Requirement for integration of signals from two distinct phosphorylation pathways for activation of MAP kinase (original) (raw)

Nature volume 343, pages 651–653 (1990)Cite this article

Abstract

MAP kinase (relative molecular mass, 42,000), a low abundance serine-threonine protein kinase, is transiently activated in many cell types by a variety of mitogens, including insulin, epidermal growth factor, and phorbol esters1,2. In vitro, MAP kinase will phosphorylate and reactivate S6 kinase II previously inactivated by phosphatase treatment3. Because many of the stimuli that activate MAP kinase are also stimulators of cell proliferation, and regulation of the cell cycle seems to involve a network of protein kinases, MAP kinase could be important in the transmission of stimuli eventually leading to the progression from GO to Gl in the cell cycle. Activated MAP kinase contains both phosphotyrosine and phosphothreonine4. We report here that MAP kinase can be deactivated completely by treatment with either phosphatase 2A, a protein phosphatase specific for phosphoserine and phosphothreonine, or CD45, a phosphotyrosine-specific protein phosphatase. We demonstrate that MAP kinase is only active when both tyrosyl and threonyl residues are phosphorylated and suggest therefore that the enzyme functions in vivo to integrate signals from two distinct transduction pathways.

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

Access options

Subscribe to this journal

Receive 51 print issues and online access

$199.00 per year

only $3.90 per issue

Buy this article

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

Additional access options:

Similar content being viewed by others

References

  1. Ray, L. B. & Sturgill, T. W. J. biol. Chem. 263, 12721–12727 (1988).
    CAS PubMed Google Scholar
  2. Rossomando, A. J., Payne, D. M., Weber, M. J. & Sturgill, T. W. Proc. natn. Acad. Sci. U.S.A. 86, 6940–6943 (1989).
    Article ADS CAS Google Scholar
  3. Sturgill, T. W., Ray, L. B., Erikson, E. & Maller, J. L. Nature 334, 715–718 (1988).
    Article ADS CAS Google Scholar
  4. Ray, L. B. & Sturgill, T. W. Proc. natn. Acad. Sci. U.S.A. 85, 3753–3757 (1988).
    Article ADS CAS Google Scholar
  5. Ray, L. B. & Sturgill, T. W. Proc. natn. Acad. Sci. U.S.A. 84, 1502–1506 (1987).
    Article ADS CAS Google Scholar
  6. Cohen, P. A. Rev. Biochem. 58, 453–508 (1989).
    Article CAS Google Scholar
  7. Jones, S. W., Erikson, R. L., Ingebritsen, V. M. & Ingebritsen, T. S. J. biol. Chem. 264, 7747–7753 (1989).
    CAS PubMed Google Scholar
  8. Tonks, N. K., Charbonneau, H., Diltz, C. D., Fischer, E. H. & Walsh, K. A. Biochemistry 27, 8695–8710 (1988).
    Article CAS Google Scholar
  9. Charbonneau, H., Tonks, N. K., Walsh, K. A. & Fischer, E. H. Proc. natn. Acad. Sci. U.S.A. 85, 7182–7186 (1988).
    Article ADS CAS Google Scholar
  10. Cicirelli, M. F., Pelech, S. L. & Krebs, E. G. J. biol. Chem. 263, 2009–2019 (1988).
    CAS PubMed Google Scholar
  11. Kamps, M. P. & Sefton, B. M. Analyt. Biochem. 176, 22–27 (1989).
    Article CAS Google Scholar
  12. Murray, A. W. & Kirschner, M. W. Science 246, 614–621 (1989).
    Article ADS CAS Google Scholar
  13. Morla, A. O., Draetta, G., Beach, D. & Wang, J. Y. J. Cell 58, 193–203 (1989).
    Article CAS Google Scholar
  14. Gregory, J. S., Boulton, T. G., Sang, B. & Cobb, M. H. J. biol. Chem. 264, 18397–18401 (1989).
    CAS PubMed Google Scholar

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine and Pharmacology, University of Virginia School of Medicine, Charlottesville, Virginia, 22908, USA
    Neil G. Anderson & Thomas W. Sturgill
  2. Department of Pharmacology, University of Colorado School of Medicine, Denver, Colorado, 80262, USA
    James L. Maller
  3. Department of Biochemistry, University of Washington, Seattle, Washington, 98195, USA
    Nicholas K. Tonks

Authors

  1. Neil G. Anderson
    You can also search for this author inPubMed Google Scholar
  2. James L. Maller
    You can also search for this author inPubMed Google Scholar
  3. Nicholas K. Tonks
    You can also search for this author inPubMed Google Scholar
  4. Thomas W. Sturgill
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Anderson, N., Maller, J., Tonks, N. et al. Requirement for integration of signals from two distinct phosphorylation pathways for activation of MAP kinase.Nature 343, 651–653 (1990). https://doi.org/10.1038/343651a0

Download citation