Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Functional interactions between Stat5 and the glucocorticoid receptor

Nature volume 383, pages 726–728 (1996)Cite this article

Abstract

SIGNAL transduction pathways enable extracellular signals to activate latent transcription factors in the cytoplasm of cells. Dimerization, nuclear localization and binding to specific DNA sequences result in the induction of gene transcription by these proteins. These events are necessary for the functioning of the JAK/STAT pathway and of the glucocorticoid-receptor pathway. In the former, the protein Stat5, which is a member of a family of signal transducers and activators of transcription, is activated by cytokines, hormones and growth factors1–7. These polypeptide ligands bind at the outside of the cell to specific transmembrane receptors and activate intracellular Janus protein tyrosine kinases (JAKs) to tyrosine-phosphorylate STAT proteins; interaction with the SH2 domain of the dimerization partner then confers the ability to bind to DNA at the STAT-response element and induce transcription8–10. In the glucocorticoid-receptor path-way, the receptor interacts with its steroid hormone ligand in the cytoplasm, undergoes an allosteric change that enables the hormone receptor complex to bind to specific DNA-response elements (glucocorticoid response elements, or GRE) and mod-ulate transcription11,12. Although these pathways appear to be unrelated, we show here that the glucocorticoid receptor can act as a transcriptional co-activator for Stat5 and enhance Stat5-dependent transcription. Stat5 forms a complex with the gluco-corticoid receptor which binds to DNA independently of the GRE. This complex formation between Stat5 and the glucocorticoid receptor diminishes the glucocorticoid response of a GRE-con-taining promoter.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

References

  1. Azam, M. et al. EMBO J. 14, 1402–1411 (1995).

    CAS  Article  Google Scholar 

  2. Fuji, H. et al. Proc. Natl Acad. Sci. USA 92, 5482–5486 (1995).

    ADS  Article  Google Scholar 

  3. Gouilleux, F. et al. Endocrinol. 136, 5700–5708 (1995).

    CAS  Article  Google Scholar 

  4. Gouilleux, F. et al. EMBO J. 14, 2005–2013 (1995).

    CAS  Article  Google Scholar 

  5. Mui, A., Wakao, H., O'Farrell, A. M., Harada, N. & Miyajima, A. EMBO J. 14, 1166–1175 (1995).

    CAS  Article  Google Scholar 

  6. Pallard, C. et al. EMBO J. 14, 2847–2856 (1995).

    CAS  Article  Google Scholar 

  7. Yoshimura, A. et al. EMBO J. 15, 1055–1063 (1996).

    CAS  Article  Google Scholar 

  8. Darnell, J. E., Kerr, I. M. & Stark, G. R. Science 264, 1415–1421 (1994).

    ADS  CAS  Article  Google Scholar 

  9. Ihle, J. N. Nature 377, 591–594 (1995).

    ADS  CAS  Article  Google Scholar 

  10. Ihle, J. N. Cell 84, 331–334 (1996).

    CAS  Article  Google Scholar 

  11. Beato, M., Herrlich, P. & Schütz, G. Cell 83, 851–857 (1995).

    CAS  Article  Google Scholar 

  12. Mangelsdorf, D. J. et al. Cell 83, 835–839 (1995).

    CAS  Article  Google Scholar 

  13. Schmitt-Ney, M., Doppler, W., Ball, R. K. & Groner, B. Mol. Cell. Biol. 11, 3745–3755 (1991).

    CAS  Article  Google Scholar 

  14. Schmitt-Ney, M., Happ, B., Ball, R. & Groner, B. Proc. Natl Acad. Sci. USA 89, 3130–3134 (1992).

    ADS  CAS  Article  Google Scholar 

  15. Wakao, H., Gouilleux, F. & Groner, B. EMBO J. 13, 2182–2191 (1994).

    CAS  Article  Google Scholar 

  16. Höck, W. & Groner, B. J. Biol. Chem. 265, 5403–5408 (1990).

    Google Scholar 

  17. Lebrun, J.-J., Ali, S., Goffin, V., Ullrich, A. & Kelly, P. Proc. Natl Acad. Sci. USA 92, 4031–4035 (1995).

    ADS  CAS  Article  Google Scholar 

  18. Gouilleux, F., Wakao, H., Mundt, M. & Groner, B. EMBO J. 13, 4361–4369 (1994).

    CAS  Article  Google Scholar 

  19. Liu, X., Robinson, G. W., Gouilleux, F., Groner, B. & Hennighausen, L. Proc. Natl Acad. Sci. USA 92, 8831–8835 (1995).

    ADS  CAS  Article  Google Scholar 

  20. Doppler, W., Groner, B. & Ball, R. K. Proc. Natl Acad. Sci. USA 86, 104–108 (1989).

    ADS  CAS  Article  Google Scholar 

  21. Groner, B., Altiok, S. & Meier, V. Mol. Cell. Endocrinoi. 100, 109–114 (1994).

    CAS  Article  Google Scholar 

  22. Groner, B. & Gouilleux, F. Curr. Op. Gen. Develop. 5, 587–594 (1995).

    CAS  Article  Google Scholar 

  23. Welte, T., Phillipp, S., Cairns, C., Gustafsson, J.-A. & Doppler, W. J. Steroid Biochem. Mol. Biol. 47, 75–81 (1993).

    CAS  Article  Google Scholar 

  24. Hynes, N. E., Kennedy, N., Rahmsdorf, U. & Groner, B. Proc. Natl Acad. Sci. USA 78, 2038–2042 (1981).

    ADS  CAS  Article  Google Scholar 

  25. Hynes, N. E. et al. Proc. Natl Acad. Sci. USA 80, 3637–3641 (1983).

    ADS  CAS  Article  Google Scholar 

  26. Moriggl, R. et al. Mol. Cell. Biol. 16, 5691–5700 (1996).

    CAS  Article  Google Scholar 

  27. LaVoie, H. A. & Witorsch, R. J. Proc. Natl Soc. Exp. Biol. Med. 209, 257–269 (1995).

    CAS  Article  Google Scholar 

  28. Teurich, S. & Angel, P. Chem. Senses 20, 251–255 (1995).

    CAS  Article  Google Scholar 

  29. Cato, A. C. B. & Wade, E. BioEssays 18, 371–378 (1996).

    CAS  Article  Google Scholar 

  30. Ivashkiv, L. B. Immunity 3, 1–4 (1995).

    CAS  Article  Google Scholar 

Download references

Author information

Affiliations

  1. Institute for Experimental Cancer Research, Tumor Biology Center, Breisacher Strasse, 117, D-79106, Freiburg, Germany

    Elisabeth Stöcklin, Manuela Wissler, Fabrice Gouilleux & Bernd Groner

Authors
  1. Elisabeth Stöcklin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Manuela Wissler
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fabrice Gouilleux
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bernd Groner
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Stöcklin, E., Wissler, M., Gouilleux, F. et al. Functional interactions between Stat5 and the glucocorticoid receptor. Nature 383, 726–728 (1996). https://doi.org/10.1038/383726a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/383726a0

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing