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:

Role of kinases and the phosphatase calcineurin in the nuclear shuttling of transcription factor NF-AT4

Abstract

A NEW facet of calcium signalling involves the nuclear import of the NF-AT transcription factors from their dormant position in the cytoplasm1–3. The protein phosphatase calcineurin appears to play an essential role in activating NF-AT nuclear import, as the calcineurin inhibitors cyclosporin A and FK506 block dephosphorylation and nuclear import of NF-AT (refs 4–7). Here we show that calcium signalling induces an association between NF-AT4 and calcineurin, and that these molecules are transported, as a complex, to the nucleus, where calcineurin continues to dephosphorylate NF-AT4. We propose that a nuclear complex of NF-AT4 and calcineurin maintains calcium signalling by counteracting a vigorous nuclear NF-AT kinase.

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

Access options

Buy this article

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

Similar content being viewed by others

References

  1. Schreiber, S. L. & Crabtree, G. R. Immun. Today 13, 136–142 (1992).

    Article  CAS  Google Scholar 

  2. Crabtree, G. R. & Clipstone, N. A. A. Rev. Biochem. 63, 1045–1083 (1994).

    Article  CAS  Google Scholar 

  3. Rao, A. Immun. Today 15, 274–281 (1994).

    Article  CAS  Google Scholar 

  4. Flanagan, W. M., Corthesy, B., Bram, R. J. & Crabtree, G. R. Nature 352, 803–807 (1991).

    Article  ADS  CAS  Google Scholar 

  5. Liu, J. et al. Cell 66, 807–815 (1991).

    Article  CAS  Google Scholar 

  6. Ruff, V. A. & Leach, K. L. J. biol. Chem. 270, 22602–22607 (1995).

    Article  CAS  Google Scholar 

  7. Shaw, K. T.-Y. et al. Proc. natn. Acad. Sci. U.S.A. 92, 11205–11209 (1995).

    Article  ADS  CAS  Google Scholar 

  8. Hoey, T., Sun, Y. L., Williamson, K. & Xu, X. Immunity 2, 461–472 (1995).

    Article  CAS  Google Scholar 

  9. Masuda, E. S. et al. Molec. cell. Biol. 15, 2697–2706 (1995).

    Article  CAS  Google Scholar 

  10. Chalfie, M., Tu, Y., Euskirchen, G., Ward, D. D. & Prasher, D. C. Science 263, 802–805 (1994).

    Article  ADS  CAS  Google Scholar 

  11. Wesselborg, S., Fruman, D. A., Sagoo, J. K., Bierer, B. E. & Burakoff, S. J. J. biol. Chem. 271, 1274–1277 (1996).

    Article  CAS  Google Scholar 

  12. Loh, C. et al. J. biol. Chem. 271, 10884–10891 (1996).

    Article  CAS  Google Scholar 

  13. Hubbard, M. J. & Klee, C. B. Biochemistry 28, 1868–1874 (1989).

    Article  CAS  Google Scholar 

  14. O'Keefe, S. J., Tamura, J., Kincaid, R. L., Tocci, M. J. & O'Neill, E. A. Nature 357, 692–694 (1992).

    Article  ADS  CAS  Google Scholar 

  15. Shibasaki, F. & McKeon, F. J. Cell Biol. 131, 735–743 (1995).

    Article  CAS  Google Scholar 

  16. Klee, C. B., Draetta, G. F. & Hubbard, M. J. Adv. Enzym. relat. Areas molec. Biol. 61, 149–200 (1988).

    CAS  Google Scholar 

  17. Goldberg, J. et al. Nature 376, 745–753 (1995).

    Article  ADS  CAS  Google Scholar 

  18. Griffith, J. P. et al. Cell 82, 507–522 (1995).

    Article  CAS  Google Scholar 

  19. Milan, D., Griffith, J., Su, M., Price, E. R. & McKeon, F. Cell 79, 437–447 (1994).

    Article  CAS  Google Scholar 

  20. Karin, M. & Hunter, T. Curr. Biol. 5, 747–757 (1995).

    Article  CAS  Google Scholar 

  21. Chen, R. H., Sarnecki, C. & Blenis, J. Molec. cell Biol. 12, 915–927 (1992).

    Article  CAS  Google Scholar 

  22. Tyers, M. & Futcher, B. Molec. cell. Biol. 13, 5659–5669 (1993).

    Article  CAS  Google Scholar 

  23. Peter, M., Garter, A., Horecka, J., Ammerer, G. & Herskowitz, I. Cell 73, 747–760 (1993).

    Article  CAS  Google Scholar 

  24. Hibi, M., Lin, A., Smeal, T., Minden, A. & Karin, M. Genes Dev. 7, 2135–2148 (1993).

    Article  CAS  Google Scholar 

  25. Heald, R., McLoughlin, M. & McKeon, F. Cell 74, 463–474 (1993).

    Article  CAS  Google Scholar 

  26. Guerini, D. & Klee, C. B. Proc. natn. Acad. Sci. U.S.A. 86, 9183–9187 (1989).

    Article  ADS  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shibasaki, F., Price, E., Milan, D. et al. Role of kinases and the phosphatase calcineurin in the nuclear shuttling of transcription factor NF-AT4. Nature 382, 370–373 (1996). https://doi.org/10.1038/382370a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/382370a0

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

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