Emerging concepts of guanine nucleotide-binding protein-coupled receptor (GPCR) function and implications for high throughput screening

Assay and Drug Development Technologies

Volumn 5, Issue 3, 2007, Pages 425-451

  Eglen, Richard M ^a   Bosse, Roger ^a   Reisine, Terry ^b  

^a PERKINELMER INC   (United States)

^b PerkinElmer ^*

Author keywords

[No Author keywords available]

Indexed keywords

CALCIUM ION; CELL PROTEIN; CYCLIC AMP; GUANINE NUCLEOTIDE BINDING PROTEIN; INOSITOL PHOSPHATE; MITOGEN ACTIVATED PROTEIN KINASE; RECEPTOR ACTIVITY MODIFYING PROTEIN; RETINA S ANTIGEN;

ENZYME ACTIVATION; HIGH THROUGHPUT SCREENING; HUMAN GENOME; LIGAND BINDING; OLIGOMERIZATION; PROTEIN DOMAIN; PROTEIN MOTIF; PROTEIN PROTEIN INTERACTION; REVIEW; SECOND MESSENGER;

ANIMALS; ARRESTINS; BINDING SITES; CALCIUM; CYCLIC AMP; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; GTP-BINDING PROTEINS; HUMANS; LIGANDS; MUTATION; RECEPTORS, G-PROTEIN-COUPLED; RHODOPSIN KINASE;

EID: 34447513030     PISSN: 1540658X     EISSN: None     Source Type: Journal    
DOI: 10.1089/adt.2007.062     Document Type: Review

References (189)

1. nd ed., M. Nijhoff, Boston, 1995.
2. Wilson S, Bergsma D: Orphan G-protein coupled receptors: novel drug targets for the pharmaceutical industry. Drug Des Discov 2000;17:105-114.
3. Eglen RM: Functional G protein-coupled receptor assays for primary and secondary screening. Comb Chem High Throughput Screen 2005;8:311-318.
4. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, et al.: The sequence of the human genome. Science 2001;291:1304-1351.
5. Dohlman HG, Throner J, Caron MG, Lefkowitz R: Model systems for the study of seven-transmembrane-segment receptors. Annu Rev Biochem 1991;60:653-688.
6. Pierce KL, Premont RT, Lefkowitz RJ: Seven-transmembrane receptors. Nat Rev Mol Cell Biol 2002;3:639-650.
7. th ed. (Hardman JG, Limbird LE, eds.), pp. 105-139. McGraw-Hill, New York, 1996.
8. Ostrowski J, Kjelsberg MA, Caron MG, Lefkowitz RJ: Mutagenesis of the β2-adrenergic receptor: how structure elucidates function. Annu Rev Pharmacol Toxicol 1992; 32:167-183.
9. Strader CD, Fong TM, Tota MR, Underwood D, Dixon RA: Structure and function of G protein-coupled receptors. Annu Rev Biochem 1994;63:101-132.
10. Gurrath M: Peptide-binding G protein-coupled receptors: new opportunities for drug design. Curr Med Chem 2001; 8:1605-1648.
11. Blake AD, Bot G, Reisine T: Structure-function analysis of the cloned opiate receptors: peptide and small molecule interactions. Chem Biol 1996;3:967-972.
12. Reisine T, Bell GI: Molecular biology of somatostatin receptors. Endocr Rev 1995;16:427-442.
13. Reisine T: Pharmacogenomics of opioid systems. In: Pharmacogenomics: The Search for Individualized Therapies (Licinio J, Wong M, eds.), pp. 461-487. Wiley-VCH, Weinheim, Germany, 2002.
14. th ed. (Hardman JG, Limbird LE, eds.j, pp. 521-555. McGraw-Hill, New York, 1996.
15. DeHaven RN, Mansson E, Daubert JD, Cassel JA: Pharmacological characterization of human kappa/mu opioid receptor chimeras that retain high affinity for dynorphin A. Curr Top Med Chem 2005;5:303-313.
16. Zhang L, DeHaven RN, Goodman M: NMR and modeling studies of a synthetic extracellular loop II of the kappa opioid receptor in a DPC micelle. Biochemistry 2002;41: 61-68.
17. Schlechtingen G, DeHaven RN, Daubert JD, Cassel JA, Chung NN, Schiller PW, et al.: Structure-activity relationships of dynorphin A analogues modified in the address sequence. J Med Chem 2003;46:2104-2109.
18. Blake AD, Bot G, Freeman JC, Reisine T: Differential opioid agonist regulation of the mouse μ, opioid receptor. J Biol Chem 1997;272:782-790.
19. Bohn LM, Dykstra L, Lefkowitz RJ, Caron M, Barak L: Relative opioid efficacy is determined by the complements of the G protein-coupled receptor desensitization machinery. Mol Pharmacol 2004;66:106-112.
20. 2 adrenergic receptor. Proc Natl Acad Sci U S A 2001;98:5997-6002.
21. 2-adrenoceptor: insights from fluorescence resonance energy tranfer studies. J Biol Chem Epub 2007 Mar 8; [Epub ahead of print].
22. Pitcher J, Freedman N, Lefkowitz RJ: G protein-coupled receptor kinases. Annu Rev Biochem 1998;67:653-692.
23. th ed. (Hardman JG, Limbird LE, eds.), pp. 29-41. McGraw-Hill, New York, 1996.
24. Simon M, Strathman M, Gautam N: Diversity of G proteins in signal transduction. Science 1991;252:802-808.
25. Dessauer CW, Posner BA, Gilman AG: Visualizing signal transduction: receptors, G proteins and adenylate cyclases. Clin Sci 1996;91:527-537.
26. Clapham DE, Neer E: New roles for G protein βγ-dimers in transmembrane signaling. Nature 1993;365: 403-406.
27. Neer EJ: Heterotrimeric G proteins: organizers of transmembrane signals. Cell 1995;80:249-257.
28. Limbird L: Receptors linked to inhibition of adenylate cyclase: additional signaling mechanisms. FASEB J 1988;2: 2686-2695.
29. Bylund D: Subtypes of alpha1 and alpha2-adrenergic receptors. FASEB J 1992;6:832-839.
30. Hunyady L, Vauquelin G, Vanderheyden P: Agonist induction and conformational selection during activation of a G-protein-coupled receptor. Trends Pharmacol Sci 2003;24:81-86.
31. Oliveira L, Paiva ACM, Vriend G: A low resolution model for the interaction of G proteins with G protein-coupled receptors. Protein Eng 1999;12:1087-1095.
32. Miller S, Vilo J, Croning MDR: Prediction of the coupling specificity of G protein coupled receptors to their G proteins. Bioinformatics 2001;17(Suppl):S174-S181.
33. Brown A, Birnbaumer L: Direct G protein gating of ion channels. Am J Physiol 1988;254:H401-H410.
34. Hille B: Ionic Channels of Excitable Membranes. Sinauer Associates, Sunderland, MA, 1992.
35. Yatani A, Codina J, Sekura R, Birnbaumer L, Brown A: Reconstitution of SRIF and muscarinic receptor mediated stimulation of K1 channels by isolated GK protein in clonal rat anterior pituitary membranes. Mol Endocrinol 1987;1:283-293.
36. ++ channels. Nature 1987;325:445-447.
37. Kleuss C, Hescheler J, Ewel C, Rosenthal W, Schultz G, Wittig B: Assignment of G protein subtypes to specific receptors inducing inhibition of calcium currents. Nature 1991;353:43-48.
38. Taussig R, Sanchez S, Rifo M, Gilman A, Belardetti F: Inhibition of the conotoxin-sensitive calcium current by distinct G proteins. Neuron 1992;8:799-809.
39. Berridge MJ: Inositol trisphosphate and calcium signaling. Nature 1993;361:315-325.
40. Lefkowitz RJ, Shenoy SK: Transduction of receptor signals by β-arrestins. Science 2005;308:512-517.
41. Carpenter G: Employment of the epidermal growth factor receptor in growth factor-independent signaling pathways. J Cell Biol 1999;146:697-702.
42. Reisine T, Law SF, Blake A, Tallent M: Molecular mechanisms of opiate receptor coupling to G proteins and effector systems. Ann N Y Acad Sci 1996;780:168-175.
43. Law SF, Reisine T: Changes in the association of G protein subunits with the cloned mouse delta opioid receptor on agonist stimulation. J Pharmacol Exp Ther 1997;281: 1476-1486.
44. o alpha selectively associate with the cloned somatostatin receptor subtype SSTR2. J Biol Chem 1993;268:10721-10727.
45. Law SF, Manning D, Reisine T: Identification of the subunits of GTP-binding proteins coupled to somatostatin receptors. J Biol Chem 1991;266:17885-17897.
46. Zhu W, Zeng W, Zheng M, Xiao R: The enigma of β2-adrenergic receptor Gi signaling in the heart: the good, the bad, and the ugly. Circ Res 2005;97:507-509.
47. 2+ channels in canine heart failure. Circ Res 2005;97:566-573.
48. Christopoulos A, Kenakin T: G protein-coupled receptor allosterism and complexing. Pharmacol Rev 2002;54: 323-374.
49. Christopoulos A: Allosteric binding sites on cell-surface receptors: novel targets for drug discovery. Nat Rev Drug Discov 2002;1:198-210.
50. 7/3-phth) at cloned muscarinic acetylcholine receptors. Biochem Pharmacol 1999;57:171-179.
51. May LT, Avlani VA, Sexton PM, Christopoulos A: Allosteric modulation of G protein coupled receptors. Curr Pharm Des 2004;10:2003-2013.
52. Luttrell LM, Lefkowitz RJ: The role of β-arrestins in the termination and transduction of G-protein-coupled receptor signals. J Cell Sci 2002;115:455-465.
53. Cliang A, Laporte SA, Caron M, Lefkowitz RJ: Endocytosis of G protein-coupled receptors: roles of G protein-coupled receptor kinases and beta-arrestin proteins. Prog Neurobiol 2002;66:61-79.
54. Shenoy SK, Lefkowitz RJ: Trafficking patterns of beta-arrestin and G protein-coupled receptors determined by the kinetics of beta-arrestin deubiquitination. J Biol Chem 2003;278:14498-14506.
55. Shenoy SK, Lefkowitz RJ: Receptor-specific ubiquitination of β-arrestin directs assembly and targeting of seven-transmembrane receptor signalosomes. J Biol Chem 2005; 280:15315-15324.
56. Zhang J, Barak LS, Anborgh PH, Laporte SA, Caron MG, Ferguson SS: Cellular trafficking of G protein-coupled receptor/beta-arrestin endocytic complexes. J Biol Chem 1999;274:10999-11006.
57. Shenoy SK, McDonald P, Kohout T, Lefkowitz RJ: Regulation of receptor fate by ubiquitination of activated beta 2-adrenergic receptor and beta-arrestin. Science 2001;294: 1307-1313.
58. Bohn LM, Lefkowitz RJ, Gainetdinov RR, Peppel K, Caron MG, Lin FT: Enhanced morphine analgesia in mice lacking beta-arrestin 2. Science 1999;286:2495-2498.
59. Bohn LM, Gainetdinov RR, Lin FT, Lefkowitz RJ, Caron MG: Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence. Nature 2000;408:720-723.
60. Gainetdinov RR, Premont RT, Bohn LM, Lefkowitz RJ, Caron MG: Desensitization of G protein-coupled receptors and neuronal functions. Annu Rev Neurosci 2004;27: 107-144.
61. Kroeze WK, Sheffler DJ, Roth BL: G-protein-coupled receptors at a glance. J Cell Sci 2003;116:4867-4869.
62. Azzi M, Charest PG, Angers S, Rousseau G, Kohout T, Bouvier M, et al.: Beta-arrestin-mediated activation of MAPK by inverse agonists reveals distinct active conformations for G protein-coupled receptors. Proc Natl Acad Sci U S A 2003;100:11406-11411.
63. Breitwieser G: G protein-coupled receptor oligomerization: implications for G protein activation and cell signaling. Circ Res 2004;94:17-27.
64. Angers S, Salahpour A, Bouvier M: Dimerization: an emerging concept for G protein-coupled receptor ontogeny and function. Annu Rev Pharmacol Toxicol 2002; 42:409-435.
65. Bouvier M: Oligomerization of G-protein-coupled transmitter receptors. Nat Rev Neurosci 2001;2:274-286.
66. Milligan G, Bouvier M: Methods to monitor the quaternary structure of G protein-coupled receptors. FEBS J 2005;272:2914-2925.
67. George S, O'Dowd B, Lee S: G-protein-coupled receptor oligomerization and its potential for drug discovery. Nat Rev Drug Discov 2002;1:808-820.
68. Cheifetz S, Hernandez H, Laiho M, ten Dijke P, Iwata KK, Massague J: Distinct transforming growth factor-α (TGFα-3) receptor subsets as determinants of cellular responsiveness to three TGF-α isoforms. J Biol Chem 1990; 265:20533-20538.
69. Marsters SA, Pennica D, Bach E, Schreiber R, Ashkenzai A: Interferon gamma signals via a high-affinity multisubunit receptor complex that contains two types of polypeptide chain. Proc Natl Acad Sci U S A 1995;92: 5401-5405.
70. Moustakas A, Lin H, Plamondon Y, O'Connor-McCourt M, Lodish H: The transforming growth factor j3 receptors types I, 11, and I11 form hetero-oligomeric complexes in the presence of ligand. J Biol Chem 1993; 268:22215-22218.
71. Muthukumaran G, Kotenko S, Donnelly R, Ihle J, Pestka S: Chimeric erythropoietin-interferon gamma receptors reveal differences in functional architecture of intracellular domains for signal transduction. J Biol Chem 1997; 272:4993-4999.
72. Wells R, Yankelev H, Lin H, Lodish H: Biosynthesis of the type I and type II TGF-β receptors. Implications for complex formation. J Biol Chem 1997;272:11444-11451.
73. 2-terminal kinase-1 is critical for PDGF-induced p21WAF1/CIP1 promoter activity independent of p53. J Biol Chem 2003;278: 49582-49588.
74. Wickman K, Clapham D: Ion channel regulation by G proteins. Physiol Rev 1995;75:865-885.
75. Salim K, Fenton T, Bacha J, Urien-Rodriguez H, Bonnert T, Skynner HA, et al.: Oligomerization of G-protein-coupled receptors shown by selective co-immunoprecipitation. J Biol Chem 2002;277:15482-15485.
76. Chidiac P, Hebert TE, Valiquette M, Dennis M, Bouvier M: Inverse agonist activity of beta-adrenergic antagonists. Mol Pharmacol 1994;45:490-499.
77. Bouaboula M, Perrachon S, Milligan L, Canat X, Rinaldi-Carmona M, Portier M, et al.: A selective inverse agonist for central cannabinoid receptor inhibits mitogen-activated protein kinase activation stimulated by insulin or insulin-like growth factor 1. Evidence for a new model of receptor/ligand interactions. J Biol Chem 1997;272: 22330-22339.
78. Befort K, Zilliox C, Filliol D, Yue SY, Kieffer B: Constitutive activation of the delta opioid receptor by mutations in transmembrane domains III and VII. J Biol Chem 1999;274:18574-18581.
79. Ren Q, Kurose H, Lefkowitz RJ, Cotecchia S: Constitutively active mutants of the alpha 2-adrenergic receptor. J Biol Chem 1993;268:16483-16487.
80. Samama P, Cotecchia S, Costa T, Lefkowitz RJ: A mutation-induced activated state of the beta 2-adrenergic receptor. Extending the ternary complex model. J Biol Chem 1993;268:4625-4636.
81. Tiberi M, Caron M: High agonist-independent activity is a distinguishing feature of the dopamine DIB receptor subtype. J Biol Chem 1994;269:27925-27931.
82. Smit MJ, Leurs R, Alewijnse AE, Blauw J, Van Nieuw Amerongen GP, Van De Vrede Y, et al.: Inverse agonism of histamine H2 antagonist accounts for up-regulation of spontaneously active histamine H2 receptors. Proc Natl Acad Sci U S A 1996;93:6802-6807.
83. Kudo M, Osuga Y, Kobilka BK, Hsueh AJ: Transmembrane regions V and VI of the human luteinizing hormone receptor are required for constitutive activation by a mutation in the third intracellular loop. J Biol Chem 1996; 271:22470-22478.
84. Scheer A, Fanelli F, Costa T, De Benedetti P, Cotecchia S: The activation process of the alpha1B-adrenergic receptor: potential role of protonation and hydrophobicity of a highly conserved aspartate. Proc Natl Acad Sci U S A 1997;94:808-813.
85. Spiegel AM: Defects in G protein-coupled signal transduction in human disease. Annu Rev Physiol 1996;58: 143-170.
86. Wonerow P, Schineberg T, Schultz G, Gudermann T, Paschke R: Deletions in the third intracellular loop of the thyrotropin receptor. A new mechanism for constitutive activation. J Biol Chem 1998;273:7900-7905.
87. Zuscik MJ, Porter JE, Gaivin R, Perez DM: Identification of a conserved switch residue responsible for selective constitutive activation of the beta2-adrenergic receptor. J Biol Chem 1998;273:3401-3407.
88. 1 receptor heterodimers in preeclampsia mediate enhanced angiotensin II responsiveness. Nat Med 2001;7:1003-1009.
89. AbdAlla S, Lother H, Quitterer U: AT1-receptor heterodimers show enhanced G-protein activation and altered receptor sequestration. Nature 2000;407:94-98.
90. Kniazeff J, Galvez T, Labesse G, Pin J-P: No ligand binding in the GB2 subunit of the GABAB receptor is required for activation and allosteric interaction between subunits. J Neurosci 2002;22:7352-7361.
91. B receptor heterodimerization. Neuron 2000;27:97-106.
92. Galvez T, Duthey B, Kniazeff J, Blahos J, Rovelli G, Bettier B, et al.: Allosteric interactions between GB1 and GB2 subunits are required for optimal GABAB receptor function. EMBO J 2001;20:2152-2159.
93. Margeta-Mitrovic M, Jan YN, Jan LY: Function of GB1 and GB2 subunits in G protein coupling of GABAB receptors. Proc Natl Acad Sci U S A 2001;98:14649-14654.
94. Duthey B, Caudron S, Perroy J, Bettler B, Fagni L, Pin J-P, et al.: A single subunit (GB2) is required for G-protein activation by the heterodimeric GABAB receptor. J Biol Chem 2002;277:3236-3241.
95. Robbins MJ, Calver AR, Filippov AK, Hirst WD, Russell RB, Wood MD, et al.: GABAB2 is essential for G-protein coupling of the GABAB receptor heterodimer. J Neurosci 2001;21:8043-8052.
96. Breit A, Lagace M, Bouvier M: Hetero-oligomerization between beta2- and beta3-adrenergic receptors generates a beta-adrenergic signaling unit with distinct functional properties. J Biol Chem 2004;279:28756-28765.
97. Mellado M, Rodriguez-Frade JM, Vila-Coro A, Fernandez S, Martin de Ana A, Jones DR, et al.: Chemokine receptor homo- or heterodimerization activates distinct signaling pathways. EMBO J 2001;20:2497-2507.
98. Lee DK, Lanca AJ, Cheng R, Nguyen T, Ji XD, Gobeil F Jr, et al.: Agonist-independent nuclear localization of the Apelin, angiotensin AT1, and bradykinin B2 receptors. J Biol Chem 2004;279:7901-7908.
99. So CH, Varghese G, Curley K, Kong M, Alijaniaram M, Ji X, et al.: D1 and D2 dopamine receptors form heterooligomers and cointernalize after selective activation of either receptor. Mol Pharmacol 2005;68:568-578.
100. Hilairet S, Bouaboula M, Carriere D, Le Fur G, Casellas P: Hypersensitization of the orexin 1 receptor by the CB1 receptor: evidence for cross-talk blocked by the specific CB1 antagonist, SR141716. J Biol Chem 2003;278: 23731-23737.
101. George SR, Fan T, Xie Z, Tse R, Tam V, Varghese G, O'Dowd BF: Oligomerization of μ- and δ-opioid receptors. Generation of novel functional properties. J Biol Chem 2000;275:26128-26135.
102. Sautel M, Milligan G: Molecular manipulation of G-protein-coupled receptors: a new avenue into drug discovery. Curr Med Chem 2000;7:889-896.
103. James JR, Oliveira M, Carmo A, Iaboni A, Davis S: A rigorous experimental framework for detecting protein oligomerization using bioluminescence resonance energy transfer. Nat Methods 2006;3:1001-1006.
104. Stadel J, Wilson S, Bergsma D: Orphan G protein-coupled receptors: a neglected opportunity for pioneer drug discovery. Trends Pharmacol Sci 1997;18:430-437.
105. Lee DK, George SR, Evans JF, Lynch KR, O'Dowd BF: Orphan G protein-coupled receptors in the CNS. Curr Opin Pharmacol 2001;1:31-39.
106. Morris I, Williams R: Research strategies for orphan G-protein-coupled receptors. Drug News Perspect 2002;15: 249-252.
107. Meunier JC, Mollereau C, Toll L, Suaudeau C, Moisand C, Alvinerie P, et al.: Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor. Nature 1995;377:532-535.
108. Reinscheid R, Nothacker H, Bourson A, Ardati A, Henningsen RA, Bunzow JR, et al.: Orphanin FQ: a neuropeptide that activates an opioidlike G protein-coupled receptor. Science 1995;270:792-794.
109. Ames RS, Sarau HM, Chambers JK, Willette RN, Aiyar NV, Romanic AM, et al.: Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14. Nature 1999;401:282-286.
110. Lynch KR, O'Neill GP, Liu Q, Im DS, Sawyer N, Metters KM, et al.: Characterization of the human cysteinyl leukotriene CysLT1 receptor. Nature 1999;399:789-793.
111. Spiegel AM, Weinstein L: Inherited diseases involving G proteins and GPCRs. Annu Rev Med 2004;55:27-39.
112. Lee A, Rana BK, Schiffer HH, Lee A, Rana BK, Schiffer HH, et al.: Distribution analysis of non-synonymous polymorphisms within the G-protein coupled receptor gene family. Genomics 2003;81:245-248.
113. Jordan N, Williams N, Gregory JW, Evans C, Owen M, Ludgate M: The W546X mutation of the thyrotropin receptor gene: potential major contributor to thyroid dysfunction in a Caucasian population. J Clin Endocrinol Metab 2003;88:1002-1005.
114. Carrasquillo MM, McCallion AS, Puffenberger EG, Kashuk CS, Nouri N, Chakravarti A: Genome-wide association study and mouse model identify interaction between RET and EDNRB pathways in Hirschsprung disease. Nat Genet 2002;32:237-244.
115. Wysolmerski JJ, Cormier S, Philbrick WM, Dann P, Zhang JP, Roume J, et al.: Absence of functional type 1 parathyroid hormone (PTH)/PTH-related protein receptors in humans is associated with abnormal breast development and tooth impaction. J Clin Endocrinol Metab 2001;86:1487-1488.
116. Liu R, Paxton WA, Choe S, Ceradini D, Martin SR, Horuk R, et al.: Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply exposed individuals to HIV-1 infection. Cell 1996;86:367-377.
117. Schulz A, Sangkuhl K, Lennert T, Wigger M, Price DA, Nuuja A, et al.: Aminoglycoside pretreatment partially restores the function of truncated V2 vasopressin receptors found in patients with nephrogenic diabetes insipidus. J Clin Endocrinol Metab 2002;87:5247-5257.
118. Morello J-P, Salahpour A, Laperriere A, Bernier V, Arthus MF, Lonergan M, et al.: Pharmacological chaperones rescue cell-surface expression and function of misfolded V2 vasopressin receptor mutants. J Clin Invest 2000;105:887-895.
119. Bernier V, Lagace M, Lonergan M, Arthus MF, Bichet DG, Bouvier M: Functional rescue of the constitutively internalized V2 vasopressin receptor mutant R137H by the pharmacological chaperone action of SR49059. Mol Endocrinol 2004;18:2074-2084.
120. Janovick JA, Goulet M, Bush E, Greer J, Wettlaufer DG, Conn P: Structure-activity relations of successful pharmacologic chaperones for rescue of naturally occurring and manufactured mutants of gonadotropin-releasing hormone receptor. J Pharmacol Exp Ther 2003;305:608-614.
121. Ulloa-Aguirre A, Janovick J, Brothers S, Conn P: Pharmacologic rescue of conformationally-defective proteins: implications for the treatment of human disease Traffic 2004;5:821-837.
122. Gelman MS, Kopito RR: Rescuing protein conformation: prospects for pharmacological therapy in cystic fibrosis. J Clin Invest 2002;110:1591-1597.
123. Berson EL: Retinitis pigmentosa and allied diseases. In: Principles and Practice of Ophthalmology (Albert DM, Jakobiec FA, Azar DT, Gragoudas ES, eds.), pp. 2262-2290. Saunders, Philadelphia, 2002.
124. Calvi LM, Schipani E: The PTH/PTHrP receptor in Jansen's metaphyseal chondrodysplasia. J Endocrinol Invest 2000;23:545-554.
125. Corvilain B, Van Sande J, Dumont JE, Vassert G: Somatic and germline mutations of the TSH receptor and thyroid diseases. Clin Endocrinol 2001;55:143-158.
126. Themmen AP, Verhoef-Post M: LH receptor defects. Semin Reprod Med 2002;20:199-204.
127. 2+-sensing receptor: implications for its structure and function. Trends Endocrinol Metab 2003;14: 282-288.
128. Strosberg AD: Association of beta 3-adrenoceptor polymorphism with obesity and diabetes: current status. Trends Pharmacol Sci 1997;18:449-454.
129. Pietri-Rouxel F, St. John Manning B, Gros J, Strosberg A: The biochemical effect of the naturally occurring Trp64 → Arg mutation on human beta3-adrenoceptor activity. Eur J Biochem 1997;247:1174-1179.
130. Small KM, Wagoner LE: Synergistic polymorphisms of α1- and β2c-adrenergic receptors and the risk of congestive heart failure. N Engl J Med 2002;347:1135-1142.
131. Kammermeirer PJ, Xiao B, Tu JC, Worley PF, Ikeda SR: Homer proteins regulate coupling of group 1 metabotropic glutamate receptors to N-type calcium and M-type potassium channels. J Neurosci 2000;20:7238-7245.
132. Ango F, Pin JP, Tu JC, Xiao B, Worley PF, Bockaert J, et al.: Dendritic and axonal targeting of type 5 metabotropic glutamate receptor is regulated by Homer1 proteins and neuronal excitation. J Neurosci 2000;20:8710-8716.
133. Ango F, Robbe D, Tu JC, Xiao B, Worley PF, Pin JP, et al.: Homer-dependent cell surface expression of metabotropic glutamate receptor type 5 in neurons. Mol Cell Neurosci 2002;20:323-329.
134. Brakeman PR, Lanahan AA, O'Brien R, Roche K, Barnes CA, Huganir RL, et al.: Homer: a protein that selectively binds metabotropic glutamate receptors. Nature 1997;386: 284-288.
135. Xiao B, Tu JC, Petralia RS, Yuan JP, Doan A, Breder CD, et al.: Homer regulates the association of group I metabotropic glutamate receptors with multivalent complexes of Homer-related, synaptic proteins. Neuron 1998;21:707-716.
136. Xiao B, Tu JC, Worley PF: Homer: a link between neural activity and glutamate receptor function. Curr Opin Neurobiol 2000;10:370-374.
137. Ango F, Prezeau L, Muller T, Tu JC, Xiao B, Worley PF, et al.: Agonist-independent activation of metabotropic glutamate receptors by the intracellular protein Homer. Nature 2001;411:962-965.
138. Chiamulera C, Epping-Jordan MP, Zocchi A, Marcon C, Cottiny C, Tacconi S, et al.: Reinforcing and locomotor stimulant effects of cocaine are absent in mGluR5 null mutant mice. Nat Neurosci 2001;4:873-874.
139. Tessari M, Pilla M, Andreoli M, Hutcheson DM, Heidbreder CA: Antagonism at metabotropic glutamate 5 receptors inhibits nicotine- and cocaine-taking behaviors and prevents nicotine-triggered relapse to nicotine-seeking. Eur J Pharmacol 2004;499:121-133.
140. Liebmann C: G protein-coupled receptors and their signaling pathways: classical therapeutical targets susceptible to novel therapeutic concepts. Curr Pharm Des 2004;10:1937-1958.
141. Christopoulos A, Christopoulos G, Mortis M, Udawela M, Laburthe M, Couvineau A, et al.: Novel receptor partners and function of receptor activity-modifying proteins. J Biol Chem 2003;278:3293-3297.
142. McLatchie LM, Fraser NJ, Main MJ, Wise A, Brown J, Thompson N, et al.: RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature 1998;393:333-339.
143. Fraser NJ, Wise A, Brown J, McLatchie L, Main M, Foord S: The amino terminus of receptor activity modifying proteins is a critical determinant of glycosylation state and ligand binding of calcitonin receptor-like receptor. Mol Pharmacol 1999;55:1054-1059.
144. Flahaut M, Rossier BC, Firsov D: Respective roles of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMP) in cell surface expression of CRLR/RAMP heterodimeric receptors. J Biol Chem 2002;277:14731-14737.
145. Kuwasako K, Kitamura K, Nagoshi Y, Cao YN, Eto T: Identification of the human receptor activity-modifying proteinl domains responsible for agonist binding specificity. J Biol Chem 2003;278:22623-22630.
146. Mallee JJ, Salvatore C, LeBourdelles B, Oliver K, Long-more J, Koblan K, et al.: Receptor activity-modifying protein 1 determines the species selectivity of non-peptide CGRP receptor antagonists. J Biol Chem 2002;277: 14294-14298.
147. Kenakin T, Bond R, Bonner T: Definition of pharmacological receptors. Pharmacol Rev 1992;44:351-362.
148. Bylund D, Deupree JD, Toews ML: Radioligand-binding methods for membrane preparations and intact cells. Methods Mol Biol 2004;259:1-28.
149. Nouel D, Gaudriault G, Houle M, Reisine T, Vincent JP, Mazella J, Beaudet A: Differential internalization of somatostatin in COS-7 cells transfected with SST1 and SST2 receptor subtypes: a confocal microscopic study using novel fluorescent somatostatin derivatives. Endocrinology 1997;138:296-306.
150. i-linked G protein-coupled receptors. Assay Drug Dev Technol 2003;1:261-273.
151. i/o-linked ADP receptors in the nervous system: close similarities with the platelet P2Y(ADP) receptor. J Neurochem 2001;77:505-518.
152. 35S]GTPγS binding assay: approaches and applications in pharmacology. Life Sci 2003;74:489-508.
153. Milligan G, Feng GJ, Ward RJ, Sartania N, Ramsay D, McLean AJ, et al.: G protein-coupled receptor fusion proteins in drug discovery. Curr Pharm Des 2004;10: 1989-2001.
154. Pascal G, Milligan G: Functional complementation and the analysis of opioid receptor homodimerization. Mol Pharmacol 2005;68:905-915.
155. 35S]GTPγS scintillation proximity assay: a powerful emerging technique for analysis of GPCR pharmacology. Trends Pharmacol Sci 2004;25:400-401.
156. Rees S: Functional assay systems for drug discovery at G-protein coupled receptors and ion channels. Receptors Channels 2002;8:257-259.
157. Kunapuli P, Ransom R, Murphy KL, Pettibone D, Kerby J, Grimwood S, et al.: Development of an intact cell reporter gene beta-lactamase assay for G protein-coupled receptors for high-throughput screening. Anal Biochem 2003:314:16-29.
158. Kornienko O, Lacson P, Kunapuli P, Schneewels J, Hoffman I, Smith T, et al.: Miniaturization of whole live cell-based GPCR assays using microdispensing and detection systems. J Biomol Screen 2004;9:186-195.
159. Williams C: cAMP detection methods in HTS: selecting the best from the rest. Nat Rev Drug Discov 2004;3:125-135.
160. Goetz AS, Liacos J, Yingling J, Ignar DM: A combination assay for simultaneous assessment of multiple signaling pathways. J Pharmacol Toxicol Methods 1999;42: 225-235.
161. Chambers C, Smith F, Williams C, Marcos S, Liu ZH, Hayter P, et al.: Measuring intracellular calcium fluxes in high throughput mode. Comb Chem High Throughput Screen 2003;6:355-362.
162. Kassack MU, Hoefgen B, Lehmann J, Eckstein N, Quillan JM, Sadee W: Functional screening of G protein-coupled receptors by measuring intracellular calcium with a fluorescence microplate reader. J Biomol Screen 2002;7: 233-246.
163. Zhang Y, Kowal D, Kramer A, Dunlop J: Evaluation of FLIPR Calcium 3 Assay Kit - a new no-wash fluorescence calcium indicator reagent. J Biomol Screen 2003;8: 571-577.
164. Dupriez V, Maes K, Le Poul E, Burgeon E, Detheux M: Aequorin-based functional assays for G-protein-coupled receptors, ion channels, and tyrosine kinase receptors. Receptors Channels 2002;8:319-330.
165. Le Poul E, Hisada S, Miziguchi Y, Dupriez VJ, Burgeon E, Detheux M: Adaptation of aequorin functional assay to high throughput screening. J Biomol Screen 2002;7: 57-65.
166. Offermanns S, Simon MI: G alpha15 and G alpha16 couple a wide variety of receptors to phospholipase C. J Biol Chem 1995;270:15175-15180.
167. Coward P, Chan S, Wada HG, Humphries GM, Conklin BR: Chimeric G proteins allow a high-throughput signaling assay of Gi-coupled receptors. Anal Biochem 1999; 270:242-248.
168. Liu R, Paxton WA, Choe S, Ceradini D, Martin SR, Horuk R, et al.: Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply exposed individuals to HIV-1 infection. Cell 1996;86:367-377.
169. Kostensis EJ: Potentiation of GPCR-signaling via membrane targeting of G protein alpha subunits. Receptor Signal Trans 2002;22:267-281.
170. Weiner DM, Burstein ES, Nash N, Croston GE, Currier EA, Vanover KE, et al.: 5-Hydroxytryptamine2A receptor inverse agonists as antipsychotics. J Pharmacol Exp Ther 2001;299:268-276.
171. Smit MJ, Baker RA, Burstein ES: G-protein coupled receptors and proliferative signaling. Methods Enzymol 2002;343:430-447.
172. Spalding TA, Trotter C, Skaerbaek N, Messier TL, Currier EA, Burstein ES, et al.: Discovery of an ectopic activation site on the M1 muscarinic receptor. Mol Pharmacol 2002;61:1297-1302.
173. Behan DP, Chalmers DT: The use of constitutively active receptors for drug discovery at the G protein-coupled receptor gene pool. Curr Opin Drug Discov Dev 2001;4: 548-560.
174. Lerner MR: Tools for investigating functional interactions between ligands and G-protein-coupled receptors. Trends Neurosci 1994;17:142-146.
175. Barak LS, Ferguson SS, Zhang J, Caron MG: A beta-arrestin/GFP biosensor for detecting GPCR activation. J Biol Chem 1997;272:27497-27500.
176. Kim KM, Valenzano KJ, Robinson SR, Yao WD, Barak LS, Caron MG: Differential regulation of dopamine D2 and D3 receptors by G protein-coupled receptor kinases and beta-arrestins. J Biol Chem 2001;276:37409-37414.
177. Bertrand L, Parent S, Caron M, Legault M, Mireille J, Erik A, et al.: The BRET2/arrestin assay in stable recombinant cells: a platform to
178. Heding A: Use of BRET 7TM receptor/beta arrestin assay in drug discovery and screening. Expert Rev Mol Diagn 2004;3:403-411.
179. Vrecl M, Jorgensen R, Pogacnik A, Heding A: Development of a BRET2 screening assay using beta-arrestin 2 mutants. J Biomol Screen 2004;4:322-333.
180. Wehrman TS, Casipit CL, Gewertz NM, Blau HM: Enzymatic detection of protein translocation. Nat Methods 2005;2:521-527.
181. O'Dowd BF, Ji X, Alijaniaram M, Rajaram RD, Kong MM, Rashid A, et al.: Dopamine receptor oligomerization visualized in living cells. J Biol Chem 2005;280: 37225-37235.
182. Lu D, Yang H, Shaw G, Raizada M: Angiotensin II-induced nuclear targeting of the angiotensin type 1 (AT1) receptor in brain neurons. Endocrinology 1998;139:365-375.
183. Watson P, Fraher L, Natale B, Kisiel M., Hendy G, Hodsman A: Nuclear localization of the type 1 parathyroid hormone/parathyroid hormone-related peptide receptor in MC3T3-E1 cells: association with serum-induced cell proliferation. Bone 2000;26:221-225.
184. 2+ changes in heterologous cell types and neurons. J Biol Chem 2003;278:28210-28219.
185. Bhattacharya M, Peri KG, Almazan G, Ribeiro-da-Silva A, Shichi H, Durocher Y, et al.: Nuclear localization of prostaglandin E2 receptors. Proc Natl Acad Sci U S A 1998;95:15792-15797.
186. Bhattacharya M, Peri K, Ribeiro-da-Silva A, Almazan G, Shichi H, Hou X, et al.: Localization of functional prostaglandin E2 receptors EP3 and EP4 in the nuclear envelope. J Biol Chem 1999;274:15719-15724.
187. Boivin B, Chevalier D, Villeneuve LR, Rousseau E, Allen BG: Functional endothelin receptors are present on nuclei in cardiac ventricular myocytes. J Biol Chem 2003;278: 29153-29163.
188. Cooper MA: Non-optical screening platforms: the next wave in label-free screening? Drug Discov Today 2006; 11:1068-1074.
189. Cooper MA: Optical biosensors: where next and how soon? Drug Discov Today 2006;11:1061-1067.