Sequence of cDNA encoding human insulin-like growth factor I precursor (original) (raw)

Nature volume 306, pages 609–611 (1983)Cite this article

Abstract

Somatomedins (SM) or insulin-like growth factors (IGF) constitute a heterogeneous group of peptides1 with important growth-promoting effects _in vitro_2,3 as well as _in vivo_4,5. Amino acid sequences have been determined for only two of them, IGF-I and IGF-II, which are highly homologous6,7. IGF-I, which is identical with SM-C8, is composed of 70 amino acid residues and IGF-II contains 73 amino acids and may be identical with SM-A9. Other peptides with different charge properties but with similar SM-like or insulin-like behaviour in biological and receptor assays, have been described but have not yet been fully characterized1. The liver is known to be a major site of production of these peptides10, but many other tissues—especially in the fetus11—may synthesize them as well. We report here the nucleotide sequence of a human liver cDNA encoding the complete amino acid sequence of IGF-I. The IGF-I coding region is flanked by sequences encoding an amino-terminal peptide of at least 25 amino acid residues and a carboxyl-terminal peptide of 35 amino acids. This provides evidence that IGF-I is synthesized as a precursor protein and that formation of IGF-I from this precursor requires proteolytic processing at both ends.

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References

  1. Van den Brande, J. L. & Hoogerbrugge, C. in Growth Hormone and Other Biologically Active Peptides (eds Pecile, A. & Müller, E. E.) 81–102 (Excerpta Medica, Amsterdam 1980).
    Google Scholar
  2. Daughaday, W. H. Clin. endocr. Metab. 6, 117–135 (1977).
    Article CAS Google Scholar
  3. Clemmons, D. R. & Van Wyk, J. J. J. cell. Phys. 106, 361–367 (1981).
    Article CAS Google Scholar
  4. van Buul-Offers, S. & Van den Brande, J. L. in Growth Hormone and Other Biologically Active Peptides (eds Pecile, A. & Müller, E. E.) 103–122 (Excerpta Medica, Amsterdam 1980).
    Google Scholar
  5. Schoenle, E. et al. Nature 296, 252–253 (1982).
    Article ADS CAS PubMed Google Scholar
  6. Rinderknecht, E. & Humbel, R. E. FEBS Lett. 89, 283–286 (1978).
    Article CAS PubMed Google Scholar
  7. Rinderknecht, E. & Humbel, R. E. J. biol. Chem. 253, 2769–2775 (1978).
    CAS PubMed Google Scholar
  8. Klapper, D. G., Svoboda, M. E. & Van Wyk, J. J. Endocrinology 112, 2215–2217 (1983).
    Article CAS PubMed Google Scholar
  9. Fryklund, L., Uthne, K. & Sievertsson, H. Biochem. biophys. Res. Commun. 61, 957–962 (1974).
    Article CAS PubMed Google Scholar
  10. Phillips, L. S. et al. Endocrinology 98, 606–614 (1976).
    Article CAS PubMed Google Scholar
  11. D'Ercole, A. J., Applewhite, G. T. & Underwood, L. E. Devl Biol. 75, 315–329 (1980).
    Article CAS Google Scholar
  12. Woods, D. E. et al. Proc. natn. Acad. Sci. U.S.A. 79, 5661–5665 (1982).
    Article ADS CAS Google Scholar
  13. Talmadge, K., Stahl, S. & Gilbert, W. Proc. natn. Acad. Sci. U.S.A. 77, 3369–3373 (1980).
    Article ADS CAS Google Scholar
  14. Casadavan, M. & Cohen, S. N. J. molec. Biol. 138, 179–207 (1980).
    Article Google Scholar
  15. Breslow, J. L. et al. Proc. natn. Acad. Sci. U.S.A. 79, 6861–6865 (1982).
    Article ADS CAS Google Scholar
  16. Maxam, A. M. & Gilbert, W. Proc. natn. Acad. Sci. U.S.A. 74, 560–564 (1977).
    Article ADS CAS Google Scholar
  17. Maxam, A. M. & Gilbert, W. Meth. Enzym. 65, 499–560 (1980).
    Article CAS PubMed Google Scholar
  18. Hudson, P. et al. Nature 291, 127–131 (1981).
    Article ADS CAS PubMed Google Scholar
  19. Hagenbüchle, O., Santer, M. & Steitz, J. A. Cell 13, 551–563 (1978).
    Article PubMed Google Scholar
  20. Sargan, D. R., Gregory, S. P. & Butterworth, P. H. W. FEBS Lett. 147, 133–136 (1982).
    Article CAS PubMed Google Scholar
  21. Erni, B. & Stachelin, T. FEBS Lett. 148, 79–82 (1982).
    Article CAS PubMed Google Scholar
  22. Blobel, G. & Doberstein, B. J. Cell Biol. 67, 852–862 (1975).
    Article CAS PubMed Google Scholar
  23. Aquaviva, M. A. et al. Diabetes 31, 656–658 (1982).
    Article Google Scholar
  24. Vassilopoulou-Sellin, R. & Phillips, L. S. Endocrinology 110, 582–589 (1982).
    Article CAS PubMed Google Scholar
  25. Craig, R. K. et al. Nature 295, 345–347 (1982).
    Article ADS CAS PubMed Google Scholar
  26. MacIntyre, I. et al. Nature 300, 460–462 (1982).
    Article ADS CAS PubMed Google Scholar
  27. Bell, G. I. et al. Nature 282, 525–527 (1979).
    Article ADS CAS PubMed Google Scholar
  28. Hudson, P. et al. Nature 301, 628–631 (1983).
    Article ADS CAS PubMed Google Scholar
  29. Smith, D. R. & Calvo, T. M. Nucleic Acids Res. 8, 2255–2274 (1980).
    Article CAS PubMed PubMed Central Google Scholar

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Authors and Affiliations

  1. Department of Pediatrics, State University of Utrecht, The Netherlands
    M. Jansen & J. L. Van den Brande
  2. Laboratory for Physiological Chemistry, State University of Utrecht, The Netherlands
    F. M. A. van Schaik & J. S. Sussenbach
  3. Department of Medicine, Children's Hospital Medical Center, Boston, Massachusetts, 02115, USA
    A. T. Ricker, B. Bullock, D. E. Woods & K. H. Gabbay
  4. Harvard Medical School, Boston, Massachusetts, 02115, USA
    A. T. Ricker, B. Bullock, D. E. Woods, K. H. Gabbay & A. L. Nussbaum

Authors

  1. M. Jansen
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  2. F. M. A. van Schaik
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  3. A. T. Ricker
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  4. B. Bullock
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  5. D. E. Woods
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  6. K. H. Gabbay
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  7. A. L. Nussbaum
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  8. J. S. Sussenbach
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  9. J. L. Van den Brande
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Jansen, M., van Schaik, F., Ricker, A. et al. Sequence of cDNA encoding human insulin-like growth factor I precursor.Nature 306, 609–611 (1983). https://doi.org/10.1038/306609a0

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