The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

STAT2  -  signal transducer and activator of...

Homo sapiens

Synonyms: ISGF-3, P113, STAT113, Signal transducer and activator of transcription 2, p113
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of STAT2


High impact information on STAT2


Chemical compound and disease context of STAT2


Biological context of STAT2


Anatomical context of STAT2

  • We have isolated U6A, a mutant cell line which lacks the STAT2 subunit of the transcription factor interferon (IFN)-stimulated gene factor 3 (ISGF3) [13].
  • Furthermore, the murine/human STAT2 protein was expressed in murine CD4(+) T cells and was activated by murine IFN-alpha signaling [16].
  • Interferons up-regulate STAT1, STAT2, and IRF family transcription factor gene expression in human peripheral blood mononuclear cells and macrophages [17].
  • In myeloid cells IFNalpha/beta activates signal transducers and activators of transcription STAT1, STAT2, and STAT3 [18].
  • However, during ATRA-induced differentiation, steady-state STAT1, STAT2, and especially p48 mRNA and corresponding protein levels were elevated both in NB4 and U937 cells, apparently correlating to an enhanced responsiveness of these cells to IFNs [19].

Associations of STAT2 with chemical compounds

  • In the present study, we show that ISGF3-mediated transcription is dependent on STAT2 interactions with DRIP150, a subunit of the multimeric Mediator coactivator complex [14].
  • Binding of type I interferons (IFNs) to their receptors induces rapid tyrosine phosphorylation of multiple proteins, including the alpha and beta subunits of the receptor, the polypeptides that form the transcriptional activator ISGF3 alpha (Stat113, Stat84, and Stat91), and the p135tyk2 and Jak-1 tyrosine kinases [20].
  • In this report we demonstrate that there are functionally redundant phosphotyrosine-dependent and -independent binding sites for Stat2 in the alpha and beta subunits of the type I IFN-R [21].
  • STAT2 export could be inhibited with leptomycin B, indicating a nuclear export signal within STAT2 is recognized by the CRM1 exportin carrier [22].
  • Induction of ISGF3 gamma but not of ISGF3 alpha needed ongoing protein synthesis and was blocked by 2-aminopurine [23].
  • This prolonged IFN response was associated with sustained tyrosine phosphorylation of STAT1 and STAT2 and their mutual association as heterodimers, which resulted from resistance to dephosphorylation by the nuclear tyrosine phosphatase TcPTP [24].

Physical interactions of STAT2


Enzymatic interactions of STAT2

  • Type I interferon (IFN) stimulates transcription through a heteromeric transcription factor that contains tyrosine-phosphorylated STAT2 [28].

Regulatory relationships of STAT2


Other interactions of STAT2

  • A complex containing p48 and phosphorylated STAT91 but lacking STAT113 bound the ISRE in vitro [32].
  • One is made up of STAT2, STAT4, and STAT6, which are activated by a small number of cytokines and play a distinct role in the development of T-cells and in IFNgamma signaling [33].
  • STAT1 and STAT2 mediate the antiviral and inflammatory effects of IFNalpha/beta, but the function of IFNalpha/beta-activated STAT3 is not known [18].
  • Members of the Rubulavirus genus of the Paramyxovirus family of RNA viruses have acquired the ability to specifically target either STAT1 or STAT2 for proteolytic degradation as a countermeasure for evading IFN responses [4].
  • Formation of STAT1-STAT2 heterodimers and their role in the activation of IRF-1 gene transcription by interferon-alpha [34].

Analytical, diagnostic and therapeutic context of STAT2


  1. Interferon-resistant human melanoma cells are deficient in ISGF3 components, STAT1, STAT2, and p48-ISGF3gamma. Wong, L.H., Krauer, K.G., Hatzinisiriou, I., Estcourt, M.J., Hersey, P., Tam, N.D., Edmondson, S., Devenish, R.J., Ralph, S.J. J. Biol. Chem. (1997) [Pubmed]
  2. Multiple NF-{kappa}B and IFN Regulatory Factor Family Transcription Factors Regulate CCL19 Gene Expression in Human Monocyte-Derived Dendritic Cells. Pietil??, T.E., Veckman, V., Lehtonen, A., Lin, R., Hiscott, J., Julkunen, I. J. Immunol. (2007) [Pubmed]
  3. A hybrid IRF9-STAT2 protein recapitulates interferon-stimulated gene expression and antiviral response. Kraus, T.A., Lau, J.F., Parisien, J.P., Horvath, C.M. J. Biol. Chem. (2003) [Pubmed]
  4. Selective STAT protein degradation induced by paramyxoviruses requires both STAT1 and STAT2 but is independent of alpha/beta interferon signal transduction. Parisien, J.P., Lau, J.F., Rodriguez, J.J., Ulane, C.M., Horvath, C.M. J. Virol. (2002) [Pubmed]
  5. Inhibition of interferon signaling by rabies virus phosphoprotein P: activation-dependent binding of STAT1 and STAT2. Brzózka, K., Finke, S., Conzelmann, K.K. J. Virol. (2006) [Pubmed]
  6. Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNgamma-mediated signaling. Zhu, M., John, S., Berg, M., Leonard, W.J. Cell (1999) [Pubmed]
  7. Use of an angiotensin II antagonist (saralasin) in the recognition of "angiotensinogenic" hypertension;. Streeten, D.H., Anderson, G.H., Freiberg, J.M., Dalakos, T.G. N. Engl. J. Med. (1975) [Pubmed]
  8. Cooperation of Stat2 and p300/CBP in signalling induced by interferon-alpha. Bhattacharya, S., Eckner, R., Grossman, S., Oldread, E., Arany, Z., D'Andrea, A., Livingston, D.M. Nature (1996) [Pubmed]
  9. Direct stimulation of Jak/STAT pathway by the angiotensin II AT1 receptor. Marrero, M.B., Schieffer, B., Paxton, W.G., Heerdt, L., Berk, B.C., Delafontaine, P., Bernstein, K.E. Nature (1995) [Pubmed]
  10. Differential recognition of the type I interferon receptor by interferons tau and alpha is responsible for their disparate cytotoxicities. Subramaniam, P.S., Khan, S.A., Pontzer, C.H., Johnson, H.M. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  11. Stat1 is induced and activated by all-trans retinoic acid in acute promyelocytic leukemia cells. Gianni, M., Terao, M., Fortino, I., LiCalzi, M., Viggiano, V., Barbui, T., Rambaldi, A., Garattini, E. Blood (1997) [Pubmed]
  12. Blockade and stimulation of renal, adrenal, and vascular angiotensin II receptors with 1-Sar, 8-Ala angiotensin II in normal man. Hollenberg, N.K., Williams, G.H., Burger, B., Ishikawa, I., Adams, D.F. J. Clin. Invest. (1976) [Pubmed]
  13. Role of STAT2 in the alpha interferon signaling pathway. Leung, S., Qureshi, S.A., Kerr, I.M., Darnell, J.E., Stark, G.R. Mol. Cell. Biol. (1995) [Pubmed]
  14. Role of metazoan mediator proteins in interferon-responsive transcription. Lau, J.F., Nusinzon, I., Burakov, D., Freedman, L.P., Horvath, C.M. Mol. Cell. Biol. (2003) [Pubmed]
  15. Arginine/lysine-rich structural element is involved in interferon-induced nuclear import of STATs. Melen, K., Kinnunen, L., Julkunen, I. J. Biol. Chem. (2001) [Pubmed]
  16. IL-12, but not IFN-alpha, promotes STAT4 activation and Th1 development in murine CD4+ T cells expressing a chimeric murine/human Stat2 gene. Persky, M.E., Murphy, K.M., Farrar, J.D. J. Immunol. (2005) [Pubmed]
  17. Interferons up-regulate STAT1, STAT2, and IRF family transcription factor gene expression in human peripheral blood mononuclear cells and macrophages. Lehtonen, A., Matikainen, S., Julkunen, I. J. Immunol. (1997) [Pubmed]
  18. Role of STAT3 in type I interferon responses. Negative regulation of STAT1-dependent inflammatory gene activation. Ho, H.H., Ivashkiv, L.B. J. Biol. Chem. (2006) [Pubmed]
  19. Retinoic acid induces signal transducer and activator of transcription (STAT) 1, STAT2, and p48 expression in myeloid leukemia cells and enhances their responsiveness to interferons. Matikainen, S., Ronni, T., Lehtonen, A., Sareneva, T., Melén, K., Nordling, S., Levy, D.E., Julkunen, I. Cell Growth Differ. (1997) [Pubmed]
  20. Direct binding to and tyrosine phosphorylation of the alpha subunit of the type I interferon receptor by p135tyk2 tyrosine kinase. Colamonici, O., Yan, H., Domanski, P., Handa, R., Smalley, D., Mullersman, J., Witte, M., Krishnan, K., Krolewski, J. Mol. Cell. Biol. (1994) [Pubmed]
  21. The proximal tyrosines of the cytoplasmic domain of the beta chain of the type I interferon receptor are essential for signal transducer and activator of transcription (Stat) 2 activation. Evidence that two Stat2 sites are required to reach a threshold of interferon alpha-induced Stat2 tyrosine phosphorylation that allows normal formation of interferon-stimulated gene factor 3. Nadeau, O.W., Domanski, P., Usacheva, A., Uddin, S., Platanias, L.C., Pitha, P., Raz, R., Levy, D., Majchrzak, B., Fish, E., Colamonici, O.R. J. Biol. Chem. (1999) [Pubmed]
  22. STAT2 nuclear trafficking. Banninger, G., Reich, N.C. J. Biol. Chem. (2004) [Pubmed]
  23. Gene induction by interferons: functional complementation between trans-acting factors induced by alpha interferon and gamma interferon. Bandyopadhyay, S.K., Kalvakolanu, D.V., Sen, G.C. Mol. Cell. Biol. (1990) [Pubmed]
  24. A Mutation in the SH2 domain of STAT2 prolongs tyrosine phosphorylation of STAT1 and promotes type I IFN-induced apoptosis. Scarzello, A.J., Romero-Weaver, A.L., Maher, S.G., Veenstra, T.D., Zhou, M., Qin, A., Donnelly, R.P., Sheikh, F., Gamero, A.M. Mol. Biol. Cell (2007) [Pubmed]
  25. Distinct STAT structure promotes interaction of STAT2 with the p48 subunit of the interferon-alpha-stimulated transcription factor ISGF3. Martinez-Moczygemba, M., Gutch, M.J., French, D.L., Reich, N.C. J. Biol. Chem. (1997) [Pubmed]
  26. Application of genomic DNA affinity chromatography identifies multiple interferon-alpha-regulated Stat2 complexes. Ghislain, J.J., Fish, E.N. J. Biol. Chem. (1996) [Pubmed]
  27. Functional subdomains of STAT2 required for preassociation with the alpha interferon receptor and for signaling. Li, X., Leung, S., Kerr, I.M., Stark, G.R. Mol. Cell. Biol. (1997) [Pubmed]
  28. IFN-Stimulated transcription through a TBP-free acetyltransferase complex escapes viral shutoff. Paulson, M., Press, C., Smith, E., Tanese, N., Levy, D.E. Nat. Cell Biol. (2002) [Pubmed]
  29. Interferon regulatory factor subcellular localization is determined by a bipartite nuclear localization signal in the DNA-binding domain and interaction with cytoplasmic retention factors. Lau, J.F., Parisien, J.P., Horvath, C.M. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  30. Recruitment of Stat4 to the human interferon-alpha/beta receptor requires activated Stat2. Farrar, J.D., Smith, J.D., Murphy, T.L., Murphy, K.M. J. Biol. Chem. (2000) [Pubmed]
  31. EGF induces nuclear translocation of STAT2 without tyrosine phosphorylation in intestinal epithelial cells. Johnson, L.R., McCormack, S.A., Yang, C.H., Pfeffer, S.R., Pfeffer, L.M. Am. J. Physiol. (1999) [Pubmed]
  32. Combinatorial association and abundance of components of interferon-stimulated gene factor 3 dictate the selectivity of interferon responses. Bluyssen, H.A., Muzaffar, R., Vlieststra, R.J., van der Made, A.C., Leung, S., Stark, G.R., Kerr, I.M., Trapman, J., Levy, D.E. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  33. STAT proteins: from normal control of cellular events to tumorigenesis. Calò, V., Migliavacca, M., Bazan, V., Macaluso, M., Buscemi, M., Gebbia, N., Russo, A. J. Cell. Physiol. (2003) [Pubmed]
  34. Formation of STAT1-STAT2 heterodimers and their role in the activation of IRF-1 gene transcription by interferon-alpha. Li, X., Leung, S., Qureshi, S., Darnell, J.E., Stark, G.R. J. Biol. Chem. (1996) [Pubmed]
  35. Dominant negative signal transducer and activator of transcription 2 (STAT2) protein: stable expression blocks interferon alpha action in skin squamous cell carcinoma cells. Clifford, J.L., Yang, X., Walch, E., Wang, M., Lippman, S.M. Mol. Cancer Ther. (2003) [Pubmed]
  36. Global changes in STAT target selection and transcription regulation upon interferon treatments. Hartman, S.E., Bertone, P., Nath, A.K., Royce, T.E., Gerstein, M., Weissman, S., Snyder, M. Genes Dev. (2005) [Pubmed]
  37. Importin alpha nuclear localization signal binding sites for STAT1, STAT2, and influenza A virus nucleoprotein. Melen, K., Fagerlund, R., Franke, J., Kohler, M., Kinnunen, L., Julkunen, I. J. Biol. Chem. (2003) [Pubmed]
  38. Detection of the genes induced in activated lymphocytes by modified differential display. Kaneko, H., Inoue, R., Teramoto, T., Morimoto, W., Isogai, K., Kasahara, K., Kondo, N. Journal of investigational allergology & clinical immunology : official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología. (2002) [Pubmed]
WikiGenes - Universities