Genetic Analysis of the β-Adrenergic Receptor

  • Catherine D. Strader
  • Richard A. F. Dixon
Part of the Applications of Molecular Genetics to Pharmacology book series


Many hormone and neurotransmitter receptors mediate their signals through interaction with guanine nucleotide-binding regulatory proteins (G-proteins) (see Gilman, 1987, for review). As described elsewhere in this volume, the cloning of the genes for these receptor proteins has revealed a large degree of structural homology within this family of receptors. The homology among the receptors is concentrated within the hydrophobic cores of the proteins, formed by the seven putative transmembrane helices, whereas the extracellular and intracellular hydrophilic loop regions are more divergent. Although the hormones and neurotransmitters which couple various receptors to G-protein-mediated signaling pathways represent a diverse group of small molecule and peptide ligands, there are striking parallels in their mechanisms of signal transduction. Thus, the structural similarities among G-protein-coupled receptors probably reflect similar molecular interactions which are responsible for their common mechanism of action. For this reason, the structural and functional information obtained for one of these receptor proteins should be applicable to the entire family of G-protein-coupled receptors.


Ligand Binding Site Mutant Receptor Muscarinic Acetylcholine Receptor Chimeric Receptor Antagonist Binding 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aoki C, Zemcik BA, Strader CD, Pickel VM (1989): Cytoplasmic loop of ß-adrenergic receptors: Synaptic and intracellular localization and relation to catecholaminergic neurons in the nuclei of the solitary tracts. Brain Res 493: 331–347CrossRefGoogle Scholar
  2. Cheung AH, Sigal IS, Dixon RAF, Strader CD (1989): Agonist-promoted seques-tration of the ß 2-adrenergic receptor requires regions involved in functional coupling with Gs. Mol Pharmacol 34: 132–138Google Scholar
  3. Dixon RAF, Sigal IS, Rands E, Register RB, Candelore MR, Blake AD, Strader CD (1987a): Ligand binding to the ß-adrenergic receptor involves its rhodopsin-like core. Nature 326: 73–77CrossRefGoogle Scholar
  4. Dixon RAF, Sigal IS, Candelore MR, Register RB, Scattergood W, Rands E, Strader CD (1987b): Structural features required for ligand binding to the ß-adrenergic receptor. EMBO J 6: 3269–3275Google Scholar
  5. Dixon RAF, Sigal IS, Strader CD (1989a): Structure-function analysis of the ß-adrenergic receptor. Cold Spring Harbor Symp Quant Biol 53: 487–497CrossRefGoogle Scholar
  6. Dixon RAF, Hill WS, Candelore MR, Rands E, Diehl RE, Marshall MS, Sigal IS, Strader CD (1989b): Genetic analysis of the molecular basis for ß-adrenergic receptor subtype specificity. Proteins 6: 267–274CrossRefGoogle Scholar
  7. Findlay JBC, Pappin DJC (1986): The opsin family of proteins. Biochem J 238: 625–642Google Scholar
  8. Frielle, T, Daniel, KW, Caron, MG, Lefkowitz, RJ (1988): Structural basis of ß-adrenergic receptor subtype specificity studied with chimeric ß 1 / ß2-adrenergic receptors. Proc Natl Acad Sci USA 85: 9494–9498CrossRefGoogle Scholar
  9. Gilman AG (1987): G-Proteins: Transducers of receptor-generated signals. Annu Rev Biochem 56: 615–624CrossRefGoogle Scholar
  10. Hargrave P, McDowell JH, Feldman RJ, Atkinson PH, Rao JKM, Argos P (1984): Rhodopsin’s protein and carbohydrate structure, selected aspects. Vision Res 24: 1487–1493CrossRefGoogle Scholar
  11. Kobilka BK, Kobilka TS, Daniel K, Regan JW, Caron MG, Lefkowitz RJ (1988): Chimeric α 2-,ß2adrenergic receptors: Delineation of domains involved in effector coupling and ligand binding specificity. Science 240: 1310–1316CrossRefGoogle Scholar
  12. Kubo T, Bujo H, Akiba I, Nakai J, Mishina M, Numa S (1988): Location of a region of the muscarinic acetylcholine receptor involved in selective effector coupling. FEBS Lett 241: 119–125CrossRefGoogle Scholar
  13. Main BG, Tucker H (1985): Recent advances in ß-adrenergic blocking agents. Prog Med Chem 22: 122–143Google Scholar
  14. O’Dowd BF, Hnatowich M, Regan JW, Leader WM, Caron MG, Lefkowitz RJ (1988): Site-directed mutagenesis of the cytoplasmic domains of the human ß 2-adrenergic receptor. J Biol Chem 263: 15985–15992Google Scholar
  15. Rands E, Candelore MR, Cheung AH, Strader CD, and Dixon RAF (1990): Mutational analysis of ß-adrenergic receptor glycosylation: N-Linked sugar addition is required for receptor transport, but not function. J Biol Chem 265: 10759–10764Google Scholar
  16. Strader CD, Sigal IS, Register RB, Candelore MR, Rands E, and Dixon RAF (1987a): Identification of residues required for ligand binding to the ß-adrenergic receptor. Proc Natl Acad Sci USA 84: 4384–4388CrossRefGoogle Scholar
  17. Strader CD, Dixon RAF, Cheung AH, Candelore MR, Blake AD, Sigal IS (1987b): Mutations that uncouple the ß-adrenergic receptor from Gs and increase agonist affinity. J Biol Chem 262: 16439–16443Google Scholar
  18. Strader CD, Sigal IS, Candelore MR, Rands E, Hill WS, Dixon RAF (1988): Conserved aspartic acid residues 79 and 113 of the ß-adrenergic receptor have different roles in receptor function. J Biol Chem 263: 10267–10271Google Scholar
  19. Strader CD, Sigal IS, Dixon RAF (1989a): Structural basis of ß-adrenergic receptor function. FASEB J 3: 1825–1832Google Scholar
  20. Strader CD, Candelore MR, Hill WS, Dixon RAF, Sigal IS (1989b): A single amino acid substitution in the ß-adrenergic receptor promotes partial agonist activity from antagonists. J Biol Chem 264: 16470–16477Google Scholar
  21. Strader CD, Candelore MR, Hill WS, Sigal IS, Dixon RAF (1989c): Identification of two serine residues involved in agonist activation of the ß-adrenergic receptor. J Biol Chem 264: 13572–13578Google Scholar
  22. Strader CD, Sigal IS, Dixon RAF (1989d): Genetic approaches to the determination of structure-function relationships of G-protein-coupled receptors. Trends Pharmacol Sci Suppl, 26–30Google Scholar

Copyright information

© Birkhäuser Boston 1992

Authors and Affiliations

  • Catherine D. Strader
  • Richard A. F. Dixon

There are no affiliations available

Personalised recommendations