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.

Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction

Abstract

A serine/threonine kinase, named protein kinase B (PKB)1 for its sequence homology to both protein kinase A and C, has previously been isolated. PKB, which is identical to the kinase Rac2, was later found to be the cellular homologue of the transforming v-Akt3. Here we show that PKB is activated by stimuli such as insulin, platelet-derived growth factor (PDGF), epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). Activation of PKB was inhibited by the phosphatidylinositol-3-OH kinase (PI(3)K) inhibitor wortmannin and by coexpression of a dominant-negative mutant of PI(3)K. PDGF receptor mutants that lack detectable associated PI(3)K activity also fail to induce PKB activation. PKB kinase activity is correlated with phosphorylation of PKB on serine. Finally, we show that a constructed Gag–PKB fusion protein, homologous to the v-akt oncogene, displays significantly increased ligand-independent kinase activity. Furthermore, this activity is sufficient to activate the p70 S6-kinase (p70S6k). These results suggest a role for PKB in PI(3)K-mediated signal transduction.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

References

  1. Coffer, P. J. & Woodgett, J. R. Eur. J. Biochem. 201, 475–481 (1991).

    Article  CAS  PubMed  Google Scholar 

  2. Jones, P. F., Jakubowicz, T., Pitossi, F. J., Maurer, F. & Hemmings, B. A. Proc. natn. Acad. Sci. U.S.A. 88, 4171–4175 (1991).

    Article  ADS  CAS  Google Scholar 

  3. Belacossa, A., Testa, J. R., Staal, S. P. & Tschilis, P. N. Science 254, 274–277 (1991).

    Article  ADS  Google Scholar 

  4. Burgering, B. M. T. et al. Molec. cell. Biol. 13, 7248–7256 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. de Vries-Smits, A. M. M., Burgering, B. M. T., Leevers, S. J., Marshall, C. J. & Bos, J. L. Nature 357, 602–604 (1992).

    Article  ADS  CAS  PubMed  Google Scholar 

  6. Ming, X.-F. et al. Nature 371, 426–429 (1994).

    Article  ADS  CAS  PubMed  Google Scholar 

  7. Arcaro, A. & Wymann, M. P. Biochem. J. 296, 297–301 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Fantl, W. J. et al. Cell 69, 413–423 (1992).

    Article  CAS  PubMed  Google Scholar 

  9. Burgering, B. M. T., Freed, E., McCormick, F. & Bos, J. L. Cell, Growth Diff. 5, 341–347 (1993).

    Google Scholar 

  10. Wennström, S. et al. Oncogene 9, 651–660 (1994).

    PubMed  Google Scholar 

  11. Hara, K. et al. Proc. natn. Acad. Sci. U.S.A. 91, 7415–7419 (1994).

    Article  ADS  CAS  Google Scholar 

  12. Chung, J., Grammer, T. C., Lemon, K. P., Kazlauskas, A. & Blenis, J. Nature 370, 71–75 (1994).

    Article  ADS  CAS  PubMed  Google Scholar 

  13. Franke, T. F. et al. Cell 81, 727–736 (1995).

    Article  CAS  PubMed  Google Scholar 

  14. Hu, Q., Klippel, A., Muslin, A. J., Fautl, W. J. & Williams, L. T. Science 268, 100–102 (1995).

    Article  ADS  CAS  PubMed  Google Scholar 

  15. Rodriguez-Viciana, P. et al. Nature 370, 527–532 (1994).

    Article  ADS  CAS  PubMed  Google Scholar 

  16. Qiu, R.-G., Chen, J., Kirn, D., McCormick, F. & Symons, M. Nature 374, 457–459 (1995).

    Article  ADS  CAS  PubMed  Google Scholar 

  17. Green, S., Isseman, I. & Sheer, E. Nucleic Acids Res. 16, 369 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Field, J. et al. Molec. cell. Biol. 8, 2159–2165 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Burgering, B., Coffer, P. Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction. Nature 376, 599–602 (1995). https://doi.org/10.1038/376599a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/376599a0

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