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Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling

Nature volume 363, pages 85–88 (1993)Cite this article

Abstract

MANY of the actions of receptor tyrosine kinases are mediated by the protein Ras1–5, including the activation of various downstream serine/threonine kinases and the stimulation of growth and differentiation6–12. The human protein Grb2 binds to ligand-activated growth factor receptors and downstream effector proteins through its Src-homology (SH) domains SH2 and SH3, respectively13,14, and like its homologue from Caenorhabditis elegans, Sem-5, apparently forms part of a highly conserved pathway by which these receptors can control Ras activity15–18. Here we show that the SH3 domains of Grb2 bind to the carboxy-terminal part of hSos1, the human homologue of the Drosophila guanine-nucleotide-releasing factor for Ras, which is essential for control of Ras activity by epidermal growth factor receptor and sevenless19,20. Moreover, a synthetic 10-amino-acid peptide containing the sequence PPVPPR specifically blocks the interaction. These results indicate that the Grbl/hSos1 complex couples activated EGF receptor to Ras signalling.

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References

  1. Ullrich, A. & Schlessinger, J. Cell 61, 203–212 (1990).

    Article  CAS  Google Scholar 

  2. Satoh, T. et al. Proc. natn. Acad. Scl. U.S.A. 87, 7926–7929 (1990).

    Article  ADS  CAS  Google Scholar 

  3. Satoh, T., Endo, M., Nakafuku, M., Nakamura, S. & Kaziro, Y. Proc. natn. Acad. Scl. U.S.A. 87, 5993–5997 (1990).

    Article  ADS  CAS  Google Scholar 

  4. Zhang, K., Papageorge, A. G. & Lowy, D. R. Science 257, 671–674 (1992).

    Article  ADS  CAS  Google Scholar 

  5. Medema, R. H., de Vries-Smits, A. M. M., van der Zon, G. C. M., Maassen, J. A. & Bos, J. L. Molec. cell. Biol. 13, 155–162 (1993).

    Article  CAS  Google Scholar 

  6. Mulcahy, L. S., Smith, M. R. & Stacey, D. W. Nature 313, 241–248 (1985).

    Article  ADS  CAS  Google Scholar 

  7. Smith, M. R., DeGudicibus, S. J. & Stacey, D. W. Nature 320, 540–543 (1986).

    Article  ADS  CAS  Google Scholar 

  8. Hagag, N., Halegoua, S. & Viola, M. Nature 319, 680–682 (1986).

    Article  ADS  CAS  Google Scholar 

  9. Thomas, S. M., DeMarco, M., D'Arcangelo, G., Halegoua, S. & Brugge, J. S. Cell 68, 1031–1040 (1992).

    Article  CAS  Google Scholar 

  10. Wood, K. W., Sarnecki, C., Roberts, T. M. & Blennis, J. Cell 68, 1041–1050 (1992).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  12. Szeberenyi, J., Cai, H. & Cooper, G. M. Molec. cell. Biol. 10, 5324–5332 (1990).

    Article  CAS  Google Scholar 

  13. Lowenstein, E. J. et al. Cell 70, 431–442 (1992).

    Article  CAS  Google Scholar 

  14. Skolnik, E. et al. EMBO J. (in the press).

  15. Clark, S. G., Stern, M. J. & Horvitz, H. R. Nature 356, 340–344 (1992).

    Article  ADS  CAS  Google Scholar 

  16. Aroian, R. V., Koga, M., Mendel, J. E., Ohshima, Y. & Sternberg, P. W. Nature 348, 693–699 (1990).

    Article  ADS  CAS  Google Scholar 

  17. Beitel, G. J., Clark, S. G. & Horovitz, H. R. Nature 348, 503–509 (1990).

    Article  ADS  CAS  Google Scholar 

  18. Bowtell, D., Fu, O., Simon, M. & Senior, P. Proa natn. Acad. Sci. U.S.A. 89, 6511–6515 (1992).

    Article  ADS  CAS  Google Scholar 

  19. Simon, M. A., Bowtell, S. D. L., Dodson, G. S., Laverty, T. R. & Rubin, G. M. Cell 67, 701–716 (1991).

    Article  CAS  Google Scholar 

  20. Rogge, R. R., Karlovich, C. A. & Banerjee, V. Cell 64, 39–48 (1991).

    Article  CAS  Google Scholar 

  21. Rozakis-Adcock, M., Fernley, R., Wade, J., Pawson, A. & Bowtell, D. Nature 362, XXX–XXX (1993).

    Google Scholar 

  22. Rozakis-Adcock, M. et al. Nature 360, 689–692 (1992).

    Article  ADS  CAS  Google Scholar 

  23. Cicchetti, P., Mayer, B. J., Thiel, G. & Baltimore, D. Science 257, 803–806 (1992).

    Article  ADS  CAS  Google Scholar 

  24. Felder, S. et al. Molec. cell. Biol. 13, 1449–1455 (1993).

    Article  CAS  Google Scholar 

  25. Gale, N. W., Kaplan, S., Lowenstein, E. J., Schlessinger, J. & Bar-Sagi, D. Nature (submitted).

  26. Olivier, J. P. et al. Cell 73, 179–191 (1993).

    Article  CAS  Google Scholar 

  27. Simon, M. A., Dodson, G. S. amp; Rubin, G. M. Cell 73, 169–177 (1993).

    Article  CAS  Google Scholar 

  28. Gross, E., Goldberg, D. & Levitzki, A. Nature 360, 762–765 (1992).

    Article  ADS  CAS  Google Scholar 

  29. Margolis, B. et al. Nature 356, 71–74 (1992).

    Article  ADS  CAS  Google Scholar 

  30. Margolis, B. et al. EMBO J. 90, 4375–4380 (1990).

    Article  Google Scholar 

Download references

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Authors and Affiliations

  1. New York University Medical Center, Department of Pharmacology and Kaplan Cancer Center, 550 First Avenue, New York, New York, 10016, USA

    N. Li, A. Batzer, R. Daly, V. Yajnik, E. Skolnik, B. Margolis & J. Schlessinger

  2. Institute de Pharmacologie Moleculaire et Cellulaire du CNRS, 660 Route de Lucioles, 06560, Volbonne, France

    P. Chardin

  3. Cold Spring Harbor Laboratories, PO Box 100, One Bungtown Road, Cold Spring Harbor, New York, 11724, USA

    D. Bar-Sagi

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  1. N. Li
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Li, N., Batzer, A., Daly, R. et al. Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling. Nature 363, 85–88 (1993). https://doi.org/10.1038/363085a0

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