G Protein-Coupled Receptors: Structural Basis of Selective Signaling

  • Elliott M. Ross
Part of the NATO ASI Series book series (volume 52)


Animal cells must respond appropriately to multiple hormonal signals. These signals, which may be mutually potentiative or antagonistic, must be integrated to yield appropriate intracellular signals in the form of second messengers, such as cyclic AMP, inositol phosphates, Ca2+, etc. Although receptors are responsible for detecting extracellular signals, signal integration and sorting frequently depend on the activities of GTP-binding transducer proteins known as G proteins.


Adrenergic Receptor Intracellular Loop Cytoplasmic Loop Chimeric Receptor Wasp Venom 
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. Brandt, DR, and Ross, EM (1986) Catecholamine-stimulated GTPase cycle: Multiple sites of regulation by β-adrenergic receptor and Mg2+ studiedin reconstituted receptor-Gs vesicles. J Biol Chem 261:1656–1664PubMedGoogle Scholar
  2. Cotecchia, S, Exum, S, Caron, MG, and Lefkowitz, RJ (1990) Regions of the α1-adrenergic receptor involved in coupling to phosphatidylinositol hydrolysis and enhanced sensitivity of biological function. Proc Natl Acad Sci USA 87:2896–2900PubMedCrossRefGoogle Scholar
  3. Dixon, RAF, Sigal, IS, Candelore, MR, Register, RB, Scattergood, W, Rands, E, and Strader, CD (1987) Structural features required for ligand binding to the β-adrenergic receptor. EMBO J 6:3269–3275PubMedGoogle Scholar
  4. Dixon, RAF, Sigal, IS, Rands, E, Register, RB, Candelore, MR, Blake, AD, and Strader, CD (1987) Ligand binding to the β-adrenergic receptor involves its rhodopsin-like core. Nature 326:73–77PubMedCrossRefGoogle Scholar
  5. Findlay, JBC, and Pappin, DJC (1986) The opsin family of proteins. Biochem J 238:625–642PubMedGoogle Scholar
  6. Fong, HKW, Amatruda, I, TT, Birren, BW, and Simon, MI (1987) Distinct forms of the β subunit of GTP-binding regulatory proteins identified by molecular cloning. Proc Natl Acad Sci USA 84:3792–3796PubMedCrossRefGoogle Scholar
  7. Franke, RR, Sakmar, TP, Oprian, DD, and Khorana, HG (1988) A single amino acid substitution in rhodopsin (Lysine 248 Leucine) prevents activation of transducin. J Biol Chem 263:2119–2122PubMedGoogle Scholar
  8. Gilman, AG (1987) G proteins: Transducers of receptor-generated signals. Ann Rev Biochem 56:615–649PubMedCrossRefGoogle Scholar
  9. Higashijima, T, Burnier, J, and Ross, EM (1990) Regulation of Gi and Go by mastoparan, related amphiphilic peptides and hydrophobic amines: mechanism and structural determinants of activity. J Biol Chem 265:14176–14186.PubMedGoogle Scholar
  10. Higashijima, T, Uzu, S, Nakajima, T, and Ross, EM (1988) Mastoparan, a peptide toxin from wasp venom, mimics receptors by activating GTP-binding regulatory proteins (G proteins). J Biol Chem 263:6491–6494PubMedGoogle Scholar
  11. Higashijima, T, Wakamatsu, K, Takemitsu, M, Fujino, M, Nakajima, T, and Miyazawa, T (1983) Conformational change of mastoparan from wasp venom on binding with phospholipid membrane. FEBS Lett 152:227–230PubMedCrossRefGoogle Scholar
  12. Hirai, Y, Yasuhara, T, Yoshida, H, Nakajima, T, Fujino, M, and Kitada, C (1979) A new mast cell degranulating peptide “Mastoparan” in the venom of Vespula lewisii. Chem Pharm Bull 27:1942–1944PubMedGoogle Scholar
  13. Jurnak, F (1985) Structure of the GDP domain of EF-Tu and location of the amino acids homologous to ras oncogene proteins. Science 230:32–36PubMedCrossRefGoogle Scholar
  14. Kobilka, BK, Kobilka, TS, Daniel, K, Regan, JW, Caron, MG, and Lefkowitz, RJ (1988) Chimeric α2-, β 2-adrenergic receptors: Delineation of domains involved in effector coupling and ligand binding specificity. Science 240:1310–1316PubMedCrossRefGoogle Scholar
  15. Kubo, T, Bujo, H, Akiba, I, Nakai, J, Mishina, M, and Numa, S (1988) Location of a region of the muscarinic acetylcholine receptor involved in selective effector coupling. FEBS Lett 241:119–125PubMedCrossRefGoogle Scholar
  16. Lochrie, MA, and Simon, MI (1988) G protein multiplicity in eukaryotic signal transduction systems. Biochemistry 27:4957–4965PubMedCrossRefGoogle Scholar
  17. O’Dowd, BF, Hnatowich, M, Regan, JW, Leader, WM, Caron, MG, and Lefkowitz, RJ (1988) Site-directed mutagenesis of the cytoplasmic domains of the human β 2-adrenergic receptor. J Biol Chem 263:15985–15992PubMedGoogle Scholar
  18. Okajima, F, Katada, T, and Ui, M (1985) Coupling of the guanine nucleotide regulatory protein to chemotactic peptide receptors in neutrophil membranes and its uncoupling by islet-activating protein, pertussis toxin. J Biol Chem 260:6761–6768PubMedGoogle Scholar
  19. Pai, EF, Kabsch, W, Krengel, U, Holmes, KC, John, J, and Wittinghofer, A (1989) Structure of the guanine-nucleotide-binding domain of the Ha-ras oncogene product p21 in the triphosphate conformation. Nature 341:209–214PubMedCrossRefGoogle Scholar
  20. Parker, EM, and Ross, EM (1990) G protein-coupled receptors: Structure and function of signal transducing proteins. In: Current Topics in Membranes and Transport, v 36, T Claudio, Ed, Academic Press, NY pp 131–144Google Scholar
  21. Ross, EM (1989) Signal sorting and amplification through G protein-coupled receptors. Neuron 3:141–152PubMedCrossRefGoogle Scholar
  22. Rubenstein, RC, Wong, SK-F, and Ross, EM (1987) The hydrophobic tryptic core of the β-adrenergic receptor retains Gs-regulatory activity in response to agonists and thiols. J Biol Chem 262:16655–16662PubMedGoogle Scholar
  23. Strader, CD, Sigal, IS, and Dixon, RAF (1989) Structural basis of β-adrenergic receptor function. FASEB J 3:1825–1832PubMedGoogle Scholar
  24. Strathmann, M, Wilkie, TM, and Simon, MI (1989) Diversity of the G-protein family: Sequences from five additional α subunits in the mouse. Proc Natl Acad Sci USA 86:7407–7409PubMedCrossRefGoogle Scholar
  25. Van Dop, C, Yamanaka, G, Steinberg, F, Sekura, R, Manclark, CR, Stryer, L, and Bourne, HR (1984) ADP-ribosylation of transducin by pertussis toxin blocks the light-stimulated hydrolysis of GTP and cGMP in retinal photoreceptors. J Biol Chem 259:23–25PubMedGoogle Scholar
  26. Wakamatsu, K, Higashijima, T, Fujino, M, Nakajima, T, and Miyazawa, T (1983) Transferred NOE analyses of conformations of peptides as bound to membrane bilayer of phospholipid; mastoparan X. FEBS Lett 162:123–126CrossRefGoogle Scholar
  27. Wong, SK-F, Parker, EM, and Ross, EM (1990) Chimeric muscarinic cholinergic: β-adrenergic receptors that activate Gs in response to muscarinic agonists. J Biol Chem 265: 6219–6224PubMedGoogle Scholar
  28. Wong, SK-F, Slaughter, C, Ruoho, AE, and Ross, EM (1988) The catecholamine binding site of the β-adrenergic receptor is formed by juxtaposed membrane-spanning domains. J Biol Chem 263:7925–7928PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • Elliott M. Ross
    • 1
  1. 1.Department of Pharmacology Southwestern Graduate School of Biomedical ScienceUniversity of Texas Southwestern Medical CenterDallasUSA

Personalised recommendations