Cloning and sequence analysis of a cDNA for rat transforming growth factor-α (original) (raw)

Nature volume 313, pages 489–491 (1985)Cite this article

Abstract

Transforming growth factors (TGFs) are mitogenic polypeptides produced most conspicuously by transformed cells and conferring on normal cells several phenotypic alterations associated with transformation1,2. TGFs comprise two distinct sets of molecules: TGF-_α_s are structurally similar to epidermal growth factor (EGF), binding to and inducing the tyrosine phosphorylation of the EGF receptor in a manner indistinguishable from that of EGF3. In addition, the 50-amino acid rat TGF-_α_4 has 33 and 44% homologies with mouse5 and human6 EGFs, respectively, and shares with EGFs a conserved pattern of three disulphide bridges7. Thus, it has been proposed that TGF-_α_s belong to a family of EGF-like polypeptides7. TGF-_β_s, on the other hand, display no measurable binding to EGF receptors, but potentiate the growth stimulating activities of TGF-_α_8. Here we report the isolation of a complementary DNA clone encoding rat TGF-α. This cDNA hybridizes to a 4.5-kilobase (kb) messenger RNA that is 30 times larger than necessary to code for a 50-amino acid polypeptide and is present not only in retrovirus-transformed rat cells but also at lower levels in normal rat tissues. The nucleotide sequence of the cDNA predicts that TGF-α is synthesized as a larger product and that the larger form may exist as a transmembrane protein. However, unlike many polypeptide hormones (including EGF9,10), cleavage of the 50-amino acid TGF-α from the larger form does not occur at paired basic residues, but rather between alanine and valine residues, suggesting the role of a novel protease.

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References

  1. Todaro, G. J., DeLarco, J. E., Fryling, C., Johnson, P. A. & Sporn, M. B. J. supramolec. Struct. 15, 287–301 (1981).
    CAS Google Scholar
  2. DeLarco, J. E. & Todaro, G. J. Proc. natn. Acad. Sci. U.S.A. 75, 4001–4005 (1978).
    Article ADS CAS Google Scholar
  3. Pike, L. J. et al. J. biol. Chem. 257, 14628–14631 (1983).
    Google Scholar
  4. Marquardt, H. et al. Proc. natn. Acad. Sci. U.S.A. 80, 4684–4688 (1983).
    Article ADS CAS Google Scholar
  5. Savage, C. R. Jr, Inagami, T. & Cohen, S. J. biol. Chem. 247, 7612–7621 (1972).
    CAS PubMed Google Scholar
  6. Gregory, H. Nature 257, 325–327 (1975).
    Article ADS CAS Google Scholar
  7. Marquardt, H., Hunkapiller, H. W., Hood, L. E. & Todaro, G. J. Science 223, 1079–1082 (1984).
    Article ADS CAS Google Scholar
  8. Anzano, M. A. et al. Cancer Res. 42, 4776–4778 (1982).
    CAS PubMed Google Scholar
  9. Gray, A., Dull, T. J. & Ullrich, A. Nature 303, 722–725 (1983).
    Article ADS CAS Google Scholar
  10. Scott, J. et al. Science 221, 236–240 (1983).
    Article ADS CAS Google Scholar
  11. Twardzik, D. R., Todaro, G. J., Reynolds, F. H. Jr & Stephenson, J. R. Virology 124, 201–207 (1983).
    Article CAS Google Scholar
  12. Huynh, T., Young, R. & Davis, R. in Practical Approaches in Biochemistry (ed. Glover, D.) (IRL, Oxford, 1984).
    Google Scholar
  13. Dente, L., Cesareni, G. & Cortese, R. Nucleic Acids Res. 11, 1645–1655 (1983).
    Article CAS Google Scholar
  14. Linsley, P. S., Hargreaves, W. R., Twardzik, D. R. & Todaro, G. J. Proc. natn. Acad. Sci. U.S.A. (in the press).
  15. Naughton, M. A. & Sanger, F. Biochem. J. 78, 156–162 (1961).
    Article CAS Google Scholar
  16. Matsubara, H. Meth. Enzym. 19, 642–651 (1970).
    Article Google Scholar
  17. Kreil, G. A. Rev. Biochem. 50, 317–348 (1981).
    Article CAS Google Scholar
  18. Okayama, H. & Berg, P. Molec. cell. Biol. 2, 161–167 (1982).
    Article CAS Google Scholar
  19. Smith, A. J. H. Meth. Enzym. 65, 560–580 (1980).
    Article ADS CAS Google Scholar
  20. Glisin, V., Crkvenjakov, R. & Byns, C. Biochemistry 13, 2633–2638 (1974).
    Article CAS Google Scholar
  21. Chirgwin, J. M., Przybyla, A. E., MacDonald, R. J. & Rutter, W. J. Biochemistry 18, 5294–5299 (1979).
    Article CAS Google Scholar
  22. Maniatis, T., Fritsch, E. F. & Sambrook, J. in Molecular Cloning (Cold Spring Harbor Laboratory, New York, 1982).
    Google Scholar
  23. Southern, E. M. J. molec. Biol. 98, 503–517 (1975).
    Article CAS Google Scholar
  24. Brown, J. P., Twardzik, D. R., Marquardt, H. & Todaro, G. J. Nature 313, 491–492 (1985).
    Article ADS CAS Google Scholar
  25. Derynck, R., Roberts, A. B., Winkler, M. E., Chen, E. Y. & Goeddel, D. V. Cell 38, 287–297 (1984).
    Article CAS Google Scholar

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Authors and Affiliations

  1. Oncogen, 3005 First Avenue, Seattle, Washington, 98121, USA
    David C. Lee, Timothy M. Rose, Nancy R. Webb & George J. Todaro
  2. Department of Pathology, University of Washington, School of Medicine, Seattle, Washington, 98195, USA
    George J. Todaro

Authors

  1. David C. Lee
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  2. Timothy M. Rose
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  3. Nancy R. Webb
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  4. George J. Todaro
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Lee, D., Rose, T., Webb, N. et al. Cloning and sequence analysis of a cDNA for rat transforming growth factor-α.Nature 313, 489–491 (1985). https://doi.org/10.1038/313489a0

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