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:

Phosphorylation inhibits guanine nucleotide exchange on eukaryotic initiation factor 2

Nature volume 296, pages 93–95 (1982)Cite this article

Abstract

There is extensive evidence that protein synthesis in reticulocyte lysates is inhibited during haem deficiency because of phosphorylation of initiation factor eIF-2 by a protein kinase (the haem-controlled represser, HCR)1–5. Other protein kinases, which are activated by low concentrations of double-stranded RNA, have also been identified in reticulocytes1,6 and in extracts from interferon-treated cells7–10, and these phosphorylate an identical site on eIF-2 11–12. Despite the extensive documentation of such enzymes, however, the precise mechanism of inhibition has remained unclear, mainly because phosphorylation fails to affect many partial reactions of polypeptide chain initiation13,14. We present here evidence that the exchange of GTP for GDP bound to eIF-2 is inhibited following phosphorylation of the factor. Such an effect may inactivate eIF-2 by impairing the ability to recycle between successive rounds of protein synthesis.

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. Farrell, P. J., Balkow, K., Hunt, T., Jackson, R. J. & Trachsel, H. Cell 11, 187–200 (1977).

    Article  CAS  Google Scholar 

  2. Safer, B. & Anderson, W. F. CRC crit. Rev. Biochem. 5, 261–290 (1978).

    Article  CAS  Google Scholar 

  3. Clemens, M. J. in The Biochemistry of Cellular Regulation Vol. 1 (ed. Clemens, M. J.) 159–191 (CRC Press, Boca Raton, 1980).

    Google Scholar 

  4. Levin, D. et al. in Protein Phosphorylation and Bio-Regulation (eds Thomas, G., Podesta, E. J. & Gordon, J.) 128–141 (Karger, Basle, 1980).

    Google Scholar 

  5. Austin, S. A. & Clemens, M. J. FEBS Lett. 110, 1–7 (1980).

    Article  CAS  Google Scholar 

  6. Levin, D. H. & London, I. M. Proc. natn. Acad. Sci. U.S.A. 75, 1121–1125 (1978).

    Article  ADS  CAS  Google Scholar 

  7. Roberts, W. K., Hovanessian, A., Brown, R. E., Clemens, M. J. & Kerr, I. M. Nature. 264, 477–480 (1976).

    Article  ADS  CAS  Google Scholar 

  8. Lebleu, B., Sen, G. C., Shaila, S., Cabrer, B. & Lengyel, P. Proc. natn. Acad. Sci. U.S.A. 73, 3107–3111 (1976).

    Article  ADS  CAS  Google Scholar 

  9. Sen, G. C., Taira, H. & Lengyel, P. J. biol. Chem. 253, 5915–5921 (1978).

    CAS  Google Scholar 

  10. West, D. K. & Baglioni, C. Eur. J. Biochem. 101, 461–468 (1979).

    Article  CAS  Google Scholar 

  11. Samuel, C. E. Proc. natn. Acad. Sci. U.S.A. 76, 600–604 (1979).

    Article  ADS  CAS  Google Scholar 

  12. Levin, D. H., Petryshyn, R. & London, I. M. Proc. natn. Acad. Sci. U.S.A. 77, 832–836 (1980).

    Article  ADS  CAS  Google Scholar 

  13. Trachsel, H. & Staehelin, T. Proc. natn. Acad. Sci. U.S.A. 75, 204–208 (1978).

    Article  ADS  CAS  Google Scholar 

  14. Safer, B., Peterson, D. & Merrick, W. C. in Translation of Natural and Synthetic Poly-nucleotides (ed. Legocki, A. B.) 24–31 (Poznan Agricultural University Press, 1977).

    Google Scholar 

  15. Cherbas, L. & London, I. M. Proc. natn. Acad. Sci. U.S.A. 73, 3506–3510 (1976).

    Article  ADS  CAS  Google Scholar 

  16. Pain, V. M. & Clemens, M. J. in Comprehen. Biochem. B19, 1–76 (1980).

    Google Scholar 

  17. Clemens, M. J., Echetebu, C. O., Tilleray, V. J. & Pain, V. M. Biochem. biophys. Res. Commun. 92, 60–67 (1980).

    Article  CAS  Google Scholar 

  18. Barrieux, A. & Rosenfeld, M. G. J. biol. Chem. 252, 3843–3847 (1977).

    CAS  PubMed  Google Scholar 

  19. Peterson, D. T., Safer, B. & Merrick, W. C. J. biol. Chem. 254, 7730–7735 (1979).

    CAS  PubMed  Google Scholar 

  20. Walton, G. M. & Gill, G. N. Biochim. biophys. Acta 390, 231–245 (1975).

    Article  CAS  Google Scholar 

  21. Walton, G. M. & Gill, G. N. Biochim. biophys. Acta 418, 195–203 (1976).

    Article  CAS  Google Scholar 

  22. Benne, R., Amesz, H., Hershey, J. W. B. & Voorma, H. O. J. biol. Chem. 254, 3201–3205 (1979).

    CAS  PubMed  Google Scholar 

  23. Kaziro, Y. Biochim. biophys. Acta 505, 95–127 (1978).

    Article  CAS  Google Scholar 

  24. Grasmuk, H., Nolan, R. D. & Drews, J. Eur. J. Biochem. 92, 479–490 (1978).

    Article  CAS  Google Scholar 

  25. Slobin, L. I. Eur. J. biochem. 96, 287–293 (1979).

    Article  CAS  Google Scholar 

  26. de Haro, C. & Ochoa, S. Proc. natn. Acad. Sci. U.S.A. 75, 2713–2716 (1978).

    Article  ADS  CAS  Google Scholar 

  27. Amesz, H., Goumans, H., Haubrich-Morree, T., Voorma, H. O. & Benne, R. Eur. J. Biochem. 98, 513–520 (1979).

    Article  CAS  Google Scholar 

  28. Ranu, R. S. & London, I. M. Proc. natn. Acad. Sci. U.S.A. 76, 1079–1083 (1979).

    Article  ADS  CAS  Google Scholar 

  29. Das, A. et al. Proc. natn. Acad. Sci. U.S.A. 76, 5076–5079 (1979).

    Article  ADS  CAS  Google Scholar 

  30. Siekierka, J., Mitsui, K-I. & Ochoa, S. Proc. natn. Acad. Sci. U.S.A. 78, 220–223 (1981).

    Article  ADS  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, St George's Hospital Medical School, London, SW17 0RE, UK

    Michael J. Clemens

  2. School of Biological Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, UK

    Virginia M. Pain

  3. Cancer Center, University of Rochester Medical Center, Rochester, New York, 14642, USA

    Sie-Ting Wong & Edgar C. Henshaw

Authors
  1. Michael J. Clemens
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Virginia M. Pain
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sie-Ting Wong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Edgar C. Henshaw
    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

Clemens, M., Pain, V., Wong, ST. et al. Phosphorylation inhibits guanine nucleotide exchange on eukaryotic initiation factor 2. Nature 296, 93–95 (1982). https://doi.org/10.1038/296093a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/296093a0

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