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:

Alternative splicing of C-terminal tail of prostaglandin E receptor subtype EP3 determines G-protein specificity

Abstract

PEPTIDE hormones, neurotransmitters, and autacoids activate a family of seven-transmembrane-domain receptors1. Each of these receptors specifically couples to one of several G proteins, Gs, Gi, Go and Gp, to activate a specific second messenger system2. Cell surface receptors for prostanoids have been characterized pharmacologically3 and the complementary DNAs for thrombox-ane A2 receptor4,5 and the EP3 subtype of the prostaglandin (PG)E receptor6 reveal that they belong to the seven-transmembrane-domain receptor family. The EP3 receptor mediates the diverse physiological actions of PGE2 (ref. 3). Although most of them occur through coupling of the EP3 receptor to Gi and inhibition of adenylyl cyclase, the EP3-mediated contraction of uterine muscle can only occur by activation of another second messenger pathway7. In chromaffin cells, two different second messenger pathways are activated by PGE2 binding to an apparently single EP3 receptor class8. Here we show that at least four isoforms of the EP3 receptor, which differ only at their C-terminal tails and are produced by alternative splicing, couple to different G proteins to activate different second messenger systems.

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. O'Dowd, B. F., Lefkowitz, R. J. & Caron, M. G. A. Rev. Neurosci. 12, 67–83 (1989).

    Article  CAS  Google Scholar 

  2. Gilman, A. G. A. Rev. Biochem. 56, 615–649 (1987).

    Article  CAS  Google Scholar 

  3. Coleman, R. A., Kennedy, I., Humphrey, P. P. A., Bunce, K. & Lumley, P. in Comprehensive Medicinal Chemistry Vol. 3 (ed. Emmett, J. C.) 643–714 (Pergamon, Oxford, 1990).

    Google Scholar 

  4. Hirata, M. et al. Nature 349, 617–620 (1991).

    Article  ADS  CAS  Google Scholar 

  5. Namba, T. et al. Biochem. biophys. Res. Commun. 184, 1197–1203 (1992).

    Article  CAS  Google Scholar 

  6. Sugimoto, Y. et al. J. biol. Chem. 267, 6463–6466 (1992).

    CAS  PubMed  Google Scholar 

  7. Goureau, O., Tanfin, Z., Marc, S. & Harbon, S. Am. J. Physiol. 263, C257–C265 (1992).

    Article  CAS  Google Scholar 

  8. Negishi, M., Ito, S. & Hayaishi, O. J. biol. Chem. 264, 3916–3923 (1989).

    CAS  PubMed  Google Scholar 

  9. Padgett, R. A., Grabowski, P. J., Konarska, M. M., Seiler, S. & Sharp, P. A. A. Rev. Biochem. 55, 1119–1150 (1986).

    Article  CAS  Google Scholar 

  10. Negishi, M. et al. J. biol. Chem. 262, 12077–12084 (1987).

    CAS  PubMed  Google Scholar 

  11. Federman, A. D., Conklin, B. R., Schrader, K. A., Reed, R. R. & Bourne, H. R. Nature 356, 159–161 (1992).

    Article  ADS  CAS  Google Scholar 

  12. O'Dowd, B. F. et al. J. biol. Chem. 263, 15985–15992 (1988).

    CAS  PubMed  Google Scholar 

  13. Hausdorff, W. P., Hnatowich, M., O'Dowd, B. F., Caron, M. G. & Lefkowitz, R. J. J. biol. Chem. 265, 1388–1393 (1990).

    CAS  PubMed  Google Scholar 

  14. Franke, R. R., König, B., Sakmar, T. P., Khorana, H. G. & Hofmann, K. P. Science 250, 123–125 (1990).

    Article  ADS  CAS  Google Scholar 

  15. Okamoto, T. et al. Cell 67, 723–730 (1991).

    Article  CAS  Google Scholar 

  16. Okamoto, T. & Nishimoto, I. J. biol. Chem. 267, 8342–8346 (1992).

    CAS  PubMed  Google Scholar 

  17. Ikezu, T., Okamoto, T., Ogata, E. & Nishimoto, I. FEBS Lett. 311, 29–32 (1992).

    Article  CAS  Google Scholar 

  18. Cotecchia, S., Exum, S., Caron, M. G. & Lefkowitz, R. J. Proc. natn. Acad. Sci. U.S.A. 87, 2896–2900 (1990).

    Article  ADS  CAS  Google Scholar 

  19. O'Dowd, B. F., Hnatowich, M., Caron, M. G., Lefkowitz, R. J. & Bouvier, M. J. biol. Chem. 264, 7564–7569 (1989).

    CAS  PubMed  Google Scholar 

  20. Giros, B. et al. Nature 342, 923–926 (1989).

    Article  ADS  CAS  Google Scholar 

  21. Monsma, F. J., McVittie, L. D., Gerfen, C. R., Mahan, L. C. & Sibley, D. R. Nature 342, 926–929 (1989).

    Article  ADS  CAS  Google Scholar 

  22. Dal Toso, R. et al. EMBO J. 8, 4025–4034 (1989).

    Article  CAS  Google Scholar 

  23. Tanabe, Y., Masu, M., Ishii, T., Shigemoto, R. & Nakanishi, S. Neuron 8, 169–179 (1992).

    Article  CAS  Google Scholar 

  24. Fong, T. M., Anderson, S. A., Yu, H., Huang, R.-R. C. & Strader, C. D. Molec. Pharmac. 41, 24–30 (1992).

    CAS  Google Scholar 

  25. Sugimoto, Y. et al. J. biol. Chem. 268, 2712–2718 (1993).

    CAS  PubMed  Google Scholar 

  26. Kyte, J. & Doolittle, R. F. J. molec. Biol. 157, 105–132 (1982).

    Article  CAS  Google Scholar 

  27. Oikawa, S. et al. Biochem. biophys. Res. Commun. 164, 39–45 (1989).

    Article  CAS  Google Scholar 

  28. Felgner, P. L. et al. Proc. natn. Acad. Sci. U.S.A. 84, 7413–7417 (1987).

    Article  ADS  CAS  Google Scholar 

  29. Okajima, F., Katada, T. & Ui, M. J. biol. Chem. 260, 6761–6768 (1985).

    CAS  PubMed  Google Scholar 

  30. Ito, S. et al. J. Neurochem. 56, 531–540 (1991).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Namba, T., Sugimoto, Y., Negishi, M. et al. Alternative splicing of C-terminal tail of prostaglandin E receptor subtype EP3 determines G-protein specificity. Nature 365, 166–170 (1993). https://doi.org/10.1038/365166a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/365166a0

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