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Cloning of the gene and cDNA for mammalian β-adrenergic receptor and homology with rhodopsin

Abstract

The adenylate cyclase system, which consists of a catalytic moiety and regulatory guanine nucleotide-binding proteins, provides the effector mechanism for the intracellular actions of many hormones and drugs1. The tissue specificity of the system is determined by the particular receptors that a cell expresses. Of the many receptors known to modulate adenylate cyclase activity, the best characterized and one of the most pharmacologically important is the β-adrenergic receptor (βAR). The pharmacologically distinguishable subtypes of the β-adrenergic receptor, β1 and β2 receptors, stimulate adenylate cyclase on binding specific catecholamines1. Recently, the avian erythrocyte β1, the amphibian erythrocyte β2 and the mammalian lung β2 receptors have been purified to homogeneity and demonstrated to retain binding activity in detergent-solubilized form1–5. Moreover, the β-adrenergic receptor has been reconstituted with the other components of the adenylate cyclase system in vitro6, thus making this hormone receptor particularly attractive for studies of the mechanism of receptor action. This situation is in contrast to that for the receptors for growth factors and insulin, where the primary biochemical effectors of receptor action are unknown. Here, we report the cloning of the gene and cDNA for the mammalian β2AR. Analysis of the amino-acid sequence predicted for the βAR indicates significant amino-acid homology with bovine rhodopsin and suggests that, like rhodopsin7, βAR possesses multiple membrane-spanning regions.

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References

  1. Lefkowitz, R. J., Stadel, J. M. & Caron, M. G. A. Rev. Biochem. 52, 159–186 (1983).

    Article  CAS  Google Scholar 

  2. Shorr, R. G., Lefkowitz, R. J. & Caron, M. G. J. biol. Chem. 256, 5820–5826 (1981).

    CAS  PubMed  Google Scholar 

  3. Shorr, R. G., Strohsacker, M. W., Lavin, T. N., Lefkowitz, R. J. & Caron, M. G. J. biol. Chem. 257, 12341–12350 (1982).

    CAS  PubMed  Google Scholar 

  4. Homcy, C. J., Rockson, S. G., Countaway, J. & Egan, D. A. Biochemistry 22, 660–668 (1983).

    Article  CAS  PubMed  Google Scholar 

  5. Benovic, J. L., Shorr, R. G. L., Caron, M. G. & Lefkowitz, R. J. Biochemistry 23, 4510–4518 (1984).

    Article  CAS  PubMed  Google Scholar 

  6. Cerione, R. A. et al. J. biol. Chem. 259, 9979–9982 (1984).

    CAS  PubMed  Google Scholar 

  7. Engelman, D. M., Goldman, A. & Steitz, T. A. Meth. Enzym. 88, 81–88 (1982).

    Article  CAS  Google Scholar 

  8. Temeles, G. L., Gibbs, J. B., D'Alonzo, J. S., Sigal, I. S. & Scolnick, E. M. Nature 313, 700–703 (1985).

    Article  ADS  CAS  PubMed  Google Scholar 

  9. Seidah, N. G. et al. Proc. natn. Acad. Sci. U.S.A. 81, 2640–2644 (1984).

    Article  ADS  CAS  Google Scholar 

  10. Delavier-Klutchko, C., Hocheke, J. & Strasberg, A. D. FEBS Lett. 169, 151–155 (1984).

    Article  CAS  PubMed  Google Scholar 

  11. Stiles, G. L., Benovic, J. L., Caron, M. G. & Lefkowitz, R. J. J. biol. Chem. 259, 8655–8663 (1984).

    CAS  PubMed  Google Scholar 

  12. Hopp, T. P. & Woods, K. R. Proc. natn. Acad. Sci. U.S.A. 78, 3824–3828 (1981).

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  14. Nathans, J. & Hogness, D. S. Cell 34, 807–814 (1983).

    Article  CAS  PubMed  Google Scholar 

  15. Hubbell, W. L. & Bownds, M. D. A. Rev. Neurosci. 2, 17–34 (1979).

    Article  CAS  Google Scholar 

  16. Stryer, L. A. Rev. Neurosci. 9, 87–119 (1986).

    Article  CAS  Google Scholar 

  17. Gilman, A. G. Cell 36, 577–579 (1984).

    Article  CAS  PubMed  Google Scholar 

  18. Margrave, P. A. Prog. Retinal Res. 1, 1–51 (1982).

    Article  Google Scholar 

  19. Benovic, J. L., Strasser, R. H., Caron, M. G. & Lefkowitz, R. J. Proc. natn. Acad. Sci. U.S.A. (in the press).

  20. Benovic, J. L. et al. J. biol. Chem. 260, 7094–7101 (1985).

    CAS  PubMed  Google Scholar 

  21. Thomas, D. D. & Stryer, L. J. molec. Biol. 154, 145–157 (1982).

    Article  PubMed  Google Scholar 

  22. Caron, M. G. & Lefkowitz, R. J. J. biol. Chem. 251, 2374–2384 (1976).

    CAS  PubMed  Google Scholar 

  23. Hewick, R. M., Hunkapiller, M. W., Hood, L. E. & Dreyer, W. J. J. biol. Chem. 256, 7790–7797 (1981).

    Google Scholar 

  24. Spiess, J., Rivier, J. E., Rodkey, J. A., Bennett, C. D. & Vale, W. Proc. natn. Acad. Sci. U.S.A. 76, 2974–2978 (1979).

    Article  ADS  CAS  Google Scholar 

  25. Laemmli, U. K. Nature 117, 680–685 (1970).

    Article  ADS  Google Scholar 

  26. Towbin, H., Staehelin, T. & Gordon, J. Proc. natn. Acad. Sci. U.S.A. 76, 4350–4356 (1979).

    Article  ADS  CAS  Google Scholar 

  27. Johnson, D. A. & Elder, J. H. J. exp. Med. 159, 1751–1756 (1983).

    Article  Google Scholar 

  28. Maniatis, T., Fritsch, E. F. & Sambrook, J. Molecular Cloning, A Laboratory Manual (Cold Spring Harbor Laboratory, New York, 1982).

    Google Scholar 

  29. Merrifield, R. B. J. Am. chem. Soc. 85, 2149–2154 (1963).

    Article  CAS  Google Scholar 

  30. Frischauf, A. M., Lehrach, H., Paustka, A. & Murray, N. J. molec. Biol. 170, 827–842 (1983).

    Article  CAS  PubMed  Google Scholar 

  31. Lauffer, L. et al. Nature 318, 334–338 (1985).

    Article  ADS  CAS  PubMed  Google Scholar 

  32. Benton, W. D. & Davis, R. W. Science 196, 180–182 (1977).

    Article  ADS  CAS  PubMed  Google Scholar 

  33. Ullrich, A., Berman, C. H., Dull, T. J., Gray, A. & Lee, J. M. EMBO J. 3, 361–364 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Southern, E. M. J. molec. Biol. 98, 503–517 (1975).

    Article  CAS  PubMed  Google Scholar 

  35. Maxam, A. M. & Gilbert, W. Proc. natn. Acad. Sci. U.S.A. 74, 560–565 (1977).

    Article  ADS  CAS  Google Scholar 

  36. Vieira, J. & Messing, J. Gene 19, 259–268 (1982).

    Article  CAS  PubMed  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  38. Schaffner, W. et al. Cell 14, 655–671 (1978).

    Article  CAS  PubMed  Google Scholar 

  39. Nagata, S., Mantei, N. & Weissman, C. Nature 287, 401–408 (1980).

    Article  ADS  CAS  PubMed  Google Scholar 

  40. Lawn, R. M. et al. Nucleic Acids Res. 9, 1045–1052 (1981).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  41. Volckaert, G., Feunteun, J., Crawford, L. V., Berg, P. & Fiers, W. J. J. Virol. 30, 674–682 (1979).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Hamer, D. H. & Leder, P. Cell 18, 1299–1302 (1979).

    Article  CAS  PubMed  Google Scholar 

  43. Kozak, M. Nucleic Acids Res. 12, 857–872 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Green, S. et al. Nature 320, 134–139 (1986).

    Article  ADS  CAS  PubMed  Google Scholar 

  45. Friedlander, M. & Blobel, G. Nature 318, 338–343 (1985).

    Article  ADS  CAS  PubMed  Google Scholar 

  46. Feramisco, J. L., Glass, D. B. & Krebs, E. G. J. biol. Chem. 255, 4240–4245 (1980).

    CAS  PubMed  Google Scholar 

  47. Chirgwin, J. M., Przybyla, A. E., MacDonald, R. J. & Rutter, W. J. Biochemistry 18, 5294–5299 (1979).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  49. Huynh, T. V., Young, R. A. & Davis, R. W. in DNA Cloning a Practical Approach Vol. 1, 49–78 (IRL, Oxford, 1985).

    Google Scholar 

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Dixon, R., Kobilka, B., Strader, D. et al. Cloning of the gene and cDNA for mammalian β-adrenergic receptor and homology with rhodopsin. Nature 321, 75–79 (1986). https://doi.org/10.1038/321075a0

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