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

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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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Authors and 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. Department of Medicine, Biochemistry and Physiology, Howard Hughes Medical Institute, 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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  1. Richard A. F. Dixon
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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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  • DOI: https://doi.org/10.1038/321075a0

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