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Transformation by polyoma virus middle T-antigen involves the binding and tyrosine phosphorylation of Shc

Nature volume 367, pages 87–90 (1994)Cite this article

Abstract

POLYOMA virus middle T-antigen converts normal fibroblasts to a fully transformed, tumorigenic phenotype1. It achieves this, at least in part, by binding and activating one of the non-receptor tyrosine kinases, pp60c-src, pp62c-yes or pp59c-fyn (reviewed in refs 2 and 3). As a result, middle T-antigen itself is phosphorylated on tyrosine residues4,5, one of which (Tyr 315) acts as a binding site for the SH2 domains of phosphatidylinositol-3'OH kinase 85K sub-unit6–8. Here we show that another tyrosine phosphorylation site in middle T-antigen (Tyr 250; refs 4, 5) acts as a binding region for the SH2 domain of the transforming protein Shc9. This results in Shc also becoming tyrosine-phosphorylated and binding to the SH2 domain of Grb2 (ref. 10). This probably stimulates p21ras activity through the mammalian homologue of the Drosophila guanine-nucleotide-exchange factor Sos (reviewed in ref. 11). We suggest that middle T-antigen transforms cells by acting as a functional homologue of an activated tyrosine kinase-associated growth-factor receptor.

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References

  1. Treisman, R., Novak, U., Favaloro, J. & Kamen, R. Nature 292, 595–600 (1981).

    Article  ADS  CAS  Google Scholar 

  2. Courtneidge, S. A. Cancer Surv. 5, 173–182 (1986).

    CAS  PubMed  Google Scholar 

  3. Kaplan, D. R., Pallas, D. C., Morgan, W., Schaffhausen, B. & Roberts, T. M. Biochim. biophys. Acta 948, 345–364 (1989).

    CAS  PubMed  Google Scholar 

  4. Harvey, R., Oostra, B. A., Belsham, G. J., Gillett, P. & Smith, A. E. Molec. cell. Biol. 4, 1334–1342 (1984).

    Article  CAS  Google Scholar 

  5. Hunter, T., Hutchinson, M. A. & Eckhart, W. EMBO J. 3, 73–79 (1984).

    Article  CAS  Google Scholar 

  6. Talmage, D. A. et al. Cell 59, 55–65 (1989).

    Article  CAS  Google Scholar 

  7. Yoakim, M. et al. J. Virol. 66, 5485–5491 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Auger, K. R., Carpenter, C. L., Shoelson, S. E., Piwnica-Worms, H. & Cantley, L. C. J. biol. Chem. 267, 5408–5415 (1992).

    CAS  PubMed  Google Scholar 

  9. Pelicci, G. et al. Cell 70, 93–104 (1992).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  11. McCormick, F. Nature 363, 15–16 (1993).

    Article  ADS  CAS  Google Scholar 

  12. McGlade, J., Cheng, A., Pelicci, G., Pelicci, P. G. & Pawson, T. Proc. natn. Acad. Sci. U.S.A. 89, 8869–8873 (1992).

    Article  ADS  CAS  Google Scholar 

  13. Griffin, B. E. et al. Cold Spring Harb. Symp. quant. Biol. 1, 271–283 (1980).

    Article  Google Scholar 

  14. Markland, W. & Smith, A. E. Biochim. biophys. Acta 907, 299–321 (1987).

    CAS  PubMed  Google Scholar 

  15. Druker, B. J., Ling, L. E., Cohen, B., Roberts, T. M. & Schaffhausen, B. S. J. Virol. 64, 4454–4461 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Dilworth, S. M. & Horner, V. P. J. Virol. 67, 2235–2244 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Carmichael, G., Schaffhausen, B. S., Mandel, G., Liang, T. J. & Benjamin, T. L. Proc. natn. Acad. Sci. U.S.A. 81, 679–683 (1984).

    Article  ADS  CAS  Google Scholar 

  18. Markland, W. et al. J. Virol. 59, 384–391 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Dilworth, S. M. EMBO J. 1, 1319–1328 (1982).

    Article  CAS  Google Scholar 

  20. Courtneidge, S. A. & Heber, A. Cell 50, 1031–1037 (1987).

    Article  CAS  Google Scholar 

  21. Kaplan, D. R. et al. Cell 50, 1021–1029 (1987).

    Article  CAS  Google Scholar 

  22. Raptis, L. et al. J. Virol. 65, 5203–5210 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Jelinek, M. A. & Hassell, J. A. Oncogene 7, 1687–1698 (1992).

    CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  25. Songyang, Z. et al. Cell 72, 767–778 (1993).

    Article  CAS  Google Scholar 

  26. Segatto, O. et al. Oncogene 8, 2105–2112 (1993).

    CAS  PubMed  Google Scholar 

  27. Laemmli, U. K. Nature 227, 680–685 (1970).

    Article  ADS  CAS  Google Scholar 

  28. Ho, S. N., Hunt, H. D., Horton, R. M., Pullen, J. K. & Pease, L. R. Gene 77, 51–59 (1989).

    Article  CAS  Google Scholar 

  29. Smith, D. B. & Johnson, K. S. Gene 67, 31–40 (1988).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Chemical Pathology, Royal Postgraduate Medical School, Du Cane Road, London, W12 ONN, UK

    Stephen M. Dilworth & Charlotte E. P. Brewster

  2. Department of Virology, Royal Postgraduate Medical School, Du Cane Road, London, W12 ONN, UK

    Michael D. Jones

  3. Istituto di Clinica Medica I, University of Perugia, Via Brunamonti, 06100, Perugia, Italy

    Luisa Lanfrancone, Guiliana Pelicci & Pier G. Pelicci

Authors
  1. Stephen M. Dilworth
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  2. Charlotte E. P. Brewster
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  4. Luisa Lanfrancone
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  5. Guiliana Pelicci
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  6. Pier G. Pelicci
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Dilworth, S., Brewster, C., Jones, M. et al. Transformation by polyoma virus middle T-antigen involves the binding and tyrosine phosphorylation of Shc. Nature 367, 87–90 (1994). https://doi.org/10.1038/367087a0

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