Nucleotide sequence of epidermal growth factor cDNA predicts a 128,000-molecular weight protein precursor (original) (raw)

Nature volume 303, pages 722–725 (1983)Cite this article

Abstract

Epidermal growth factor (EGF) has a profound effect on the differentiation of specific cells in vivo, and has been shown to be a potent mitogenic factor for a variety of cultured cells, of both ectodermal and mesodermal origin (see ref. 1 for review). This 53-amino acid polypeptide of known sequence2 contains six cysteine residues3, which are thought to form three intrachain disulphide bonds4. Urogastrone, a polypeptide bearing anti-gastric secretory activity isolated from human urine5, which is presumably synthesized in submandibular and Brunner's glands6,7, shares extensive sequence homology (70%) with EGF and may represent the human EGF equivalent. Here we present the sequence of a mouse EGF cDNA clone, which suggests that EGF is synthesized as a large protein precursor of 1,168 amino acids. Our data indicate that the discrepancy between EGF levels in male and female mouse submaxillary glands (MSGs) is due to different EGF mRNA levels in these tissues, and suggest that precursor EGF processing may differ from that described previously for other polypeptide hormones.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 51 print issues and online access

$199.00 per year

only $3.90 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

References

  1. Carpenter, G. & Cohen, S. A. Rev. Biochem. 48, 193–216 (1979).
    Article CAS Google Scholar
  2. Taylor, J. M., Mitchell, W. M. & Cohen, S. J. biol. Chem. 247, 5928–5934 (1972).
    CAS PubMed Google Scholar
  3. Savage, C. R. Jr, Inagami, T. & Cohen, S. J. biol. Chem. 247, 7612–7621 (1972).
    CAS PubMed Google Scholar
  4. Savage, C. R. Jr, Hash, J. H. & Cohen, S. J. biol. Chem. 248, 7669–7672 (1973).
    CAS PubMed Google Scholar
  5. Gregory, H. Nature 257, 325–327 (1975).
    Article CAS ADS Google Scholar
  6. Elder, J. B., Williams, G., Lacey, E. & Gregory, H. Nature 271, 466–467 (1978).
    Article CAS ADS Google Scholar
  7. Heitz, P. U. et al. Gut 19, 408–413 (1978).
    Article CAS Google Scholar
  8. Wallace, B. et al. Nucleic Acids Res. 9, 879–894 (1981).
    Article CAS Google Scholar
  9. Maxam, A. M. & Gilbert, W. Proc. natn. Acad. Sci. U.S.A. 74, 560–564 (1977).
    Article CAS ADS Google Scholar
  10. Proudfoot, N. J. & Brownlee, G. G. Nature 263, 211–214 (1976).
    Article CAS ADS Google Scholar
  11. Tosi, M., Young, R. A., Hagenbuchle, O. & Schibler, U. Nucleic Acids Res. 9, 2313–2323 (1981).
    Article CAS Google Scholar
  12. Blobel, G. et al., Soc. exp. Biol. Symp. 23, 9–36 (1979).
    Google Scholar
  13. Gregory, H., Walsh, S. & Hopkins, C. R. Gastroenterology 77, 313–318 (1979).
    Article CAS Google Scholar
  14. Noda, M. et al. Nature 295, 202–206 (1982).
    Article CAS ADS Google Scholar
  15. Kakidani, H. et al. Nature 298, 245–249 (1982).
    Article CAS ADS Google Scholar
  16. Nakanishi, S. et al. Nature 278, 423–427 (1979).
    Article CAS ADS Google Scholar
  17. Amara, S. G., Jonmas, V., Rosenfeld, M. G., Ong, E. S. & Evans, R. M. Nature 298, 240–244 (1982).
    Article CAS ADS Google Scholar
  18. Frey, P., Forand, R., Maciag, T. & Shooter, E. M. Proc. natn. Acad. Sci. U.S.A. 76, 6294–6298 (1979).
    Article CAS ADS Google Scholar
  19. Ullrich, A. et al. Science 196, 1313–1317 (1977).
    Article CAS ADS Google Scholar
  20. Dayhoff, M. O. Atlas of Protein Sequence and Structure (National Biomedical Research Foundation, Silver Spring, Maryland, 1978).
    Google Scholar

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Biology, Genentech, Inc., 460 Point San Bruno Boulevard, South San Francisco, California, 94080, USA
    Alane Gray, Thomas J. Dull & Axel Ullrich

Authors

  1. Alane Gray
    You can also search for this author inPubMed Google Scholar
  2. Thomas J. Dull
    You can also search for this author inPubMed Google Scholar
  3. Axel Ullrich
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Gray, A., Dull, T. & Ullrich, A. Nucleotide sequence of epidermal growth factor cDNA predicts a 128,000-molecular weight protein precursor.Nature 303, 722–725 (1983). https://doi.org/10.1038/303722a0

Download citation