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
Treisman, R., Novak, U., Favaloro, J. & Kamen, R. Nature 292, 595–600 (1981).
Courtneidge, S. A. Cancer Surv. 5, 173–182 (1986).
Kaplan, D. R., Pallas, D. C., Morgan, W., Schaffhausen, B. & Roberts, T. M. Biochim. biophys. Acta 948, 345–364 (1989).
Harvey, R., Oostra, B. A., Belsham, G. J., Gillett, P. & Smith, A. E. Molec. cell. Biol. 4, 1334–1342 (1984).
Hunter, T., Hutchinson, M. A. & Eckhart, W. EMBO J. 3, 73–79 (1984).
Talmage, D. A. et al. Cell 59, 55–65 (1989).
Yoakim, M. et al. J. Virol. 66, 5485–5491 (1992).
Auger, K. R., Carpenter, C. L., Shoelson, S. E., Piwnica-Worms, H. & Cantley, L. C. J. biol. Chem. 267, 5408–5415 (1992).
Pelicci, G. et al. Cell 70, 93–104 (1992).
Rozakis-Adcock, M. et al. Nature 360, 689–692 (1992).
McCormick, F. Nature 363, 15–16 (1993).
McGlade, J., Cheng, A., Pelicci, G., Pelicci, P. G. & Pawson, T. Proc. natn. Acad. Sci. U.S.A. 89, 8869–8873 (1992).
Griffin, B. E. et al. Cold Spring Harb. Symp. quant. Biol. 1, 271–283 (1980).
Markland, W. & Smith, A. E. Biochim. biophys. Acta 907, 299–321 (1987).
Druker, B. J., Ling, L. E., Cohen, B., Roberts, T. M. & Schaffhausen, B. S. J. Virol. 64, 4454–4461 (1990).
Dilworth, S. M. & Horner, V. P. J. Virol. 67, 2235–2244 (1993).
Carmichael, G., Schaffhausen, B. S., Mandel, G., Liang, T. J. & Benjamin, T. L. Proc. natn. Acad. Sci. U.S.A. 81, 679–683 (1984).
Markland, W. et al. J. Virol. 59, 384–391 (1986).
Dilworth, S. M. EMBO J. 1, 1319–1328 (1982).
Courtneidge, S. A. & Heber, A. Cell 50, 1031–1037 (1987).
Kaplan, D. R. et al. Cell 50, 1021–1029 (1987).
Raptis, L. et al. J. Virol. 65, 5203–5210 (1991).
Jelinek, M. A. & Hassell, J. A. Oncogene 7, 1687–1698 (1992).
Lowenstein, E. J. et al. Cell 70, 431–442 (1992).
Songyang, Z. et al. Cell 72, 767–778 (1993).
Segatto, O. et al. Oncogene 8, 2105–2112 (1993).
Laemmli, U. K. Nature 227, 680–685 (1970).
Ho, S. N., Hunt, H. D., Horton, R. M., Pullen, J. K. & Pease, L. R. Gene 77, 51–59 (1989).
Smith, D. B. & Johnson, K. S. Gene 67, 31–40 (1988).
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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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DOI: https://doi.org/10.1038/367087a0
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