Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

A single human gene encoding multiple tyrosine hydroxylases with different predicted functional characteristics

Abstract

Catecholaminergic systems in discrete regions of the brain are thought to be important in affective psychoses, learning and memory, reinforcement and sleep–wake cycle regulation1. Tyrosine hydroxylase (TH) is the first enzyme in the pathway of catecholamine synthesis. Its importance is reflected in the diversity of the mechanisms that have been described which control its activity2; TH levels vary both during development and as a function of the activity of the nervous system. Recently, we deduced the complete amino-acid sequence of rat TH from a complementary DNA clone encoding a functional enzyme3,4. Here we demonstrate that, in man, TH molecules are encoded by at least three distinct messenger RNAs. The expression of these mRNAs varies in different parts of the nervous system. The sequence differences observed are confined to the 5′ termini of the messengers and involve alternative splicing events. This variation has clear functional consequences for each putative form of the enzyme and could represent a novel means of regulating catecholamine levels in normal and pathological neurons.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Similar content being viewed by others

References

  1. Cooper, J. R., Bloom, F. E. & Roth, R. H. The Biochemical Basis of Neuropharmacology (Oxford University Press, 1982).

    Google Scholar 

  2. Zigmond, R. E. Trends Neurosci. 8, 63–69 (1985).

    Article  CAS  Google Scholar 

  3. Grima, B., Lamouroux, A., Blanot, F., Faucon Biguet, N. & Mallet, J. Proc. natn. Acad. Sci. U.S.A. 82, 617–621 (1985).

    Article  ADS  CAS  Google Scholar 

  4. Horellou, P., Guibert, B., Leviel, V. & Mallet, J. FEBS Lett. 205, 6–10 (1986).

    Article  CAS  Google Scholar 

  5. Gubler, U. & Hoffman, B. J. Gene 25, 263–269 (1983).

    Article  CAS  Google Scholar 

  6. Mount, S. M. Nucleic Acids Res. 10, 459–472 (1982).

    Article  CAS  Google Scholar 

  7. Nabeshima, Y., Fujii-Kuriyama, Y., Muramatsu, M. & Ogata, K. Nature 308, 333–338 (1984).

    Article  ADS  CAS  Google Scholar 

  8. Stanley, E., Metcalf, D., Sobieszczuk, P., Gongh, N. M. & Dunn, A. R. EMBO J. 4, 2569–2573 (1985).

    Article  CAS  Google Scholar 

  9. Berod, A., Faucon Biguet, N., Dumas, S., Block, B. & Mallet, J. Proc. natn. Acad. Sci. U.S.A. (in the press).

  10. Joh, T. H. & Reis, D. J. Brain Res. 85, 146–151 (1975).

    Article  CAS  Google Scholar 

  11. Oka, K., Ashiba, G., Sugimoto, T., Matsuura, S. & Nagatsu, T. Biochim. biophys. Acta 706, 188–196 (1982).

    Article  CAS  Google Scholar 

  12. Acheson, A. L., Kapatos, G. & Zigmond, M. J. Life Sci. 28, 1407–1420 (1981).

    Article  CAS  Google Scholar 

  13. Mallet, J. et al. in The Role of RNA and DNA in Brain Function; a Molecular Biological Approach (eds Giuditta, A., Kaplan, B. & Zonzely-Neurath, C.) 57–70 (Nijhoff, Boston, 1986).

    Book  Google Scholar 

  14. Campbell, D. G., Hardie, D. G. & Vulliet, P. R. J. biol. Chem. 261, 10489–10492 (1986).

    CAS  PubMed  Google Scholar 

  15. Pearson, R. B., Woodgett, J. R., Cohen, P. & Kemp, B. E. J. biol. Chem. 260, 14471–14476 (1985).

    CAS  PubMed  Google Scholar 

  16. Cohen, P. Eur. J. Biochem. 151, 439–448 (1985).

    Article  CAS  Google Scholar 

  17. Treiman, M., Weber, W. & Gratzl, M. J. Neurochem. 40, 661–669 (1983).

    Article  CAS  Google Scholar 

  18. Faucon Biguet, N., Buda, M., Lamouroux, A., Samolyk, D. & Mallet, J. EMBO J. 1, 287–291 (1986).

    Article  Google Scholar 

  19. Lewander, T., Joh, T. H. & Reis, D. J. Nature 258, 440–441 (1975).

    Article  ADS  CAS  Google Scholar 

  20. Bokobza, B., Ruberg, M., Scatton, B., Javoy-Agid, F. & Agid, Y. Eur. J. Pharmac. 99, 167–175 (1984).

    Article  CAS  Google Scholar 

  21. Craig, S. P., Buckle, V. J., Lamouroux, A., Mallet, J. & Craig, I. W. Cytogenet. Cell Genet. 42, 29–32 (1986).

    Article  CAS  Google Scholar 

  22. Moss, P. A. H., Davies, K. E., Boni, C., Mallet, J. & Reeders, S. T. Nucleic Acids Res. 14, 9927–9932 (1986).

    Article  CAS  Google Scholar 

  23. Egeland, J. A. et al. Nature 325, 783–787 (1987).

    Article  ADS  CAS  Google Scholar 

  24. Montminy, M. R., Sevarino, K. A., Wagner, J. A., Mandel, G. & Goodman, R. H. Proc. natn. Acad. Sci. U.S.A. 83, 6682–6686 (1986).

    Article  ADS  CAS  Google Scholar 

  25. Comb, M., Birnberg, N. C., Seasholtz, A., Herbert, E. & Goodman, H. M. Nature 323, 353–356 (1986).

    Article  ADS  CAS  Google Scholar 

  26. Lomedico, P. & Saunders, G. Nucleic Acids Res. 3, 381–391 (1976).

    Article  CAS  Google Scholar 

  27. Huynh, T. V., Young, R. A. & Davis, R. W. in DNA Cloning Techniques: a Practical Approach Vol. I (ed. Glover, D.) 49–78 (IRL Press, Oxford, 1984).

    Google Scholar 

  28. Grosveld, F. G. et al. Nucleic Acids Res. 10, 6715–6732 (1982).

    Article  CAS  Google Scholar 

  29. Grosveld, F. G., Dahl, H. H. M., De Boer, E. & Flavell, R. A. Gene 13, 227–237 (1981).

    Article  CAS  Google Scholar 

  30. Sanger, F., Nicklen, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).

    Article  ADS  CAS  Google Scholar 

  31. McKnight, S. L. & Kingsbury, R. Science 217, 316–324 (1982).

    Article  ADS  CAS  Google Scholar 

  32. Berk, A. J. & Sharp, P. A. Cell 12, 721–732 (1977).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Grima, B., Lamouroux, A., Boni, C. et al. A single human gene encoding multiple tyrosine hydroxylases with different predicted functional characteristics. Nature 326, 707–711 (1987). https://doi.org/10.1038/326707a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/326707a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing