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.

  • Letter
  • Published:

Transactivation by NF-IL6/LAP is enhanced by phosphorylation of its activation domain

Nature volume 364, pages 544–547 (1993)Cite this article

Abstract

ONE of the members of the bZIP family of transcriptional activators1–5 is NF-IL6/LAP (IL-6 DBF, C/EBPβ CRP2). NF-IL6/LAP protein is highly expressed in liver nuclei2, where it has been implicated as a master regulator of the acute-phase response1,3,6,7, induced by interleukin-6 (IL-6) and other inflammatory mediators3,8. Also, NF-IL6/LAP is involved in the activation of the IL-6 promoter in response to IL-1 and bacterial lipopolysaccharide1–6. The control of NF-IL6/LAP expression and activity is complex and poorly understood. Under some conditions the NF-IL6/LAP gene is transcriptionally activated by IL-1 and lipopolysaccharide1, whereas in other instances, its binding to cognate DNA sequences is enhanced by cytokines1,3. Additionally, the ability of constitutively expressed NF-IL6/LAP to activate transcription is strongly augmented by IL-6, through an unknown signalling pathway. We now show that stimulation of the protein kinase C pathway increases the phosphorylation of Ser 105 within the activation domain of NF-IL6/LAP, and enhances its transcriptional efficacy.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Akira, S. et al. EMBO J. 9, 1897–1906 (1990).

    Article  CAS  Google Scholar 

  2. Descombes, P., Chojkier, M., Lichtsteiner, S., Falvey, E. & Schibler, U. Genes Dev. 4, 1541–1551 (1990).

    Article  CAS  Google Scholar 

  3. Poli, V., Mancini, F. P. & Cortese, R. Cell 63, 643–653 (1990).

    Article  CAS  Google Scholar 

  4. Cao, Z., Umek, R. M. & McKnight, S. L. Genes Dev. 5, 1538–1552 (1991).

    Article  CAS  Google Scholar 

  5. Williams, S. C., Cantwell, C. A. & Johnson, P. F. Genes Dev. 5, 1553–1567 (1991).

    Article  CAS  Google Scholar 

  6. Isshiki, H., Akira, S. & Tanabe, O. Molec. cell. Biol. 10, 2757–2764 (1990).

    Article  CAS  Google Scholar 

  7. Poli, V. & Cortese, R. Proc. natn. Acad. Sci. U.S.A. 86, 8202–8206 (1989).

    Article  ADS  CAS  Google Scholar 

  8. Darlington, G. J., Wilson, D. R. & Lachman, L. B. J. Cell Biol. 103, 787–793 (1986).

    Article  CAS  Google Scholar 

  9. Mukaida, N., Shiroo, M. & Matsushima, K. J. Immun. 143, 1366–1371 (1989).

    CAS  PubMed  Google Scholar 

  10. Hensel, G., Meichle, A., Pfizenmaier, K. & Krönke, M. Lymphokine Res. 8, 347–351 (1989).

    CAS  PubMed  Google Scholar 

  11. Nishizawa, M., Tsuchiya, M., Watanabe-Fukunaga, R. & Nagata, S. J. biol. Chem. 265, 5897–5902 (1990).

    CAS  PubMed  Google Scholar 

  12. Metcalf, D. & Nicola, N. A. Leukemia Res. 9, 35–50 (1985).

    Article  CAS  Google Scholar 

  13. Seelentag, W. K., Mermod, J.-J., Montesano, R. & Vassali, P. EMBO J. 6, 2261–2265 (1987).

    Article  CAS  Google Scholar 

  14. Evans, E., Courtois, G. M., Killan, P. L., Fuller, G. M. & Crabtree, G. R. J. biol. Chem. 262, 10850–10854 (1987).

    CAS  PubMed  Google Scholar 

  15. Ray, A., Tatter, S. B., May, L. T. & Sehgal, P. B. Proc. natn. Acad. Sci. U.S.A. 85, 6701–6705 (1988).

    Article  ADS  CAS  Google Scholar 

  16. Castagna, M. et al. J. biol. Chem. 257, 7847–7851 (1982).

    CAS  PubMed  Google Scholar 

  17. James, G. & Olson, E. J. Cell Biol. 116, 863–874 (1992).

    Article  CAS  Google Scholar 

  18. Descombes, P. & Schibler, U. Cell 67, 569–579 (1991).

    Article  CAS  Google Scholar 

  19. Boyle, W. J., van der Geer, P. & Hunter, T. Meth. Enym. 201, 110–149 (1991).

    CAS  Google Scholar 

  20. Müller, C. R., Maire, P. & Schibler, U. Cell 61, 279–291 (1990).

    Article  Google Scholar 

  21. Sadowski, I. & Ptashne, M. Nucleic Acids Res. 17, 7639 (1989).

    Article  Google Scholar 

  22. Li, L. et al. Cell 71, 1181–1194 (1992).

    Article  CAS  Google Scholar 

  23. Brenner, D. A., O'Hara, M., Angel, P., Chojkier, M. & Karin, M. Nature 337, 661–663 (1989).

    Article  ADS  CAS  Google Scholar 

  24. Boyle, W. J. et al. Cell 64, 573–584 (1991).

    Article  CAS  Google Scholar 

  25. Binetruy, B., Smeal, T. & Karin, M. Nature 351, 122–127 (1991).

    Article  ADS  CAS  Google Scholar 

  26. Smeal, T., Binetruy, B., Mercola, D., Birrer, M. & Karin, M. Nature 354, 494–496 (1991).

    Article  ADS  CAS  Google Scholar 

  27. Gonzalez, G. & Montminy, M. R. Cell 59, 675–680 (1989).

    Article  CAS  Google Scholar 

  28. Karin, M. & Hunter, T. Cell 70, 375–387 (1992).

    Article  Google Scholar 

  29. Metz, R. & Ziff, E. Genes Dev. 5, 1754–1766 (1991).

    Article  CAS  Google Scholar 

  30. Gauldie, J., Richards, C., Harnish, D., Lansdorp, P. & Bauman, H. Proc. natn. Acad. Sci. U.S.A. 84, 7251–7256 (1987).

    Article  ADS  CAS  Google Scholar 

  31. Dignam J. D., Lebovitz, R. M. & Roeder, R. G. Nucleic Acids Res. 11, 1475–1489 (1983).

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Michael Karin: To whom correspondence should be addressed.

Authors and Affiliations

  1. Department of Medicine,

    Christian Trautwein & Mario Chojkier

  2. Center for Molecular Genetics, University of California at San Diego,

    Christian Trautwein & Mario Chojkier

  3. Veterans Affairs Medical Center, 9500 Oilman Drive, La Jolla, California, 92093-0636, USA

    Christian Trautwein & Mario Chojkier

  4. Department of Pharmacology,

    Christian Trautwein, Carme Caelles & Michael Karin

  5. Center for Molecular Genetics, University of California at San Diego,

    Christian Trautwein, Carme Caelles & Michael Karin

  6. Veterans Affairs Medical Center, 9500 Oilman Drive, La Jolla, California, 92093-0636, USA

    Christian Trautwein, Carme Caelles & Michael Karin

  7. The Salk Institute for Biological Studies, La Jolla, California, 92186, USA

    Peter van der Geer & Tony Hunter

Authors
  1. Christian Trautwein
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carme Caelles
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter van der Geer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tony Hunter
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michael Karin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mario Chojkier
    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

Trautwein, C., Caelles, C., van der Geer, P. et al. Transactivation by NF-IL6/LAP is enhanced by phosphorylation of its activation domain. Nature 364, 544–547 (1993). https://doi.org/10.1038/364544a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/364544a0

This article is cited by

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