. (2000) [Pubmed]
  11. Th1 cells regulate hematopoietic progenitor cell homeostasis by production of oncostatin M. Broxmeyer, H.E., Bruns, H.A., Zhang, S., Cooper, S., Hangoc, G., McKenzie, A.N., Dent, A.L., Schindler, U., Naeger, L.K., Hoey, T., Kaplan, M.H. Immunity (2002) [Pubmed]
  12. Involvement of connective tissue-type mast cells in Th1 immune responses via Stat4 expression. Kataoka, T.R., Komazawa, N., Morii, E., Oboki, K., Nakano, T. Blood (2005) [Pubmed]
  13. A signal transducer and activator of transcription (Stat)4-independent pathway for the development of T helper type 1 cells. Kaplan, M.H., Wurster, A.L., Grusby, M.J. J. Exp. Med. (1998) [Pubmed]
  14. Interleukin 12 signaling in T helper type 1 (Th1) cells involves tyrosine phosphorylation of signal transducer and activator of transcription (Stat)3 and Stat4. Jacobson, N.G., Szabo, S.J., Weber-Nordt, R.M., Zhong, Z., Schreiber, R.D., Darnell, J.E., Murphy, K.M. J. Exp. Med. (1995) [Pubmed]
  15. Cutting edge: differential requirements for Stat4 in expression of glycosyltransferases responsible for selectin ligand formation in Th1 cells. White, S.J., Underhill, G.H., Kaplan, M.H., Kansas, G.S. J. Immunol. (2001) [Pubmed]
  16. Unexpected characteristics of the IFN-gamma reporters in nontransformed T cells. Zhu, H., Yang, J., Murphy, T.L., Ouyang, W., Wagner, F., Saparov, A., Weaver, C.T., Murphy, K.M. J. Immunol. (2001) [Pubmed]
  17. The p38 mitogen-activated protein kinase is required for IL-12-induced IFN-gamma expression. Zhang, S., Kaplan, M.H. J. Immunol. (2000) [Pubmed]
  18. Distinct requirements for Stat4 and Stat6 in hematopoietic progenitor cell responses to growth factors and chemokines. Kaplan, M.H., Chang, H.C., Cooper, S., Lee, Y., Broxmeyer, H.E. J. Hematother. Stem Cell Res. (2003) [Pubmed]
  19. Increased susceptibility of Stat4-deficient and enhanced resistance in Stat6-deficient mice to infection with Trypanosoma cruzi. Tarleton, R.L., Grusby, M.J., Zhang, L. J. Immunol. (2000) [Pubmed]
  20. Stat3 and Stat4: members of the family of signal transducers and activators of transcription. Zhong, Z., Wen, Z., Darnell, J.E. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  21. The role of Tyk2, Stat1 and Stat4 in LPS-induced endotoxin signals. Kamezaki, K., Shimoda, K., Numata, A., Matsuda, T., Nakayama, K., Harada, M. Int. Immunol. (2004) [Pubmed]
  22. Interleukin 13 gene transfer in liver ischemia and reperfusion injury: role of Stat6 and TLR4 pathways in cytoprotection. Ke, B., Shen, X.D., Gao, F., Busuttil, R.W., Kupiec-Weglinski, J.W. Hum. Gene Ther. (2004) [Pubmed]
  23. Jaks and Stats in cytokine signaling. Ihle, J.N., Nosaka, T., Thierfelder, W., Quelle, F.W., Shimoda, K. Stem Cells (1997) [Pubmed]
  24. Distinct requirements for the naturally occurring splice forms Stat4alpha and Stat4beta in IL-12 responses. Hoey, T., Zhang, S., Schmidt, N., Yu, Q., Ramchandani, S., Xu, X., Naeger, L.K., Sun, Y.L., Kaplan, M.H. EMBO J. (2003) [Pubmed]
  25. The mouse transcription factor Stat4 is expressed in haploid male germ cells and is present in the perinuclear theca of spermatozoa. Herrada, G., Wolgemuth, D.J. J. Cell. Sci. (1997) [Pubmed]
  26. Role of Stat4-Mediated Signal Transduction Events in the Generation of Aggressor CD4(+) T Cells in Herpetic Stromal Keratitis Pathogenesis. Banerjee, K., Biswas, P.S., Rouse, B.T. J. Interferon Cytokine Res. (2007) [Pubmed]
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