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Association of phosphatidylinositol kinase activity with polyoma middle-T competent for transformation

Nature volume 315, pages 239–242 (1985)Cite this article

Abstract

Polyoma middle-T antigen is required for viral transformation of cultured cells and for tumorigenesis in animals. Like many other transforming gene products, middle-T is bound to the membrane and has an associated tyrosine kinase activity in vitro1,2. This activity seems to result from the interaction of middle-T with pp60c-src, the cellular homologue of the transforming gene product of the Rous sarcoma virus, pp60v-src (refs 3–5). Both pp60v-src (ref. 6) and another retrovirus transforming gene product, pp68v-ros (ref. 7) were shown recently to have an associated phosphatidylinositol (PI) kinase activity in vitro and to increase PI turnover in vivo. These results suggest that viral transformation may be directly connected to a complex network of second messengers generated from PI turnover8–18. Here, we assayed for PI kinase activity in immunoprecipitates made with middle-T- or pp60c-src-specific antisera of cells infected with polyoma virus. A PI kinase activity was detected in those immunoprecipitates which contained middle-T. Studies of mutants of middle-T defective in transformation indicate a close correlation between PI kinase activity and transformation.

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References

  1. Smith, A. E. & Ely, B. K. Adv. viral Oncol. 3, 3–87 (1983).

    CAS  Google Scholar 

  2. Schaffhausen, B. S. CRC Rev. Biochem. 13, 215–269 (1983).

    Article  Google Scholar 

  3. Courtneidge, S. & Smith, A. E. Nature 303, 435–439 (1983).

    Article  ADS  CAS  Google Scholar 

  4. Courtneidge, S., Oostra, B. K. & Smith, A. E. Cancer Cells Vol. 2, 123–132 (Cold Spring Harbor Laboratory, New York, 1984).

    Google Scholar 

  5. Sefton, B., Hunter, T., Beemon, K. & Eckhart, W. Cell 20, 807–816 (1980).

    Article  CAS  Google Scholar 

  6. Sugimoto, Y., Whitman, M., Cantley, L. & Erikson, R. Proc. natn. Acad. Sci. U.S.A. 81, 2117–2121 (1984).

    Article  ADS  CAS  Google Scholar 

  7. Macara, I. G., Marinetti, G. V. & Balduzzi, P. C. Proc. natn. Acad. Sci. U.S.A. 81, 2728–2732 (1984).

    Article  ADS  CAS  Google Scholar 

  8. Berridge, M. Biochem. J. 220, 345–360 (1984).

    Article  CAS  Google Scholar 

  9. Michell, R. Phil. Trans. R. Soc. B296, 123–137 (1981).

    Article  CAS  Google Scholar 

  10. Penniston, J. T. Ann. N. Y. Acad. Sci. 402, 296–300 (1982).

    Article  ADS  CAS  Google Scholar 

  11. Carafoli, E. & Zurini, M. Biochim. biophys. Acta 683, 279–301 (1982).

    Article  CAS  Google Scholar 

  12. Smith, C. D. & Wells, W. W. J. biol. Chem. 259, 11890–11894 (1984).

    CAS  PubMed  Google Scholar 

  13. Lipsky, J. J. & Lietman, P. S. Antimicrob. Ag. Chemother. 18, 532–535 (1980).

    Article  CAS  Google Scholar 

  14. Nishizuka, Y. Nature 308, 693–698 (1984).

    Article  ADS  CAS  Google Scholar 

  15. Whitman, M., Epstein, J. & Cantley, L. J. biol. Chem. 259 (in the press).

  16. Streb, H., Irvine, R. F., Berridge, M. J. & Schulz, I. Nature 306, 67–69 (1983).

    Article  ADS  CAS  Google Scholar 

  17. Joseph, S., Thomas, A. P., Williams, R. J., Irvine, R. F. & Williamson, J. R. J. biol. Chem. 259, 3077–3081 (1984).

    CAS  PubMed  Google Scholar 

  18. Burgess, G. M. et al. Nature 309, 63–66 (1984).

    Article  ADS  CAS  Google Scholar 

  19. Kaplan, D. R. et al. Molec. cell. Biol. (submitted).

  20. Carmichael, G. G., Schaffhausen, B. S., Dorsky, D. I., Oliver, D. B. & Benjamin, T. L. Proc. natn. Acad. Sci. U.S.A. 79, 3579–3583 (1982).

    Article  ADS  CAS  Google Scholar 

  21. Benjamin, T. L., Carmichael, G. G. & Schaffhausen, B. S. Cold Spring Harb. Symp. quant. Biol. 44, 263–273 (1980).

    Google Scholar 

  22. Oostra, B. A., Harvey, R., Ely, B. K., Markham, A. F. & Smith, A. E. Nature 304, 456–459 (1983).

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  24. Bolen, J. B. et al. Cell 38, 767–777 (1984).

    Article  CAS  Google Scholar 

  25. Benjamin, T. L. Proc. natn. Acad. Sci. U.S.A. 73, 394–399 (1970).

    Article  ADS  Google Scholar 

  26. Smith, C. C. & Wells, W. W. J. biol. Chem. 258, 9368–9373 (1983).

    CAS  PubMed  Google Scholar 

  27. Seyfred, M. A. & Wells, W. W. J. biol. Chem. 259, 7659–7665 (1984).

    CAS  PubMed  Google Scholar 

  28. Wilson, D. B., Bross, T. E., Hofmann, S. L. and Majerus, P. W. J. biol. Chem. 259, 11718–11724 (1984).

    CAS  PubMed  Google Scholar 

  29. Feunteun, J., Sompayrac, L., Fluck, M. & Benjamin, T. Proc. natn. Acad. Sci. U.S.A. 73, 4169–4173 (1976).

    Article  ADS  CAS  Google Scholar 

  30. Bendig, M., Thomas, T. & Folk, W. J. Virol. 33, 1215–1220 (1980).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Bockus, B., Roberts, T., Parsons, S. & Schaffhausen, B. Molec. cell. Biol. (submitted).

  32. Courtneidge, S. & Smith, A. E. EMBO J. 3, 585–591 (1984).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  34. Parsons, S. J., McCarley, D. J., Ely, C. M., Benjamin, D. C. & Parsons, J. T. J. Virol. 51, 272–282 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts, 02138, USA

    Malcolm Whitman & Lewis Cantley

  2. Laboratory of Neoplastic Disease Mechanisms and Department of Pathology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, 02115, USA

    David R. Kaplan & Thomas M. Roberts

  3. Department of Biochemistry and Pharmacology, Tufts University Medical School, Boston, Massachusetts, 02111, USA

    Brian Schaffhausen

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  1. Malcolm Whitman
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  5. Thomas M. Roberts
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Whitman, M., Kaplan, D., Schaffhausen, B. et al. Association of phosphatidylinositol kinase activity with polyoma middle-T competent for transformation. Nature 315, 239–242 (1985). https://doi.org/10.1038/315239a0

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