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. 1994 May 24;91(11):4806–4810. doi: 10.1073/pnas.91.11.4806

Stat3 and Stat4: members of the family of signal transducers and activators of transcription.

Z Zhong 1, Z Wen 1, J E Darnell Jr 1
PMCID: PMC43877  PMID: 7545930

Abstract

The deduced amino acid sequence of two members of the signal transducers and activators of transcription (STAT) family from the mouse are described. Comparison with the deduced protein sequence of the two previously described genes (Stat91 and Stat113), discovered because of their activation as transcription factors after interferon-induced tyrosine phosphorylation, shows several highly conserved regions, including the putative SH3 and SH2 domains. The conserved amino acid stretches likely point to conserved domains that enable these proteins to carry out the several required functions they are known and proposed to carry out. While Stat1 and Stat3 are widely expressed, Stat4 expression is restricted to testis, thymus, and spleen. 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.

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Selected References

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  1. Bonni A., Frank D. A., Schindler C., Greenberg M. E. Characterization of a pathway for ciliary neurotrophic factor signaling to the nucleus. Science. 1993 Dec 3;262(5139):1575–1579. doi: 10.1126/science.7504325. [DOI] [PubMed] [Google Scholar]
  2. Cantley L. C., Auger K. R., Carpenter C., Duckworth B., Graziani A., Kapeller R., Soltoff S. Oncogenes and signal transduction. Cell. 1991 Jan 25;64(2):281–302. doi: 10.1016/0092-8674(91)90639-g. [DOI] [PubMed] [Google Scholar]
  3. Church G. M., Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. doi: 10.1073/pnas.81.7.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fu X. Y., Zhang J. J. Transcription factor p91 interacts with the epidermal growth factor receptor and mediates activation of the c-fos gene promoter. Cell. 1993 Sep 24;74(6):1135–1145. doi: 10.1016/0092-8674(93)90734-8. [DOI] [PubMed] [Google Scholar]
  5. Kanno Y., Kozak C. A., Schindler C., Driggers P. H., Ennist D. L., Gleason S. L., Darnell J. E., Jr, Ozato K. The genomic structure of the murine ICSBP gene reveals the presence of the gamma interferon-responsive element, to which an ISGF3 alpha subunit (or similar) molecule binds. Mol Cell Biol. 1993 Jul;13(7):3951–3963. doi: 10.1128/mcb.13.7.3951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Koch C. A., Anderson D., Moran M. F., Ellis C., Pawson T. SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins. Science. 1991 May 3;252(5006):668–674. doi: 10.1126/science.1708916. [DOI] [PubMed] [Google Scholar]
  7. Kotanides H., Reich N. C. Requirement of tyrosine phosphorylation for rapid activation of a DNA binding factor by IL-4. Science. 1993 Nov 19;262(5137):1265–1267. doi: 10.1126/science.7694370. [DOI] [PubMed] [Google Scholar]
  8. Kozak M. Regulation of protein synthesis in virus-infected animal cells. Adv Virus Res. 1986;31:229–292. doi: 10.1016/S0065-3527(08)60265-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Larner A. C., David M., Feldman G. M., Igarashi K., Hackett R. H., Webb D. S., Sweitzer S. M., Petricoin E. F., 3rd, Finbloom D. S. Tyrosine phosphorylation of DNA binding proteins by multiple cytokines. Science. 1993 Sep 24;261(5129):1730–1733. doi: 10.1126/science.8378773. [DOI] [PubMed] [Google Scholar]
  10. Levy D., Darnell J. E., Jr Interferon-dependent transcriptional activation: signal transduction without second messenger involvement? New Biol. 1990 Oct;2(10):923–928. [PubMed] [Google Scholar]
  11. Lew D. J., Decker T., Strehlow I., Darnell J. E. Overlapping elements in the guanylate-binding protein gene promoter mediate transcriptional induction by alpha and gamma interferons. Mol Cell Biol. 1991 Jan;11(1):182–191. doi: 10.1128/mcb.11.1.182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Müller M., Laxton C., Briscoe J., Schindler C., Improta T., Darnell J. E., Jr, Stark G. R., Kerr I. M. Complementation of a mutant cell line: central role of the 91 kDa polypeptide of ISGF3 in the interferon-alpha and -gamma signal transduction pathways. EMBO J. 1993 Nov;12(11):4221–4228. doi: 10.1002/j.1460-2075.1993.tb06106.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Pearse R. N., Feinman R., Shuai K., Darnell J. E., Jr, Ravetch J. V. Interferon gamma-induced transcription of the high-affinity Fc receptor for IgG requires assembly of a complex that includes the 91-kDa subunit of transcription factor ISGF3. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4314–4318. doi: 10.1073/pnas.90.9.4314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ren R., Mayer B. J., Cicchetti P., Baltimore D. Identification of a ten-amino acid proline-rich SH3 binding site. Science. 1993 Feb 19;259(5098):1157–1161. doi: 10.1126/science.8438166. [DOI] [PubMed] [Google Scholar]
  15. Ruff-Jamison S., Chen K., Cohen S. Induction by EGF and interferon-gamma of tyrosine phosphorylated DNA binding proteins in mouse liver nuclei. Science. 1993 Sep 24;261(5129):1733–1736. doi: 10.1126/science.8378774. [DOI] [PubMed] [Google Scholar]
  16. Sadowski H. B., Shuai K., Darnell J. E., Jr, Gilman M. Z. A common nuclear signal transduction pathway activated by growth factor and cytokine receptors. Science. 1993 Sep 24;261(5129):1739–1744. doi: 10.1126/science.8397445. [DOI] [PubMed] [Google Scholar]
  17. Schindler C., Fu X. Y., Improta T., Aebersold R., Darnell J. E., Jr Proteins of transcription factor ISGF-3: one gene encodes the 91-and 84-kDa ISGF-3 proteins that are activated by interferon alpha. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7836–7839. doi: 10.1073/pnas.89.16.7836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Shuai K., Horvath C. M., Huang L. H., Qureshi S. A., Cowburn D., Darnell J. E., Jr Interferon activation of the transcription factor Stat91 involves dimerization through SH2-phosphotyrosyl peptide interactions. Cell. 1994 Mar 11;76(5):821–828. doi: 10.1016/0092-8674(94)90357-3. [DOI] [PubMed] [Google Scholar]
  19. Shuai K., Stark G. R., Kerr I. M., Darnell J. E., Jr A single phosphotyrosine residue of Stat91 required for gene activation by interferon-gamma. Science. 1993 Sep 24;261(5129):1744–1746. doi: 10.1126/science.7690989. [DOI] [PubMed] [Google Scholar]
  20. Shuai K., Ziemiecki A., Wilks A. F., Harpur A. G., Sadowski H. B., Gilman M. Z., Darnell J. E. Polypeptide signalling to the nucleus through tyrosine phosphorylation of Jak and Stat proteins. Nature. 1993 Dec 9;366(6455):580–583. doi: 10.1038/366580a0. [DOI] [PubMed] [Google Scholar]
  21. Silvennoinen O., Schindler C., Schlessinger J., Levy D. E. Ras-independent growth factor signaling by transcription factor tyrosine phosphorylation. Science. 1993 Sep 24;261(5129):1736–1739. doi: 10.1126/science.8378775. [DOI] [PubMed] [Google Scholar]
  22. Waksman G., Shoelson S. E., Pant N., Cowburn D., Kuriyan J. Binding of a high affinity phosphotyrosyl peptide to the Src SH2 domain: crystal structures of the complexed and peptide-free forms. Cell. 1993 Mar 12;72(5):779–790. doi: 10.1016/0092-8674(93)90405-f. [DOI] [PubMed] [Google Scholar]

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