A perspective on more effective GPCR-targeted drug discovery efforts

Bibliography

• Bockaert J, Dumuis A, Fagni L, et al. GPCR-GIP networks: a first step in the discovery of new therapeutic drugs? Curr Opin Drug Discov Dev 2004;7:649-57
   PubMed Web of Science ®Google Scholar
• Eglen R, Bosse R, Reisine T. Emerging concepts of guanine nucleotide-binding protein-coupled receptor (GPCR) function and implications for high-throughput screening. Assay Drug Dev Technol 2007;5:425-51
   PubMed Web of Science ®Google Scholar
• Palczewski K, Kumasaka T, Hori T, et al. Crystal structure of rhodopsin: a G protein-coupled receptor. Science 2000;289:739-45
   PubMed Web of Science ®Google Scholar
• Rosenbaum D, Cherezov V, Hanson M, et al. GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function. Science 2007;318:1266-73
   PubMed Web of Science ®Google Scholar
• Cherezov V, Rosenbaum D, Hanson M, et al. High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science 2007;318:1258-65
   PubMed Web of Science ®Google Scholar
• Rasmussen S, Choi H, Rosenbaum D, et al. Crystal structure of the human beta2 adrenergic G protein-coupled receptor. Nature 2007;450:383-7
   PubMed Web of Science ®Google Scholar
• Yeagle P, Albert A. G protein coupled receptor structure. Biochim Biophys Acta 2007;1768:808-24
   PubMed Web of Science ®Google Scholar
• Werner K, Richter C, Klein-Seetharaman J, et al. Isotope labeling of mammalian GPCRs in HEK293 cells and characterization of the C-terminus of bovine rhodopsin by high resolution liquid NMR spectroscopy. J Biomol NMR 2008;40:49-53
   Google Scholar
• Martinelli A, Tuccinardi T. Molecular modeling of adenosine receptors: new results and trends. Med Res Rev 2008;28:247-77
   PubMed Web of Science ®Google Scholar
• Heo J, Han S, Vaidehi N, et al. Prediction of the 3D structure of FMRF-amide neuropeptides bound to the mouse MrgC11 GPCR and experimental validation. Chembiochem 2007;8:1527-39
   PubMed Web of Science ®Google Scholar
• Cavasotto C, Orry A, Murgolo N, et al. Discovery of novel chemotypes to a G protein-coupled receptor through ligand-steered homology modeling and structure-based virtual screening. J Med Chem 2008;51:581-8
   PubMed Web of Science ®Google Scholar
• Sun Y, Huang J, Xiang Y, et al. Dosage-dependent switch from G protein-coupled to G protein-independent signaling by a GPCR. EMBO J 2007;26:53-64
   PubMed Web of Science ®Google Scholar
• Charest P, Oligny-Longpre G, Bonin H, et al. The V2 vasopressin receptor stimulates ERK1/2 activity independently of heterotrimeric G protein signaling. Cell Signal 2007;19:32-41
   PubMed Web of Science ®Google Scholar
• Blumer J, Smrcka A, Lanier S. Mechanistic pathways and biological roles for receptor-independent activators of G protein signaling. Pharmacol Ther 2007;113:488-506
   PubMed Web of Science ®Google Scholar
• Pyne N, Waters C, Moughal N, et al. Experimental systems for studying the role of G protein-coupled receptors in receptor tyrosine kinase signal transduction. Methods Enzymol 2004;390:451-75
   PubMed Web of Science ®Google Scholar
• Delcourt N, Bockaert J, Marin P. GPCR-jacking: from a new route in RTK signaling to a new concept in GPCR activation. Trends Pharmacol Sci 2007;28:602-7
   PubMed Web of Science ®Google Scholar
• Thomas S, Bhola N, Zhang Q, et al. Cross-talk between G protein-coupled receptor and epidermal growth factor receptor signaling pathways contributes to growth and invasion of head and neck squamous cell carcinoma. Cancer Res 2006;66:11831-9
   PubMed Web of Science ®Google Scholar
• Bhola N, Grandis J. Crosstalk between G protein-coupled receptors and epidermal growth factor receptor in cancer. Front Biosci 2008;13:1857-65
   PubMed Web of Science ®Google Scholar
• Thomsen W, Frazer J, Unett D. Functional assays for screening GPCR targets. Curr Opin Biotechnol 2005;16;655-65
   PubMed Web of Science ®Google Scholar
• Kostenis E. G proteins in drug screening: from analysis of receptor-G protein specificity to manipulation of GPCR-mediated signaling pathways. Curr Pharm Des 2006;12:1703-15
   PubMed Web of Science ®Google Scholar
• Kisselev O, Gautam N. Specific interaction with rhodopsin is dependent on the gamma subunit type in a G protein. J Biol Chem 1993;268:24519-22
   PubMed Web of Science ®Google Scholar
• Kisselev O, Pronin A, Ermolaeva M, et al. Receptor-G protein coupling is established by a potential conformational switch in the beta gamma complex. Proc Natl Acad Sci USA 1995;92:9102-6
   PubMed Web of Science ®Google Scholar
• Kleuss C, Scherubl H, Hescheler J, et al. Selectivity in signal transduction determined by gamma subunits of heterotrimeric G proteins. Science 1993;259:832-4
   PubMed Web of Science ®Google Scholar
• Andreopoulos S, Li P, Warsh J. Developmental expression of G alpha o and G alpha s isoforms in PC12 cells: relationship to neurite outgrowth. Brain Res Dev Brain Res 1995;88:30-6
   PubMedGoogle Scholar
• Wilson B, Komuro M, Farquhar M. Cellular variations in heterotrimeric G protein localization and expression in rat pituitary. Endocrinology 1994;134:233-44
   PubMed Web of Science ®Google Scholar
• Hynes T, Hughes T, Berlot C. Cellular localization of GFP-tagged alpha subunits. Methods Mol Biol 2004;237:233-46
   PubMedGoogle Scholar
• Hubbard K, Hepler J. Cell signaling diversity of the Gqalpha family of heterotrimeric G proteins. Cell Signal 2006;18:135-50
   PubMed Web of Science ®Google Scholar
• Downes G, Gautam N. The G protein subunit gene families. Genomics 1999;62:544-52
   PubMed Web of Science ®Google Scholar
• Wedegaertner P, Wilson P, Bourne H. Lipid modifications of trimeric G proteins. J Biol Chem 1995;270:503-6
   PubMed Web of Science ®Google Scholar
• Escriba P, Wedegaertner P, Goni F, et al. Lipid-protein interactions in GPCR-associated signaling. Biochim Biophys Acta 2007;1768:836-52
   PubMed Web of Science ®Google Scholar
• Milligan G, Parenti M, Magee A. The dynamic role of palmitoylation in signal transduction. Trends Biochem Sci 1995;20:181-7
   PubMed Web of Science ®Google Scholar
• Barclay E, O'Reilly M, Milligan G. Activation of an alpha2A-adrenoceptor-Galphao1 fusion protein dynamically regulates the palmitoylation status of the G protein but not of the receptor. Biochem J 2005;385:197-206
   PubMed Web of Science ®Google Scholar
• Wells C, Dingus J, Hildebrandt J. Role of the chaperonin CCT/TRiC complex in G protein betagamma-dimer assembly. J Biol Chem 2006;281:20221-32
   PubMed Web of Science ®Google Scholar
• Clapham D, Neer E. G protein beta gamma subunits. Ann Rev Pharmacol Toxicol 1997;37:167-203
   PubMed Web of Science ®Google Scholar
• Tang W, Tu Y, Nayak S, et al. Gbetagamma inhibits Galpha GTPase-activating proteins by inhibition of Galpha-GTP binding during stimulation by receptor. J Biol Chem 2006;281:4746-53
   PubMed Web of Science ®Google Scholar
• Kisselev O, Ermolaeva M, Gautam N. A farnesilated domain in the G protein gamma subunit is a specific determinant of receptor coupling. J Biol Chem 1994;269:21399-402
   PubMed Web of Science ®Google Scholar
• Sprang S. G protein mechanisms: insights from structural analysis. Ann Rev Biochem 1997;66:639-78
   PubMed Web of Science ®Google Scholar
• Bunemann M, Frank M, Lohse M. Gi protein activation in intact cells involves subunit rearrangement rather than dissociation. Proc Natl Acad Sci USA 2003;100:16077-82
   PubMed Web of Science ®Google Scholar
• Frank M, Thumer L, Lohse M, et al. G Protein activation without subunit dissociation depends on a G{alpha}(i)-specific region. J Biol Chem 2005;280:24584-90
   PubMed Web of Science ®Google Scholar
• Birnbaumer L. Expansion of signal transduction by G proteins. The second 15 years or so: from 3 to 16 alpha subunits plus betagamma dimers. Biochim Biophys Acta 2007;1768:772-93
   PubMed Web of Science ®Google Scholar
• Cabrera-Vera T, Vanhauwe J, Thomas T, et al. Insights into G protein structure, function, and regulation. Endocr Rev 2003;24:765-81
   PubMed Web of Science ®Google Scholar
• Neubig R, Connolly M, Remmers A. Rapid kinetics of G protein subunit association: a rate-limiting conformational change? FEBS Lett 1994;355:251-3
   PubMed Web of Science ®Google Scholar
• Muradov K, Artemyev N. Coupling between the N- and C-terminal domains influences transducin-alpha intrinsic GDP/GTP exchange. Biochemistry 2000;39:3937-42
   PubMed Web of Science ®Google Scholar
• Thomas T, Bae H, Medkova M, et al. An intramolecular contact in Galpha transducin that participates in maintaining its intrinsic GDP release rate. Mol Cell Biol Res Commun 2001;4:282-91
   PubMedGoogle Scholar
• Arshavsky V, Dumke C, Zhu Y, et al. Regulation of transducin GTPase activity in bovine rod outer segments. J Biol Chem 1994;269:19882-7
   PubMed Web of Science ®Google Scholar
• Tesmer J, Berman D, Gilman A, et al. Structure of RGS4 bound to AlF4-activated G(i alpha1): stabilization of the transition state for GTP hydrolysis. Cell Signal 1997;89:251-61
   Google Scholar
• Willars G. Mammalian RGS proteins: multifunctional regulators of cellular signaling. Semin Cell Dev Biol 2006;17:363-76
   PubMed Web of Science ®Google Scholar
• Tinker A. The selective interactions and functions of regulators of G protein signaling. Semin Cell Dev Biol 2006;17:377-82
   PubMed Web of Science ®Google Scholar
• Jean-Baptiste G, Yang Z, Greenwood M. Regulatory mechanisms involved in modulating RGS function. Cell Mol Life Sci 2006;63:1969-85
   PubMed Web of Science ®Google Scholar
• Tobin A. G protein-coupled receptor phosphorylation: where, when and by whom. Br J Pharmacol 2008 [Epub ahead of date]
   Google Scholar
• Lefkowitz R, Rajagopal K, Whalen E. New roles for beta-arrestins in cell signaling: not just for seven-transmembrane receptors. Mol Cell 2006;24:643-52
   PubMed Web of Science ®Google Scholar
• Engstrom M, Savola J, Wurster S. Differential efficacies of somatostatin receptor agonists for G protein activation and desensitization of somatostatin receptor subtype 4-mediated responses. J Pharmacol Exp Ther 2006;316:1262-8
   PubMed Web of Science ®Google Scholar
• Keith D, Murray S, Zaki P, et al. Morphine activates opioid receptors without causing their rapid internalization. J Biol Chem 1996;271:19021-4
   PubMed Web of Science ®Google Scholar
• Blake A, Bot G, Freeman J, et al. Differential opioid agonist regulation of the mouse mu opioid receptor. J Biol Chem 1997;272:782-90
   PubMed Web of Science ®Google Scholar
• Roettger B, Ghanekar D, Rao R, et al. Antagonist-stimulated internalization of the G protein-coupled cholecystokinin receptor. Mol Pharmacol 1997;51:357-62
   PubMed Web of Science ®Google Scholar
• Yu Y, Zhang L, Yin X, et al. Mu opioid receptor phosphorylation, desensitization, and ligand efficacy. J Biol Chem 1997;272:28869-74
   PubMed Web of Science ®Google Scholar
• Mhaouty-Kodja S, Barak L, Scheer A, et al. Constitutively active alpha-1b adrenergic receptor mutants display different phosphorylation and internalization features. Mol Pharmacol 1999;55:339-47
   PubMed Web of Science ®Google Scholar
• Lembo P, Ghahremani M, Albert P. Receptor selectivity of the cloned opossum G protein-coupled receptor kinase 2 (GRK2) in intact opossum kidney cells: role in desensitization of endogenous alpha2C-adrenergic but not serotonin 1B receptors. Mol Endocrinol 1999;13:138-47
   PubMed Web of Science ®Google Scholar
• Reiter E, Marion S, Robert F, et al. Kinase-inactive G protein-coupled receptor kinases are able to attenuate follicle-stimulating hormone-induced signaling. Biochem Biophys Res Commun 2001;282:71-8
   PubMed Web of Science ®Google Scholar
• Dhami G, Anborgh P, Dale L, et al. Phosphorylation-independent regulation of metabotropic glutamate receptor signaling by G protein-coupled receptor kinase 2. J Biol Chem 2002;277:25266-72
   PubMed Web of Science ®Google Scholar
• Perroy J, Adam L, Qanbar R, et al. Phosphorylation-independent desensitization of GABA(B) receptor by GRK4. EMBO J 2003;22:3816-24
   PubMed Web of Science ®Google Scholar
• Moore C, Milano S, Benovic J. Regulation of receptor trafficking by GRKs and arrestins. Ann Rev Physiol 2007;69:451-82
   PubMed Web of Science ®Google Scholar
• Binda A, Kabbani N, Lin R, et al. D2 and D3 dopamine receptor cell surface localization mediated by interaction with protein 4.1N. Mol Pharmacol 2002;62:507-13
   PubMed Web of Science ®Google Scholar
• Weber B, Schaper C, Scholz J, et al. Interaction of the amyloid precursor like protein 1 with the alpha2A-adrenergic receptor increases agonist-mediated inhibition of adenylyl cyclase. Cell Signal 2006;18:1748-57
   PubMed Web of Science ®Google Scholar
• Cui T, Nakagami H, Iwai M, et al. ATRAP, novel AT1 receptor associated protein, enhances internalization of AT1 receptor and inhibits vascular smooth muscle cell growth. Biochem Biophys Res Commun 2000;279:938-41
   PubMed Web of Science ®Google Scholar
• Lezcano N, Mrzljak L, Eubanks S, et al. Dual signaling regulated by calcyon, a D1 dopamine receptor interacting protein. Science 2000;287:1660-4
   PubMed Web of Science ®Google Scholar
• Binda A, Kabbani N, Levenson R. Regulation of dense core vesicle release from PC12 cells by interaction between the D2 dopamine receptor and calcium-dependent activator protein for secretion (CAPS). Biochem Pharmacol 2005;69:1451-61
   PubMed Web of Science ®Google Scholar
• Rochdi M, Laroche G, Dupre E, et al. Nm23-H2 interacts with a G protein-coupled receptor to regulate its endocytosis through an Rac1-dependent mechanism. J Biol Chem 2004;279:18981-9
   PubMed Web of Science ®Google Scholar
• Hu L, Chen W, Martin N, et al. GIPC interacts with the beta1-adrenergic receptor and regulates beta1-adrenergic receptor-mediated ERK activation. J Biol Chem 2003;278:26295-301
   PubMed Web of Science ®Google Scholar
• Lin S, Arai A, Wang Z, et al. The carboxyl terminus of the prolactin-releasing peptide receptor interacts with PDZ domain proteins involved in alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor clustering. Mol Pharmacol 2001;60:916-23
   PubMed Web of Science ®Google Scholar
• Whistler J, Enquist J, Marley A, et al. Modulation of postendocytic sorting of G protein-coupled receptors. Science 2002;297:615-20
   PubMed Web of Science ®Google Scholar
• Jeanneteau F, Diaz J, Sokoloff P, et al. Interactions of GIPC with dopamine D2, D3 but not D4 receptors define a novel mode of regulation of G protein-coupled receptors. Mol Biol Cell 2004;15:696-705
   PubMed Web of Science ®Google Scholar
• Griffon N, Jeanneteau F, Prieur F, et al. CLIC6, a member of the intracellular chloride channel family, interacts with dopamine D(2)-like receptors. Brain Res Mol Brain Res 2003;117:47-57
   PubMedGoogle Scholar
• Kabbani N, Negyessy L, Lin R, et al. Interaction with neuronal calcium sensor NCS-1 mediates desensitization of the D2 dopamine receptor. J Neurosci 2002;22:8476-86
   PubMed Web of Science ®Google Scholar
• Sneddon W, Syme C, Bisello A, et al. Activation-independent parathyroid hormone receptor internalization is regulated by NHERF1 (EBP50). J Biol Chem 2003;278:43787-96
   PubMed Web of Science ®Google Scholar
• Anborgh P, Godin C, Pampillo M, et al. Inhibition of metabotropic glutamate receptor signaling by the huntingtin-binding protein optineurin. J Biol Chem 2005;280:34840-8
   PubMed Web of Science ®Google Scholar
• Seachrist J, Laporte S, Dale L, et al. Rab5 association with the angiotensin II type 1A receptor promotes Rab5 GTP binding and vesicular fusion. J Biol Chem 2002;277:679-85
   PubMed Web of Science ®Google Scholar
• Abramow-Newerly M, Roy A, Nunn C, et al. RGS proteins have a signaling complex: interactions between RGS proteins and GPCRs, effectors, and auxiliary proteins. Cell Signal 2006;18:579-91
   PubMed Web of Science ®Google Scholar
• Bhattacharya M, Babwah A, Godin C, et al. Ral and phospholipase D2-dependent pathway for constitutive metabotropic glutamate receptor endocytosis. J Neurosci 2004;24:8752-61
   PubMed Web of Science ®Google Scholar
• Canela L, Lujan R, Lluis C, et al. The neuronal Ca(2+)-binding protein 2 (NECAB2) interacts with the adenosine A(2A) receptor and modulates the cell surface expression and function of the receptor. Mol Cell Neurosci 2007;36:1-12
   PubMed Web of Science ®Google Scholar
• He F, Qiao Z, Cai J, et al. Involvement of HSP-90 in CB2 cannabinoid receptor-mediated cell migration – a new role of HSP-90 in migration signaling of a G protein-coupled receptor. Mol Pharmacol 2007 [Epub ahead of print]
   Google Scholar
• Kabbani N, Levenson R. A proteomic approach to receptor signaling: molecular mechanisms and therapeutic implications derived from discovery of the dopamine D(2) receptor signalplex. Eur J Pharmacol 2007 [Epub ahead of print]
   PubMedGoogle Scholar
• Langmead C, Christopoulos A. Allosteric agonists of 7TM receptors: expanding the pharmacological toolbox. Trends Pharmacol Sci 2006;27:475-81
   PubMed Web of Science ®Google Scholar
• Christopoulos A, Kenakin T. G protein-coupled receptor allosterism and complexing. Pharmacol Rev 2002;54:323-74
   PubMed Web of Science ®Google Scholar
• Christopoulos A. Allosteric binding sites on cell-surface receptors: novel targets for drug discovery. Nat Rev Drug Discov 2002;1:198-210
   PubMed Web of Science ®Google Scholar
• Raddatz R, Schaffhauser H, Marino M. Allosteric approaches to the targeting of G protein-coupled receptors for novel drug discovery: a critical assessment. Biochem Pharmacol 2007;74:383-91
   PubMed Web of Science ®Google Scholar
• May L, Christopoulos A. Allosteric modulators of G protein-coupled receptors. Curr Opin Pharmacol 2003;3:551-6
   PubMed Web of Science ®Google Scholar
• Lewandowicz A, Vepsalainen J, Laitinen J. The ‘allosteric modulator’ SCH-202676 disrupts G protein-coupled receptor function via sulfhydryl-sensitive mechanisms. Br J Pharmacol 2006;147:422-9
   PubMed Web of Science ®Google Scholar
• Jakubik J, Bacakova L, Lisa V, et al. Activation of muscarinic acetylcholine receptors via their allosteric binding sites. Proc Natl Acad Sci USA 1996;93:8705-9
   PubMed Web of Science ®Google Scholar
• Thomas E, Carson M, Neal M, et al. Unique allosteric regulation of 5-hydroxytryptamine receptor-mediated signal transduction by oleamide. Proc Natl Acad Sci USA 1997;94:14115-9
   PubMed Web of Science ®Google Scholar
• Kinney G, O'Brien J, Lemaire W, et al. A novel selective positive allosteric modulator of metabotropic glutamate receptor subtype 5 has in vivo activity and antipsychotic-like effects in rat behavioral models. J Pharmacol Exp Ther 2005;313:199-206
   PubMed Web of Science ®Google Scholar
• Holst B, Elling C, Schwartz T. Metal ion-mediated agonism and agonist enhancement in melanocortin MC1 and MC4 receptors. J Biol Chem 2002;277:47662-70
   PubMed Web of Science ®Google Scholar
• Holst B, Brandt E, Bach A, et al. Nonpeptide and peptide growth hormone secretagogues act both as ghrelin receptor agonist and as positive or negative allosteric modulators of ghrelin signaling. Mol Endocrinol 2005;19:2400-11
   PubMed Web of Science ®Google Scholar
• Binet V, Brajon C, Le Corre L, et al. The heptahelical domain of GABA(B2) is activated directly by CGP7930, a positive allosteric modulator of the GABA(B) receptor. J Biol Chem 2004;279:29085-91
   PubMed Web of Science ®Google Scholar
• Knudsen L, Kiel D, Teng M, et al. Small-molecule agonists for the glucagon-like peptide 1 receptor. Proc Natl Acad Sci USA 2007;104:937-42
   PubMed Web of Science ®Google Scholar
• Schwartz T, Holst B. Ago-allosteric modulation and other types of allostery in dimeric 7TM receptors. J Recept Signal Transduct Res 2006;26:107-28
   PubMed Web of Science ®Google Scholar
• Gbahou F, Rouleau A, Morisset S, et al. Protean agonism at histamine H3 receptors in vitro and in vivo. Proc Natl Acad Sci USA 2003;100:11086-91
   PubMed Web of Science ®Google Scholar
• Milligan G. Principles: extending the utility of [35S]GTP gamma S binding assays. Trends Pharmacol Sci 2003;24:87-90
   PubMed Web of Science ®Google Scholar
• Alberts G, Pregenzer J, Im W. Advantages of heterologous expression of human D2long dopamine receptors in human neuroblastoma SH-SY5Y over human embryonic kidney 293 cells. Br J Pharmacol 2000;131:514-20
   PubMed Web of Science ®Google Scholar
• Molinari P, Casella I, Costa T. Functional complementation of high-efficiency resonance energy transfer: a new tool for the study of protein binding interactions in living cells. Biochem J 2008;409:251-61
   PubMed Web of Science ®Google Scholar
• Galés C, Rebois R, Hogue M, et al. Real-time monitoring of receptor and G protein interactions in living cells. Nat Methods 2005;2:177-84
   PubMed Web of Science ®Google Scholar
• Nobles M, Benians A, Tinker A. Heterotrimeric G proteins precouple with G protein-coupled receptors in living cells. Proc Natl Acad Sci USA 2005;102:18706-11
   PubMed Web of Science ®Google Scholar
• Lohse M, Hoffmann C, Nikolaev V, et al. Kinetic analysis of G protein-coupled receptor signaling using fluorescence resonance energy transfer in living cells. Adv Protein Chem 2007;74:167-88
   PubMedGoogle Scholar
• Briddon S, Hill S. Pharmacology under the microscope: the use of fluorescence correlation spectroscopy to determine the properties of ligand-receptor complexes. Trends Pharmacol Sci 2007;28:637-45
   PubMed Web of Science ®Google Scholar
• De Lean A, Stadel J, Lefkowitz R. A ternary complex model explains the agonist-specific binding properties of the adenylyl cyclase-coupled beta-adrenergic receptor. J Biol Chem 1980;255:7108-17
   PubMed Web of Science ®Google Scholar
• Harrison C, Traynor J. The [35S]GTPgammaS binding assay: approaches and applications in pharmacology. Life Sci 2003;74:489-508
   PubMed Web of Science ®Google Scholar
• DeLapp N. The antibody-capture [(35)S]GTPgammaS scintillation proximity assay: a powerful emerging technique for analysis of GPCR pharmacology. Trends Pharmacol Sci 2004;25:400-1
   PubMed Web of Science ®Google Scholar
• Bertin B, Freissmuth M, Jockers R, et al. Cellular signaling by an agonist-activated receptor/Gs alpha fusion protein. Proc Natl Acad Sci USA 1994;91:8827-31
   PubMed Web of Science ®Google Scholar
• Milligan G, Parenty G, Stoddart L, et al. Novel pharmacological applications of G protein-coupled receptor-G protein fusions. Curr Opin Pharmacol 2007 [Epub ahead of print]
   PubMedGoogle Scholar
• Molinari P, Ambrosio C, Riitano D, et al. Promiscuous coupling at receptor-Galpha fusion proteins. The receptor of one covalent complex interacts with the alpha-subunit of another. J Biol Chem 2003;278:15778-88
   PubMed Web of Science ®Google Scholar
• Suga H, Haga T. Ligand screening system using fusion proteins of G protein-coupled receptors with G protein alpha subunits. Neurochem Int 2007;51:140-64
   PubMed Web of Science ®Google Scholar
• Van Dop C, Yamanaka G, Steinberg F, et al. ADP-ribosylation of transducin by pertussis toxin blocks the light-stimulated hydrolysis of GTP and cGMP in retinal photoreceptors. J Biol Chem 1984;259:23-6
   PubMed Web of Science ®Google Scholar
• Umemori H, Inoue T, Kume S, et al. Activation of the G protein Gq/11 through tyrosine phosphorylation of the alpha subunit. Science 1997;276:1878-81
   PubMed Web of Science ®Google Scholar
• McFadzean I, Caulfield M, Vallis Y, et al. Injection of antisera into cells to study G protein regulation of channel function. Methods Enzymol 1994;238:357-64
   PubMed Web of Science ®Google Scholar
• Hamm HE, Deretic D, Arendt A, et al. Site of G protein binding to rhodopson mapped with synthetic peptides from the α subunit. Science 1988;241:832-5
   PubMed Web of Science ®Google Scholar
• Rasenick M, Watanabe M, Lazarevic M, et al. Synthetic peptides as probes for G protein function. Carboxyl-terminal G alpha s peptides mimic Gs and evoke high affinity agonist binding to beta-adrenergic receptors. J Biol Chem 1994;269:21519-25
   PubMed Web of Science ®Google Scholar
• Gilchrist A, Mazzoni M, Dineen B, et al. Antagonists of the receptor-G protein interface block Gi-coupled signal transduction. J Biol Chem 1998;273:14912-9
   PubMed Web of Science ®Google Scholar
• D'Ursi A, Giusti L, Albrizio S, et al. A membrane-permeable peptide containing the last 21 residues of the G alpha(s) carboxyl terminus inhibits G(s)-coupled receptor signaling in intact cells: correlations between peptide structure and biological activity. Mol Pharmacol 2006;69:727-36
   PubMed Web of Science ®Google Scholar
• Conklin B, Farfel Z, Lustig K, et al. Substitution of three amino acids switches receptor specificity of Gq alpha to that of Gi alpha. Nature 1993;363:274-6
   PubMed Web of Science ®Google Scholar
• Kostenis E, Conklin B, Wess J. Molecular basis of receptor/G protein coupling selectivity studied by coexpression of wild type and mutant m2 muscarinic receptors with mutant G alpha(q) subunits. Biochemistry 1997;36:1487-95
   PubMed Web of Science ®Google Scholar
• Blahos Jn, Mary S, Perroy J, et al. Extreme C terminus of G protein α-subunits contains a site that discriminates between Gi-coupled metabotropic glutamate receptors. J Biol Chem 1998;273:25765-9
   PubMed Web of Science ®Google Scholar
• Conklin B, Herzmark P, Ishida S, et al. Carboxyl-terminal mutations of Gq alpha and Gs alpha that alter the fidelity of receptor activation. Mol Pharmacol 1996;50:885-90
   PubMed Web of Science ®Google Scholar
• Gilchrist A, Bunemann M, Li A, et al. A dominant-negative strategy for studying roles of G proteins in vivo. J Biol Chem 1999;274:6610-6
   PubMed Web of Science ®Google Scholar
• Gilchrist A, Vanhauwe J, Li A, et al. G alpha minigenes expressing C-terminal peptides serve as specific inhibitors of thrombin-mediated endothelial activation. J Biol Chem 2001;276:25672-9
   PubMed Web of Science ®Google Scholar
• Gilchrist A, Li A, Hamm H. G alpha COOH-terminal minigene vectors dissect heterotrimeric G protein signaling. Sci STKE 2002;5:PL1
   Google Scholar
• Lin F, Sepich D, Chen S, et al. Essential roles of G{alpha}12/13 signaling in distinct cell behaviors driving zebrafish convergence and extension gastrulation movements. J Cell Biol 2005;169:777-87
   PubMed Web of Science ®Google Scholar
• Singh A, Gilchrist A, Voyno-Yasenetskaya T, et al. G alpha12/G alpha13 subunits of heterotrimeric G proteins mediate parathyroid hormone activation of phospholipase D in UMR-106 osteoblastic cells. Endocrinology 2005;146:2171-5
   PubMed Web of Science ®Google Scholar
• Lee C, Rivera R, Dubin A, et al. LPA(4)/GPR23 is a lysophosphatidic acid (LPA) receptor utilizing G(s)-, G(q)/G(i)-mediated calcium signaling and G(12/13)-mediated Rho activation. J Biol Chem 2007;282:4310-7
   PubMed Web of Science ®Google Scholar
• Coffield V, Helms W, Jiang Q, et al. Galpha13 mediates a signal that is essential for proliferation and survival of thymocyte progenitors. J Exp Med 2004;200:1315-24
   PubMed Web of Science ®Google Scholar
• Coward P, Chan S, Wada H, et al. Chimeric G proteins allow a high-throughput signaling assay of Gi-coupled receptors. Anal Biochem 1999;270:242-8
   PubMed Web of Science ®Google Scholar
• Xing H, Tran H, Knapp T, et al. A fluorescent reporter assay for the detection of ligands acting through Gi protein-coupled receptors. J Recept Signal Transduct Res 2000;20:189-210
   PubMed Web of Science ®Google Scholar
• Kowal D, Nawoschik S, Ochalski R, et al. Functional calcium coupling with the human metabotropic glutamate receptor subtypes 2 and 4 by stable co-expression with a calcium pathway facilitating G protein chimera in Chinese hamster ovary cells. Biochem Pharmacol 2003;66:785-90
   PubMed Web of Science ®Google Scholar
• Gopalakrishnan S, Moreland R, Kofron J, et al. A cell-based microarrayed compound screening format for identifying agonists of G protein-coupled receptors. Anal Biochem 2003;321:192-201
   PubMed Web of Science ®Google Scholar
• New D, Wong Y. Characterization of CHO cells stably expressing a G alpha 16/z chimera for high-throughput screening of GPCRs. Assay Drug Dev Technol 2004;2:269-80
   PubMed Web of Science ®Google Scholar
• Hazari A, Lowes V, Chan J, et al. Replacement of the alpha5 helix of Galpha16 with Galphas-specific sequences enhances promiscuity of Galpha16 toward Gs-coupled receptors. Cell Signal 2004;16:51-62
   PubMed Web of Science ®Google Scholar
• Takeda S, Okada T, Okamura M, et al. The receptor-Galpha fusion protein as a tool for ligand screening: a model study using a nociceptin receptor-Galphai2 fusion protein. J Biochem (Tokyo) 2004;135:597-604
   PubMed Web of Science ®Google Scholar
• US Patent # 7,208,279
   Google Scholar
• Bonacci T, Mathews J, Yuan C, et al. Differential targeting of Gbetagamma-subunit signaling with small molecules. Science 2006;312:443-6
   PubMed Web of Science ®Google Scholar
• Mayer G, Wulffen B, Huber C, et al. An RNA molecule that specifically inhibits G protein-coupled receptor kinase 2 in vitro. RNA 2008 [Epub ahead of print]
   PubMedGoogle Scholar
• Roman D, Talbot J, Roof R, et al. Identification of small-molecule inhibitors of RGS4 using a high-throughput flow cytometry protein interaction assay. Mol Pharmacol 2007;71:169-75
   PubMed Web of Science ®Google Scholar
• Galandrin S, Bouvier M. Distinct signaling profiles of beta1 and beta2 adrenergic receptor ligands toward adenylyl cyclase and mitogen-activated protein kinase reveals the pluridimensionality of efficacy. Mol Pharmacol 2006;70:1575-84
   PubMed Web of Science ®Google Scholar
• Krumins A, Barber R. Examination of the effects of increasing Gs protein on beta2-adrenergic receptor, Gs, and adenylyl cyclase interactions. Biochem Pharmacol 1997;54:61-72
   PubMed Web of Science ®Google Scholar
• Waelbroeck M. Activation of guanosine 5′-[gamma-(35)S]thio-triphosphate binding through M(1) muscarinic receptors in transfected Chinese hamster ovary cell membranes; 1. Mathematical analysis of catalytic G protein activation. Mol Pharmacol 2001;59:875-85
   PubMed Web of Science ®Google Scholar
• Hermans E. Biochemical and pharmacological control of the multiplicity of coupling at G protein-coupled receptors. Pharmacol Ther 2003;99:25-44
   PubMed Web of Science ®Google Scholar
• Berg K, Maayani S, Goldfarb J, et al. Effector pathway-dependent relative efficacy at serotonin type 2A and 2C receptors: evidence for agonist-directed trafficking of receptor stimulus. Mol Pharmacol 1998;54:94-104
   PubMed Web of Science ®Google Scholar
• Jarpe M, Knall C, Mitchell F, et al. [D-Arg1,D-Phe5,D-Trp7,9,Leu11]Substance P acts as a biased agonist toward neuropeptide and chemokine receptors. J Biol Chem 1998;273:3097-104
   PubMed Web of Science ®Google Scholar
• Perez D, Karnik S. Multiple signaling states of G protein-coupled receptors. Pharmacol Rev 2005;57:147-61
   PubMed Web of Science ®Google Scholar
• Pineyro G, Archer-Lahlou E. Ligand-specific receptor states: implications for opiate receptor signaling and regulation. Cell Signal 2007;19:8-19
   PubMed Web of Science ®Google Scholar
• Kobilka B, Deupi X. Conformational complexity of G protein-coupled receptors. Trends Pharmacol Sci 2007;28:397-406
   PubMed Web of Science ®Google Scholar
• Kenakin T. Predicting therapeutic value in the lead optimization phase of drug discovery. Nat Rev Drug Discov 2003;2:429-38
   PubMed Web of Science ®Google Scholar
• Tilley D, Rockman H. Role of beta-adrenergic receptor signaling and desensitization in heart failure: new concepts and prospects for treatment. Expert Rev Cardiovasc Ther 2006;4:417-32
   PubMedGoogle Scholar
• Xiao R, Zhang S, Chakir K, et al. Enhanced G(i) signaling selectively negates beta2-adrenergic receptor (AR)-but not beta1-AR-mediated positive inotropic effect in myocytes from failing rat hearts. Circulation 2003;108:1633-9
   PubMed Web of Science ®Google Scholar
• Baker J, Hall I, Hill S. Agonist and inverse agonist actions of beta-blockers at the human beta 2-adrenoceptor provide evidence for agonist-directed signaling. Mol Pharmacol 2003;64:1357-69
   PubMed Web of Science ®Google Scholar
• Ponicke K, Groner F, Heinroth-Hoffmann I, et al. Agonist-specific activation of the beta2-adrenoceptor/Gs-protein and beta2-adrenoceptor/Gi-protein pathway in adult rat ventricular cardiomyocytes. Br J Pharmacol 2006;147:714-9
   PubMed Web of Science ®Google Scholar
• Mazzuco T, Chabre O, Feige J, et al. Aberrant GPCR expression is a sufficient genetic event to trigger adrenocortical tumorigenesis. Mol Cell Endocrinol 2007;265-266:23-8
   PubMed Web of Science ®Google Scholar
• Li S, Huang S, Peng S. Overexpression of G protein-coupled receptors in cancer cells: involvement in tumor progression. Int J Oncol 2005;27:1329-39
   PubMed Web of Science ®Google Scholar
• Arora P, Ricks T, Trejo J. Protease-activated receptor signaling, endocytic sorting and dysregulation in cancer. J Cell Sci 2007;120:921-8
   PubMed Web of Science ®Google Scholar
• Wang P, DeFea K. Protease-activated receptor-2 simultaneously directs beta-arrestin-1-dependent inhibition and Galphaq-dependent activation of phosphatidylinositol 3-kinase. Biochemistry 2006;45:9374-85
   PubMed Web of Science ®Google Scholar
• Eglen R. Emerging concepts in GPCR function-the influence of cell phenotype on GPCR pharmacology. Proc West Pharmacol Soc 2005;48:31-4
   PubMedGoogle Scholar
• Nelson C, Challiss R. ‘Phenotypic’ pharmacology: the influence of cellular environment on G protein-coupled receptor antagonist and inverse agonist pharmacology. Biochem Pharmacol 2007;73:737-51
   PubMed Web of Science ®Google Scholar
• Torrecilla I, Spragg E, Poulin B, et al. Phosphorylation and regulation of a G protein-coupled receptor by protein kinase CK2. J Cell Biol 2007;177:127-37
   PubMed Web of Science ®Google Scholar
• Kenakin T. Differences between natural and recombinant G protein-coupled receptor systems with varying receptor/G protein stoichiometry. Trends Pharmacol Sci 1997;18:456-64
   PubMed Web of Science ®Google Scholar
• Gonzalez-Maeso J, Rodriguez-Puertas R, Meana J. Quantitative stoichiometry of G proteins activated by mu-opioid receptors in postmortem human brain. Eur J Pharmacol 2002;452:21-33
   PubMed Web of Science ®Google Scholar
• Ernst O, Gramse V, Kolbe M, et al. Monomeric G protein-coupled receptor rhodopsin in solution activates its G protein transducin at the diffusion limit. Proc Natl Acad Sci USA 2007;104:10859-64
   PubMed Web of Science ®Google Scholar
• Philip F, Sengupta P, Scarlata S. Signaling through a G protein-coupled receptor and its corresponding G protein follows a stoichiometrically limited model. J Biol Chem 2007;282:19203-16
   PubMed Web of Science ®Google Scholar
• Zaworski P, Alberts G, Pregenzer J, et al. Efficient functional coupling of the human D3 dopamine receptor to G(o) subtype of G proteins in SH-SY5Y cells. Br J Pharmacol 1999;128:1181-8
   PubMed Web of Science ®Google Scholar
• Chidiac P, Nouet S, Bouvier M. Agonist-induced modulation of inverse agonist efficacy at the beta 2-adrenergic receptor. Mol Pharmacol 1996;50:662-9
   PubMed Web of Science ®Google Scholar
• Pineyro G, Azzi M, deLean A, et al. Reciprocal regulation of agonist and inverse agonist signaling efficacy upon short-term treatment of the human delta-opioid receptor with an inverse agonist. Mol Pharmacol 2005;67:336-48
   PubMed Web of Science ®Google Scholar
• Lane J, Powney B, Wise A, et al. Protean agonism at the dopamine D2 receptor: (S)-3-(3-hydroxyphenyl)-N-propylpiperidine is an agonist for activation of Go1 but an antagonist/inverse agonist for Gi1,Gi2, and Gi3. Mol Pharmacol 2007;71:1349-59
   PubMed Web of Science ®Google Scholar
• Gesty-Palmer D, Chen M, Reiter E, et al. Distinct beta-arrestin- and G protein-dependent pathways for parathyroid hormone receptor-stimulated ERK1/2 activation. J Biol Chem 2006;281:10856-64
   PubMed Web of Science ®Google Scholar
• MacKinnon A, Waters C, Jodrell D, et al. Bombesin and substance P analogs differentially regulate G protein coupling to the bombesin receptor. Direct evidence for biased agonism. J Biol Chem 2001;276:28083-91
   PubMed Web of Science ®Google Scholar
• Jorgensen R, Kubale V, Vrecl M, et al. Oxyntomodulin differentially affects glucagon-like peptide-1 receptor beta-arrestin recruitment and signaling through Galpha(s). J Pharmacol Exp Ther 2007;322:148-54
   PubMed Web of Science ®Google Scholar
• Groer C, Tidgewell K, Moyer R, et al. An opioid agonist that does not induce micro-opioid receptor-arrestin interactions or receptor internalization. Mol Pharmacol 2007;71:549-57
   PubMed Web of Science ®Google Scholar
• Wang Y, Tang K, Inan S, et al. Comparison of pharmacological activities of three distinct ligands (Salvinorin A, TRK-820 and 3FLB) on opioid receptors in vitro and their antipruritic and antinociceptive activities in vivo. J Pharmacol Exp Ther 2005;312:220-30
   PubMed Web of Science ®Google Scholar
• Aplin M, Christensen G, Schneider M, et al. The angiotensin type 1 receptor activates extracellular signal-regulated kinases 1 and 2 by G protein-dependent and -independent pathways in cardiac myocytes and langendorff-perfused hearts. Basic Clin Pharmacol Toxicol 2007;100:289-95
   PubMed Web of Science ®Google Scholar
• Jansson C, Kukkonen J, Nasman J, et al. Protean agonism at alpha2A-adrenoceptors. Mol Pharmacol 1998;53:963-8
   PubMed Web of Science ®Google Scholar
• Watson C, Chen G, Irving P, et al. The use of stimulus-biased assay systems to detect agonist-specific receptor active states: implications for the trafficking of receptor stimulus by agonists. Mol Pharmacol 2000;58:1230-8
   PubMed Web of Science ®Google Scholar
• Mukhopadhyay S, Howlett A. Chemically distinct ligands promote differential CB1 cannabinoid receptor-Gi protein interactions. Mol Pharmacol 2005;67:2016-24
   PubMed Web of Science ®Google Scholar
• Reversi A, Rimoldi V, Marrocco T, et al. The oxytocin receptor antagonist atosiban inhibits cell growth via a ‘biased agonist’ mechanism. J Biol Chem 2005;280:16311-8
   PubMed Web of Science ®Google Scholar
• Beyermann M, Heinrich N, Fechner K, et al. Achieving signaling selectivity of ligands for the corticotropin-releasing factor type 1 receptor by modifying the agonist's signaling domain. Br J Pharmacol 2007;151:851-9
   PubMed Web of Science ®Google Scholar
• Kukkonen J, Jansson C, Akerman K. Agonist trafficking of G(i/o)-mediated alpha(2A)-adrenoceptor responses in HEL 92.1.7 cells. Br J Pharmacol 2001;132:1477-84
   PubMed Web of Science ®Google Scholar
• Weber T, Markillie L. Regulation of activator protein-1 by 8-iso-prostaglandin E2 in a thromboxane A2 receptor-dependent and -independent manner. Mol Pharmacol 2003;63:1075-81
   PubMed Web of Science ®Google Scholar