Catalytic specificity of protein-tyrosine kinases is critical for selective signalling (original) (raw)

Nature volume 373, pages 536–539 (1995) Cite this article

Abstract

HOW do distinct protein-tyrosine kinases activate specific downstream events? Src-homology-2 (SH2) domains on tyrosine kinases or targets of tyrosine kinases recognize phosphotyrosine in a specific sequence context and thereby provide some specificity1–3. The role of the catalytic site of tyrosine kinases in determining target specificity has not been fully investigated. Here we use a degenerate peptide library to show that each of nine tyrosine kinases investigated has a unique optimal peptide substrate. We find that the cytosolic tyrosine kinases preferentially phosphorylate peptides recognized by their own SH2 domains or closely related SH2 domains (group I; ref. 3), whereas receptor tyrosine kinases preferentially phosphorylate peptides recognized by subsets of group III SH2 domains3. The importance of these findings for human disease is underscored by our observation that a point mutation in the RET receptor-type tyrosine kinase, which causes multiple endocrine neoplasia type 2B, results in a shift in peptide substrate specificity.

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

Access options

Subscribe to this journal

Receive 52 print issues and online access

$199.00 per year

only $3.83 per issue

Buy this article

USD 39.95

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

Additional access options:

Similar content being viewed by others

References

  1. Cantley, L. C. et al. Cell 64, 281–302 (1991).
    Article CAS Google Scholar
  2. Pawson, T. & Schlessinger, J. Curr. Biol. 3, 434–442 (1993).
    Article CAS Google Scholar
  3. Songyang, Z. et al. Cell 72, 767–778 (1993).
    Article CAS Google Scholar
  4. Songyang, Z. et al. Curr. Biol. 4, 973–982 (1994).
    Article CAS Google Scholar
  5. Patschinsky, T., Hunter, T., Esch, F. S., Cooper, J. A. & Sefton, B. M. Proc. natn. Acad. Sci. U.S.A. 79, 973–977 (1982).
    Article ADS CAS Google Scholar
  6. Hunter, T. J. biol. Chem. 257, 4843–4848 (1982).
    CAS PubMed Google Scholar
  7. Cooper, J. A., Esch, F. S., Taylor, S. S. & Hunter, T. J. biol. Chem. 259, 7835–7841 (1984).
    CAS PubMed Google Scholar
  8. Tinker, D. A., Cartron, J. L., McMurray, J. S. & Levin, V. A. Anticancer Res. 12, 123–128 (1992).
    CAS PubMed Google Scholar
  9. Till, J. H., Annan, R. S., Cart, S. A. & Miller, W. T. J. biol. Chem. 269, 7423–7428 (1994).
    CAS PubMed Google Scholar
  10. Pearson, R. B. & Kemp, B. E. Meth. Enzym. 200, 63–81 (1991).
    Google Scholar
  11. Valius, M. & Kazlauskas, A. Cell 73, 321–334 (1993).
    Article CAS Google Scholar
  12. Reth, M. Nature 338, 383–384 (1989).
    Article ADS CAS Google Scholar
  13. Sakai, R. et al. EMBO J. 13, 3748–3756 (1994).
    Article CAS Google Scholar
  14. Songyang, Z. et al. Molec. cell. Biol. 14, 2777–2785 (1994).
    Article CAS Google Scholar
  15. Areces, L. B., Sbarba, P. D., Jucker, M., Stanley, E. R. & Feldman, R. A. Molec. cell. Biol. 14, 4606–4615 (1994).
    Article CAS Google Scholar
  16. Hofstra, R. M. et al. Nature 367, 375–376 (1994).
    Article ADS CAS Google Scholar
  17. Eng, C. et al. Hum. molec. Genet. 3, 237–241 (1994).
    Article CAS Google Scholar
  18. Carlson, K. M. et al. Proc. natn. Acad. Sci. U.S.A. 91, 1579–1583 (1994).
    Article ADS CAS Google Scholar
  19. Hanks, S. K., Quinn, A. M. & Hunter, T. Science 241, 42–52 (1988).
    Article ADS CAS Google Scholar
  20. Knighton, D. R. et al. Science 253, 414–420 (1991).
    Article ADS CAS Google Scholar
  21. Duyster, J., Baskaran, R. & Wang, J. Y. J. Proc. natn. Acad. Sci. U.S.A. (in the press).
  22. Piwnica-Worms, H., Williams, N. G., Cheng, S. H. & Roberts, T. M. J. Virol. 64, 61–68 (1990).
    CAS PubMed PubMed Central Google Scholar
  23. Carraway III, K. L. & Cerione, R. A. J. biol. Chem. 268, 23860–23867 (1993).
    CAS PubMed Google Scholar
  24. Mayer, B. J. & Baltimore, D. Molec. cell. Biol. 14, 2883–2894 (1994).
    Article CAS Google Scholar
  25. Shoelson, S. E., Chatterjee, S., Chaudhuri, M. & White, M. F. Proc. natn. Acad. Sci. U.S.A. 89, 2027–2031 (1992).
    Article ADS CAS Google Scholar

Download references

Author information

Authors and Affiliations

  1. Division of Signal Transduction, Department of Medicine, Beth Israel Hospital and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, 02215, USA
    Zhou Songyang, Kermit L. Carraway III & Lewis C. Cantley
  2. Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts, 02111, USA
    Zhou Songyang & Stephen C. Harrison
  3. Howard Hughes Medical Institute and Laboratory of Molecular Medicine, Children's Hospital, Boston, Massachusetts, 02115, USA
    Michael J. Eck & Bruce J. Mayer
  4. Department of Microbiology and Immunology, University of Maryland School of Medicine, and Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, Maryland, 21201, USA
    Ricardo A. Feldman
  5. Department of Pharmacology, New York University Medical Center, New York, New York, 10016, USA
    Moosa Mohammadi & Joseph Schlessinger
  6. Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York, 10032, USA
    Stevan R. Hubbard
  7. CRC Human Cancer Genetics Research Group, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK
    Darrin P. Smith, Charis Eng, Marla J. Lorenzo & Bruce A. J. Ponder
  8. Department of Medicine, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, 02115, USA
    Charis Eng
  9. Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts, 02115, USA
    Bruce J. Mayer

Authors

  1. Zhou Songyang
  2. Kermit L. Carraway III
  3. Michael J. Eck
  4. Stephen C. Harrison
  5. Ricardo A. Feldman
  6. Moosa Mohammadi
  7. Joseph Schlessinger
  8. Stevan R. Hubbard
  9. Darrin P. Smith
  10. Charis Eng
  11. Marla J. Lorenzo
  12. Bruce A. J. Ponder
  13. Bruce J. Mayer
  14. Lewis C. Cantley

Rights and permissions

About this article

Cite this article

Songyang, Z., Carraway , K., Eck, M. et al. Catalytic specificity of protein-tyrosine kinases is critical for selective signalling.Nature 373, 536–539 (1995). https://doi.org/10.1038/373536a0

Download citation