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Nature 321, 75 - 79 (01 May 1986); doi:10.1038/321075a0

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

Richard A. F. Dixon*, Brian K. Kobilka, David J. Strader, Jeffrey L. Benovic, Henrik G. Dohlman, Thomas Frielle, Mark A. Bolanowski, Carl D. Bennett§, Elaine Rands*, Ronald E. Diehl*, Richard A. Mumford, Eve E. Slater, Irving S. Sigal*, Marc G. Caron, Robert J. Lefkowitz & Catherine D. Strader

Departments of *Virus and Cell Biology Research and §Medicinal Chemistry, Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania 19486, USA
Howard Hughes Medical Institute, Department of Medicine, Biochemistry and Physiology, Duke University Medical Center, Durham, North Carolina 27710, USA
Department of Biochemistry and Molecular Biology, Merck Sharp and Dohme Research Laboratories, Rahway, New Jersey 07065, USA

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, β 1 and β 2 receptors, stimulate adenylate cyclase on binding specific catecholamines1. Recently, the avian erythrocyte β 1, the amphibian erythrocyte β 2 and the mammalian lung β 2 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 vitro 6, 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 β 2AR. 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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