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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. 1.

    , & A. Rev. Biochem. 52, 159–186 (1983).

  2. 2.

    , & J. biol. Chem. 256, 5820–5826 (1981).

  3. 3.

    , , , & J. biol. Chem. 257, 12341–12350 (1982).

  4. 4.

    , , & Biochemistry 22, 660–668 (1983).

  5. 5.

    , , & Biochemistry 23, 4510–4518 (1984).

  6. 6.

    et al. J. biol. Chem. 259, 9979–9982 (1984).

  7. 7.

    , & Meth. Enzym. 88, 81–88 (1982).

  8. 8.

    , , , & Nature 313, 700–703 (1985).

  9. 9.

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

  10. 10.

    , & FEBS Lett. 169, 151–155 (1984).

  11. 11.

    , , & J. biol. Chem. 259, 8655–8663 (1984).

  12. 12.

    & Proc. natn. Acad. Sci. U.S.A. 78, 3824–3828 (1981).

  13. 13.

    & J. molec. Biol. 157, 105–132 (1982).

  14. 14.

    & Cell 34, 807–814 (1983).

  15. 15.

    & A. Rev. Neurosci. 2, 17–34 (1979).

  16. 16.

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

  17. 17.

    Cell 36, 577–579 (1984).

  18. 18.

    Prog. Retinal Res. 1, 1–51 (1982).

  19. 19.

    , , & Proc. natn. Acad. Sci. U.S.A. (in the press).

  20. 20.

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

  21. 21.

    & J. molec. Biol. 154, 145–157 (1982).

  22. 22.

    & J. biol. Chem. 251, 2374–2384 (1976).

  23. 23.

    , , & J. biol. Chem. 256, 7790–7797 (1981).

  24. 24.

    , , , & Proc. natn. Acad. Sci. U.S.A. 76, 2974–2978 (1979).

  25. 25.

    Nature 117, 680–685 (1970).

  26. 26.

    , & Proc. natn. Acad. Sci. U.S.A. 76, 4350–4356 (1979).

  27. 27.

    & J. exp. Med. 159, 1751–1756 (1983).

  28. 28.

    , & Molecular Cloning, A Laboratory Manual (Cold Spring Harbor Laboratory, New York, 1982).

  29. 29.

    J. Am. chem. Soc. 85, 2149–2154 (1963).

  30. 30.

    , , & J. molec. Biol. 170, 827–842 (1983).

  31. 31.

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

  32. 32.

    & Science 196, 180–182 (1977).

  33. 33.

    , , , & EMBO J. 3, 361–364 (1984).

  34. 34.

    J. molec. Biol. 98, 503–517 (1975).

  35. 35.

    & Proc. natn. Acad. Sci. U.S.A. 74, 560–565 (1977).

  36. 36.

    & Gene 19, 259–268 (1982).

  37. 37.

    , & Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).

  38. 38.

    et al. Cell 14, 655–671 (1978).

  39. 39.

    , & Nature 287, 401–408 (1980).

  40. 40.

    et al. Nucleic Acids Res. 9, 1045–1052 (1981).

  41. 41.

    , , , & J. Virol. 30, 674–682 (1979).

  42. 42.

    & Cell 18, 1299–1302 (1979).

  43. 43.

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

  44. 44.

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

  45. 45.

    & Nature 318, 338–343 (1985).

  46. 46.

    , & J. biol. Chem. 255, 4240–4245 (1980).

  47. 47.

    , , & Biochemistry 18, 5294–5299 (1979).

  48. 48.

    & Gene 25, 263–269 (1983).

  49. 49.

    , & in DNA Cloning a Practical Approach Vol. 1, 49–78 (IRL, Oxford, 1985).

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Affiliations

  1. Department of Virus and Cell Biology Research, Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania 19486, USA

    • Richard A. F. Dixon
    • , Elaine Rands
    • , Ronald E. Diehl
    •  & Irving S. Sigal
  2. Departments of Medicinal Chemistry, Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania 19486, USA

    • Carl D. Bennett
  3. Howard Hughes Medical Institute, Department of Medicine, Biochemistry and Physiology, Duke University Medical Center, Durham, North Carolina 27710, USA

    • Brian K. Kobilka
    • , Jeffrey L. Benovic
    • , Henrik G. Dohlman
    • , Thomas Frielle
    • , Mark A. Bolanowski
    • , Marc G. Caron
    •  & Robert J. Lefkowitz
  4. Department of Biochemistry and Molecular Biology, Merck Sharp and Dohme Research Laboratories, Rahway, New Jersey 07065, USA

    • David J. Strader
    • , Richard A. Mumford
    • , Eve E. Slater
    •  & Catherine D. Strader

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https://doi.org/10.1038/321075a0

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