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The structural basis of g-protein-coupled receptor function and dysfunction in human diseases

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References

  • AbdAlla S, Zaki E, Lother H, Quitterer U (1999) Involvement of the amino terminus of the B2 receptor in agonist-induced receptor dimerization. J Biol Chem 274:26079–84

    PubMed  CAS  Google Scholar 

  • AbdAlla S, Lother H, Quitterer U (2000) AT1-receptor heterodimers show enhanced G-protein activation and altered receptor sequestration. Nature 407:94–8

    PubMed  CAS  Google Scholar 

  • Abdulaev NG, Ridge KD (1998) Light-induced exposure of the cytoplasmic end of transmembrane helix seven in rhodopsin. Proc Natl Acad Sci USA 95:12854–9

    PubMed  CAS  Google Scholar 

  • Abell AN, Segaloff DL (1977) Evidence for the direct involvement of transmembrane region 6 of the lutropin/choriogonadotropin receptor in activating Gs. J Biol Chem 272:14586–91

    Google Scholar 

  • Abell AN, McCormick DJ, Segaloff DL (1998) Certain activating mutations within helix 6 of the human luteinizing hormone receptor may be explained by alterations that allow transmembrane regions to activate Gs. Mol Endocrinol 12:1857–69

    PubMed  CAS  Google Scholar 

  • Accili D, Fishburn CS, Drago J, Steiner H, Lachowicz JE, Park BH, Gauda EB, Lee EJ, Cool MH, Sibley DR, Gerfen CR, Westphal H, Fuchs S (1996) A targeted mutation of the D3 dopamine receptor gene is associated with hyperactivity in mice. Proc Natl Acad Sci USA 93:1945–9

    PubMed  CAS  Google Scholar 

  • Acharya S, Karnik SS (1996) Modulation of GDP release from transducin by the conserved Glu134-Arg135 sequence in rhodopsin. J Biol Chem 271:25406–11

    PubMed  CAS  Google Scholar 

  • Aittomaki K, Lucena JL, Pakarinen P, Sistonen P, Tapanainen J, Gromoll J, Kaskikari R, Sankila EM, Lehvaslaiho H, Engel AR (1995) Mutation in the folliclestimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell 82:959–68

    PubMed  CAS  Google Scholar 

  • Albertazzi E, Zanchetta D, Barbier P, Faranda S, Frattini A, Vezzoni P, Procaccio M, Bettinelli A, Guzzi F, Parenti M, Chini B (2000) Nephrogenic diabetes insipidus: functional analysis of new AVPR2 mutations identified in Italian families. J Am Soc Nephrol 11:1033–43

    PubMed  CAS  Google Scholar 

  • Alblas J, van Etten I, Khanum A, Moolenaar WH (1995) C-terminal truncation of the neurokinin-2 receptor causes enhanced and sustained agonist-induced signaling. Role of receptor phosphorylation in signal attenuation. J Biol Chem 270:8944–51

    PubMed  CAS  Google Scholar 

  • Alewijnse AE, Timmerman H, Jacobs EH, Smit MJ, Roovers E, Cotecchia S, Leurs R (2000) The effect of mutations in the DRY motif on the constitutive activity and structural instability of the histamine H2 receptor. Mol Pharmacol 57:890–8

    PubMed  CAS  Google Scholar 

  • Alexeev V, Igoucheva O, Domashenko A, Cotsarelis G, Yoon K (2000) Localized in vivo genotypic and phenotypic correction of the albino mutation in skin by RNA-DNA oligonucleotide. Nat Biotechnol 18:43–7

    PubMed  CAS  Google Scholar 

  • Allen LF, Lefkowitz RJ, Caron MG, Cotecchia S (1991) G-protein-coupled receptor genes as protooncogenes: constitutively activating mutation of the α1B-adrenergic receptor enhances mitogenesis and tumorigenicity. Proc Natl Acad Sci USA 88:11354–8

    PubMed  CAS  Google Scholar 

  • al-Maghtheh M, Gregory C, Inglehearn C, Hardcastle A, Bhattacharya S (1993) Rhodopsin mutations in autosomal dominant retinitis pigmentosa. Hum Mutat 2:249–55

    PubMed  CAS  Google Scholar 

  • Altenbach C, Yang K, Farrens DL, Farahbakhsh ZT, Khorana HG, Hubbell WL (1996) Structural features and light-dependent changes in the cytoplasmic interhelical E-F loop region of rhodopsin: a site-directed spin-labeling study. Biochemistry 35:12470–8

    PubMed  CAS  Google Scholar 

  • Amatruda TT, Dragas-Graonic S, Holmes R, Perez HD (1995) Signal transduction by the formyl peptide receptor. Studies using chimeric receptors and site-directed mutagenesis define a novel domain for interaction with G-proteins. J Biol Chem 270:28010–3

    PubMed  CAS  Google Scholar 

  • Angers S, Salahpour A, Joly E, Hilairet S, Chelsky D, Dennis M, Bouvier M (2000) Detection of β2-adrenergic receptor dimerization in living cells using bioluminescence resonance energy transfer (BRET). Proc Natl Acad Sci USA 97:3684–9

    PubMed  CAS  Google Scholar 

  • Ango F, Prezeau L, Muller T, Tu JC, Xiao B, Worley PF, Pin JP, Bockaert J, Fagni L (2001) Agonist-independent activation of metabotropic glutamate receptors by the intracellular protein Homer. Nature 411:962–5

    PubMed  CAS  Google Scholar 

  • Ardati A, Goetschy V, Gottowick J, Henriot S, Valdenaire O, Deuschle U, Kilpatrick GJ (1999) Human CRF2 and β splice variants: pharmacological characterization using radioligand binding and a luciferase gene expression assay. Neuropharmacology 38:441–8

    PubMed  CAS  Google Scholar 

  • Arora KK, Cheng Z, Catt KJ (1997) Mutations of the conserved DRS motif in the second intracellular loop of the gonadotropin-releasing hormone receptor affect expression, activation, and internalization. Mol Endocrinol 11:1203–12

    PubMed  CAS  Google Scholar 

  • Arranz MJ, Munro J, Owen MJ, Spurlock G, Sham PC, Zhao J, Kirov G, Collier DA, Kerwin RW (1998) Evidence for association between polymorphisms in the promoter and coding regions of the 5-HT2A receptor gene and response to clozapine. Mol Psychiatry 3:61–6

    PubMed  CAS  Google Scholar 

  • Arthus MF, Lonergan M, Crumley MJ, Naumova AK, Morin D, De Marco LA, Kaplan BS, Robertson GL, Sasaki S, Morgan K, Bichet DG, Fujiwara TM (2000) Report of 33 novel AVPR2 mutations and analysis of 117 families with X-linked nephrogenic diabetes insipidus. J Am Soc Nephrol 11:1044–54

    PubMed  CAS  Google Scholar 

  • Arvanitakis L, Geras-Raaka E, Varma A, Gershengorn MC, Cesarman E (1997) Human herpesvirus KSHV encodes a constitutively active G-protein-coupled receptor linked to cell proliferation. Nature 385:347–50

    PubMed  CAS  Google Scholar 

  • Avissar S, Amitai G, Sokolovsky M (1983) Oligomeric structure of muscarinic receptors is shown by photoaffinity labeling: subunit assembly may explain high-and low-affinity agonist states. Proc Natl Acad Sci USA 80:156–9

    PubMed  CAS  Google Scholar 

  • Bai J, Bishop JV, Carlson JO, DeMartini JC (1999) Sequence comparison of JSRV with endogenous proviruses: envelope genotypes and a novel ORF with similarity to a G-protein-coupled receptor. Virology 258:333–43

    PubMed  CAS  Google Scholar 

  • Bai M, Trivedi S, Brown EM (1998) Dimerization of the extracellular calcium-sensing receptor (CaR) on the cell surface of CaR-transfected HEK293 cells. J Biol Chem 273:23605–10

    PubMed  CAS  Google Scholar 

  • Baker EK, Colley NJ, Zuker CS (1994) The cyclophilin homolog NinaA functions as a chaperone, forming a stable complex in vivo with its protein target rhodopsin. EMBO J 13:4886–96

    PubMed  CAS  Google Scholar 

  • Baldwin JM (1994) Structure and function of receptors coupled to G proteins. Curr Opin Cell Biol 6:180–90

    PubMed  CAS  Google Scholar 

  • Ballesteros JA, Jensen AD, Liapakis G, Rasmussen SG, Shi L, Gether U, Javitch JA (2001) Activation of the β2-adrenergic receptor involves disruption of an ionic lock between the cytoplasmic ends of transmembrane semeents 3 and 6. J Biol Chem 276:29171–7

    PubMed  CAS  Google Scholar 

  • Barak LS, Oakley RH, Laporte SA, Caron MG (2001) Constitutive arrestin-mediated desensitization of a human vasopressin receptor mutant associated with nephrogenic diabetes insipidus. Proc Natl Acad Sci USA 98:93–8

    PubMed  CAS  Google Scholar 

  • Barbato G, Cicero DO, Nardi MC, Steinkuhler C, Cortese R, De Francesco R, Bazzo R (1999) The solution structure of the N-terminal proteinase domain of the hepatitis C virus (HCV) NS3 protein provides new insights into its activation and catalytic mechanism. J Mol Biol 289:371–84

    PubMed  CAS  Google Scholar 

  • Baron J, Winer KK, Yanovski JA, Cunningham AW, Laue L, Zimmerman D, Cutler GB Jr (1996) Mutations in the Ca2+-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism. Hum Mol Genet 5:601–6

    PubMed  CAS  Google Scholar 

  • Beamer WJ, Eicher EM, Maltais LJ, Southard JL (1981) Inherited primary hypothyroidism in mice. Science 212:61–3

    PubMed  CAS  Google Scholar 

  • Beau I, Touraine P, Meduri G, Gougeon A, Desroches A, Matuchansky C, Milgrom E, Kuttenn F, Misrahi M (1998) A novel phenotype related to partial loss of function mutations of the follicle stimulating hormone receptor. J Clin Invest 102:1352–9

    PubMed  CAS  Google Scholar 

  • Beck M, Sakmar TP, Siebert F (1998) Spectroscopic evidence for interaction between transmembrane helices 3 and 5 in rhodopsin. Biochemistry 37:7630–39

    PubMed  CAS  Google Scholar 

  • Beinborn M, Quinn SM, Kopin AS (1998) Minor modifications of a cholecystokinin-B/gastrin receptor non-peptide antagonist confer a broad spectrum of functional properties. J Biol Chem 273:14146–51

    PubMed  CAS  Google Scholar 

  • Benkirane M, Jin DY, Chun RF, Koup RA, Jeang KT (1997) Mechanism of transdominant inhibition of CCR5-mediated HIV-1 infection by ccr5Δ32. J Biol Chem 272:30603–6

    PubMed  CAS  Google Scholar 

  • Berkower C, Michaelis S (1991) Mutational analysis of the yeast a-factor transporter STE6, a member of the ATP binding cassette (ABC) protein superfamily. EMBO J 10:3777–85

    PubMed  CAS  Google Scholar 

  • Bermak JC, Li M, Bullock C, Zhou QY (2001) Regulation of transport of the dopamine D1 receptor by a new membrane-associated ER protein. Nat Cell Biol 3:492–8

    PubMed  CAS  Google Scholar 

  • Bessant DA, Khaliq S, Hameed A, Anwar K, Payne AM, Mehdi SQ, Bhattacharya SS (1999) Severe autosomal dominant retinitis pigmentosa caused by a novel rhodopsin mutation (Ter349Glu). Mutations in brief no. 208. Online. Hum Mutat 13:83

    PubMed  CAS  Google Scholar 

  • Bibi E, Kaback HR (1990) In vivo expression of the lacY gene in two segments leads to functional lac permease. Proc Natl Acad Sci USA 87:4325–9

    PubMed  CAS  Google Scholar 

  • Bichet DG (1998) Nephrogenic diabetes insipidus. Am J Med 105:431–42

    PubMed  CAS  Google Scholar 

  • Bichet DG, Birnbaumer M, Lonergan M, Arthus MF, Rosenthal W, Goodyer P, Nivet H, Benoit S, Giampietro P, Simonetti S, Fish A, Whitley CB, Jaeger P, Gertner J, New M, DiBona FJ, Kaplan BS, Robertson GL, Hendy GN, Fujiwara TM, Morgan K (1994) Nature and recurrence of AVPR2 mutations in X-linked nephrogenic diabetes insipidus. Am J Human Genetics 55:278–86

    CAS  Google Scholar 

  • Biebermann H, Grüters A, Schöneberg T, Gudermann T (1997) Congenital hypothyroidism caused by mutations in the thyrotropin-receptor gene. N Engl J Med 336:1390–1

    PubMed  CAS  Google Scholar 

  • Biebermann H, Schöneberg T, Schulz A, Krause G, Grüters A, Schultz G, Gudermann T (1998) A conserved tyrosine residue (Y601) in transmembrane domain 5 of the human thyrotropin receptor serves as a molecular switch to determine G-protein coupling. FASEB J 12:1461–71

    PubMed  CAS  Google Scholar 

  • Biebermann H, Schöneberg T, Hess C, Germak J, Gudermann T, Grüters A (2001) The first activating TSHR mutation in transmembrane domain 1 identified in a family with non-autoimmune hyperthyroidism. J Clin Endocrinol Metab 86:4429–33

    PubMed  CAS  Google Scholar 

  • Black DL (1998) Splicing in the inner ear: a familiar tune, but what are the instruments? Neuron 20:165–8

    PubMed  CAS  Google Scholar 

  • Blanpain C, Lee B, Vakili J, Doranz BJ, Govaerts C, Migeotte I, Sharron M, Dupriez V, Vassart G, Doms RW, Parmentier M (1999) Extracellular cysteines of CCR5 are required for chemokine binding, but dispensable for HIV-1 coreceptor activity. J Biol Chem 274:18902–8

    PubMed  CAS  Google Scholar 

  • Blin N, Yun J, Wess J (1995) Mapping of single amino acid residues required for selective activation of Gq/11 by the m3 muscarinic acetylcholine receptor. J Biol Chem 270:17741–8

    PubMed  CAS  Google Scholar 

  • Blüml K, Mutschler E, Wess J (1994) Identification of an intracellular tyrosine residue critical for muscarinic receptor-mediated stimulation of phosphatidylinositol hydrolysis. J Biol Chem 269:402–5

    PubMed  Google Scholar 

  • Bond C, LaForge KS, Tian M, Melia D, Zhang S, Borg L, Gong J, Schluger J, Strong JA, Leal SM, Tischfield JA, Kreek MJ, Yu L (1998) Single-nucleotide polymorphism in the human mu opioid receptor gene alters β-endorphin binding and activity: possible implications for opiate addiction. Proc Natl Acad Sci USA 95:9608–13

    PubMed  CAS  Google Scholar 

  • Bond RA, Leff P, Johnson TD, Milano CA, Rockman HA, McMinn TR, Apparsundaram S, Hyek MF, Kenakin TP, Allen LF (1995) Physiological effects of inverse agonists in transgenic mice with myocardial overexpression of the β2-adrenoceptor. Nature 374:272–6

    PubMed  CAS  Google Scholar 

  • Bouvier M, Chidiac P, Hebert TE, Loisel TP, Moffett S, Mouillac B (1995) Dynamic palmitoylation of G-protein-coupled receptors in eukaryotic cells. Methods Enzymol 250:300–14

    PubMed  CAS  Google Scholar 

  • Brand E, Bankir L, Plouin PF, Soubrier F (1999) Glucagon receptor gene mutation (Gly40Ser) in human essential hypertension: the PEGASE study. Hypertension 34:15–7

    PubMed  CAS  Google Scholar 

  • Brodde OE, Buscher R, Tellkamp R, Radke J, Dhein S, Insel PA (2001) Blunted cardiac responses to receptor activation in subjects with Thr164Ile β2-adrenoceptors. Circulation 103:1048–50

    PubMed  CAS  Google Scholar 

  • Brown CR, Hong-Brown LQ, Biwersi J, Verkman AS, Welch WJ (1996) Chemical chaperones correct the mutant phenotype of the ΔF508 cystic fibrosis transmembrane conductance regulator protein. Cell Stress Chaperones 1:117–25

    PubMed  CAS  Google Scholar 

  • Bunge S, Wedemann H, David D, Terwilliger DJ, van den Born LI, Aulehla-Scholz C, Samanns C, Horn M, Ott J, Schwinger E (1993) Molecular analysis and genetic mapping of the rhodopsin gene in families with autosomal dominant retinitis pigmentosa. Genomics 17:230–3

    PubMed  CAS  Google Scholar 

  • Burger M, Burger JA, Hoch RC, Oades Z, Takamori H, Schraufstatter IU (1999) Point mutation causing constitutive signaling of CXCR2 leads to transforming activity similar to Kaposi's sarcoma herpesvirus-G protein-coupled receptor. J Immunol 163:2017–22

    PubMed  CAS  Google Scholar 

  • Burns CM, Chu H, Rueter SM, Hutchinson LK, Canton H, Sanders-Bush E, Emeson RB (1997) Regulation of serotonin-2C receptor G-protein coupling by RNA editing. Nature 387:303–8

    PubMed  CAS  Google Scholar 

  • Busque L, Mio R, Mattioli J, Brais E, Blais N, Lalonde Y, Maragh M Gilliland DG (1996) Nonrandom X-inactivation patterns in normal females: Lyonization ratios vary with age. Blood 88:59–65

    PubMed  CAS  Google Scholar 

  • Cao TT, Deacon HW, Reczek D, Bretscher A, von Zastrow M (1999) A kinase-regulated PDZ-domain interaction controls endocytic sorting of the β2-adrenergic receptor. Nature 401:286–90

    PubMed  CAS  Google Scholar 

  • Castellano M, Muiesan ML, Beschi M, Rizzoni D, Cinelli A, Salvetti M, Pasini G, Porteri E, Bettoni G, Zulli R, Agabiti-Rosei E (1996) Angiotensin II type 1 receptor A/C1166 polymorphism. Relationships with blood pressure and cardiovascular structure. Hypertension 28:1076–80

    PubMed  CAS  Google Scholar 

  • Cetani F, Tonacchera M, Vassart G (1996) Differential effects of NaCl concentration on the constitutive activity of the thyrotropin and the luteinizing hormone/chorionic gonadotropin receptors. FEBS Lett 378:27–31

    PubMed  CAS  Google Scholar 

  • Chatterjee TK, Sharma RV, Fisher RA (1996) Molecular cloning of a novel variant of the pituitary adenylate cyclase-activating polypeptide (PACAP) receptor that stimulates calcium influx by activation of L-type calcium channels. J Biol Chem 271:32226–32

    PubMed  CAS  Google Scholar 

  • Chen, KS, Manian P, Koeuth T, Potocki L, Zhao Q, Chinault AC, Lee CC, Lupski JR (1997) Homologous recombination of a flanking repeat gene cluster is a mechanism for a common contiguous gene deletion syndrome. Nat Genet 17:154–63

    PubMed  CAS  Google Scholar 

  • Cheng SH, Gregory RJ, Marshall J, Paul S, Souza DW, White GA, O'Riordan CR, Smith AE (1990) Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis. Cell 63:827–34

    PubMed  CAS  Google Scholar 

  • Claeysen S, Sebben M, Becamel C, Bockaert J, Dumuis (1999) A Novel brain-specific 5-HT4 receptor splice variants show marked constitutive activity: role of the C-terminal intracellular domain. Mol Pharmacol 55:910–20

    PubMed  CAS  Google Scholar 

  • Clark AJ, McLoughlin L, Grossman A (1993) Familial glucocorticoid deficiency associated with point mutation in the adrenocorticotropin receptor. Lancet 341:461–2

    PubMed  CAS  Google Scholar 

  • Clegg AO, Ashton LJ, Biti RA, Badhwar P, Williamson P, Kaldor JM, Stewart GJ (2000) CCR5 promoter polymorphisms, CCR5 59029A and CCR5 59353C, are under represented in HIV-1-infected long-term non-progressors. The Australian Long-Term Non-Progressor Study Group. AIDS 14:103–8

    PubMed  CAS  Google Scholar 

  • Clifton-Bligh RJ, Gregory JW, Ludgate M, John R, Persani L, Asteria C, Beck-Peccoz P, Chatterjee VK (1997) Two novel mutations in the thyrotropin (TSH) receptor gene in a child with resistance to TSH. J Clin Endocrinol Metab 82:1094–100

    PubMed  CAS  Google Scholar 

  • Cole-Strauss A, Yoon K, Xiang Y, Byrne BC, Rice MC, Gryn J, Holloman WK, Kmiec EB (1996) Correction of the mutation responsible for sickle cell anemia by an RNA-DNA oligonucleotide. Science 273:1386–9

    PubMed  CAS  Google Scholar 

  • Colley NJ, Cassill JA, Baker EK, Zuker CS (1995) Defective intracellular transport is the molecular basis of rhodopsin-dependent dominant retinal degeneration. Proc Natl Acad Sci USA 92:3070–4

    PubMed  CAS  Google Scholar 

  • Collu R, Tang J, Castagne J, Lagace G, Masson N, Huot C, Deal C, Delvin E, Faccenda E, Eidne KA, Van Vliet G (1997) A novel mechanism for isolated central hypothyroidism: inactivating mutations in the thyrotropin-releasing hormone receptor gene. J Clin Endocrinol Metab 82:1561–5

    PubMed  CAS  Google Scholar 

  • Conn PM, Rogers DC, Stewart JM, Niedel J, Sheffield T (1982) Conversion of a gonadotropin-releasing hormone antagonist to an agonist. Nature 296:653–5

    PubMed  CAS  Google Scholar 

  • Cook JV, Eidne KA (1997) An intramolecular disulfide bond between conserved extracellular cysteines in the gonadotropin-releasing hormone receptor is essential for binding and activation. Endocrinology 138:2800–6

    PubMed  CAS  Google Scholar 

  • Cope DL, Holman GD, Baldwin SA, Wolstenholme AJ (1994) Domain assembly of the GLUT1 glucose transporter. Biochem J 300:291–4

    PubMed  CAS  Google Scholar 

  • Coward P, Wada HG, Falk MS, Chan SD, Meng F, Akil H, Conklin BR (1998) Controlling signaling with a specifically designed Gi-coupled receptor. Proc Natl Acad Sci USA 95:352–7

    PubMed  CAS  Google Scholar 

  • Cravchik A, Sibley DR, Gejman PV (1996) Functional analysis of the human D2 dopamine receptor missense variants. J Biol Chem 271:26013–7

    PubMed  CAS  Google Scholar 

  • Culbertson MR (1999) RNA surveillance. Unforeseen consequences for gene expression, inherited genetic disorders and cancer. Trends Genet 15:74–80

    PubMed  CAS  Google Scholar 

  • Daaka Y, Luttrell LM, Lefkowitz RJ (1997) Switching of the coupling of the α2-adrenergic receptor to different G proteins by protein kinase A. Nature 390:88–91

    PubMed  CAS  Google Scholar 

  • Danner S, Lohse MJ (1999) Regulation of beta-adrenergic receptor responsiveness modulation of receptor gene expression. Rev Physiol Biochem Pharmacol 136:183–223

    PubMed  CAS  Google Scholar 

  • de Herder WW, Krenning EP, Malchoff CD, Hofland LJ, Reubi JC, Kwekkeboom DJ, Oei HY, Pols HA, Bruining HA, Nobels FR (1994) Somatostatin receptor scintigraphy: its value in tumor localization in patients with Cushing's syndrome caused by ectopic corticotropin or corticotropin-releasing hormone secretion. Am J Med 96:305–12

    PubMed  Google Scholar 

  • de Roux N, Polak M, Couet J, Leger J, Czernichow P, Milgrom E, Misrahi M (1996) A neomutation of the thyroid-stimulating hormone receptor in a severe neonatal hyperthyroidism. J Clin Endocrinol Metab 81:2023–6

    PubMed  Google Scholar 

  • de Roux N, Young J, Brailly-Tabard S, Misrahi M, Milgrom E, Schaison G (1999) The same molecular defects of the gonadotropin-releasing hormone receptor determine a variable degree of hypogonadism in affected kindred. J Clin Endocrinol Metab 84:567–72

    PubMed  Google Scholar 

  • de Roux N, Young J, Misrahi M, Genet R, Chanson P, Schaison G, Milgrom E (1997) A family with hypogonadotropic hypogonadism and mutations in the gonadotropin-releasing hormone receptor. N Engl J Med 337:1597–602

    PubMed  Google Scholar 

  • Debouck C, Metcalf B (2000) The impact of genomics on drug discovery. Annu Rev Pharmacol Toxicol 40:193–207

    PubMed  CAS  Google Scholar 

  • DeCamp DL, Thompson TM, de Sauvage FJ, Lerner MR (2000) Smoothened activates Gαi mediated signaling in frog melanophores. J Biol Chem 275:26322–7

    PubMed  CAS  Google Scholar 

  • de Lean A, Stadel JM, Lefkowitz RJ (1980) A ternary complex model explains the agonist-specific binding properties of the adenylate cyclase-coupled β-adrenergic receptor. J Biol Chem 255:7108–17

    PubMed  Google Scholar 

  • Dhanasekaran N, Heasley LE, Johnson GL (1995) G protein-coupled receptor systems involved in cell growth and oncogenesis. Endocr Rev 16:259–70

    PubMed  CAS  Google Scholar 

  • Dryja TP, McGee TL, Reichel E, Hahn LB, Cowley GS, Yandell DW, Sandberg MA, Berson EL (1990) A point mutation of the rhodopsin gene in one form of retinitis pigmentosa. Nature 343:364–6

    PubMed  CAS  Google Scholar 

  • Duprez L, Parma J, Van Sande J, Allgeier A, Leclere J, Schvartz C, Delisle MJ, Decoulx M, Orgiazzi J, Dumont J, Vassart G (1994) Germline mutations in the thyrotropin receptor gene cause non-autoimmune autosomal dominant hyperthyroidism. Nat Genet 7:396–401

    PubMed  CAS  Google Scholar 

  • Ebisawa T, Kajimura N, Uchiyama M, Katoh M, Sekimoto M, Watanabe T, Ozeki Y, Ikeda M, Jodoi T, Sugishita M, Iwase T, Kamei Y, Kim K, Shibui K, Kudo Y, Yamada N, Toyoshima R, Okawa M, Takahashi K, Yamauchi T (1999) Alleic variants of human melatonin 1a receptor: function and prevalence in subjects with circadian rhythm sleep disorders. Biochem Biophys Res Commun 262:832–7

    PubMed  CAS  Google Scholar 

  • Ebisawa T, Uchiyama M, Kajimura N, Kamei Y, Shibui K, Kim K, Kudo Y, Iwase T, Sugishita M, Jodoi T, Ikeda M, Ozeki Y, Watanabe T, Sekimoto M, Katoh M, Ya-mada N, Toyoshima R, Okawa M, Takahashi K, Yamauchi T (2000) Genetic polymorphisms of human melatonin 1b receptor gene in circadian rhythm sleep disorders and controls. Neurosci Lett 280:29–32

    PubMed  CAS  Google Scholar 

  • Elling CE, Nielsen SM, Schwartz TW (1995) Conversion of antagonist-binding site to metal-ion site in the tachykinin NK-1 receptor. Nature 374:74–7

    PubMed  CAS  Google Scholar 

  • Erbel PJ, Karimi-Nejad Y, De Beer T, Boelens R, Kamerling JP, Vliegenthart JF (1999) Solution structure of the a-subunit of human chorinoic gonadotropin. Eur J Biochem 260:490–8

    PubMed  CAS  Google Scholar 

  • Erlenbach I, Wess J (1998) Molecular basis of V2 vasopressin receptor/G3 coupling selectivity. J Biol Chem 273:26549–58

    PubMed  CAS  Google Scholar 

  • Farahbakhsh ZT, Ridge KD, Khorana HG, Hubbell WL (1995) Mapping light-dependent structural changes in the cytoplasmic loop connecting helices C and D in rhodopsin: a site-directed spin labeling study. Biochemistry 34:8812–9

    PubMed  CAS  Google Scholar 

  • Farooqi IS, Yeo GS, Keogh JM, Aminian S, Jebb SA, Butler G, Cheetham T, O'Rahilly S (2000) Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency. J Clin Invest 106:271–9

    PubMed  CAS  Google Scholar 

  • Farrens DL, Altenbach C, Yang K, Hubbell WL, Khorana HG (1996) Requirement of rigid-body motion of transmembrane helices for light activation of rhodopsin. Science 274:768–70

    PubMed  CAS  Google Scholar 

  • Faure S, Meyer L, Costagliola D, Vaneensberghe C, Genin E, Autran B, Delfraissy JF, McDermott DH, Murphy PM, Debre P, Theodorou I, Combadiere C (2000) Rapid progression to AIDS in HIV+individuals with a structural variant of the chemokine receptor CX3CR1. Science 287:2274–7

    PubMed  CAS  Google Scholar 

  • Feng J, Zheng J, Gelernter J, Kranzler H, Cook E, Goldman D, Jones IR, Craddock N, Heston LL, Delisi L, Peltonen L, Bennett WP, Sommer SS (2001) An in-frame deletion in the α2C adrenergic receptor is common in African-Americans. Mol Psychiatry 6:168–72

    PubMed  CAS  Google Scholar 

  • Ferreira PA, Nakayama TA, Pak WL, Travis GH (1996) Cyclophilin-related protein RanBP2 acts as a chaperone for red/green opsin. Nature 383:637–40

    PubMed  CAS  Google Scholar 

  • Ferrero GB, Gebbia M, Pilia G, Witte D, Peier A, Hopkin RJ, Craigen WJ, Shaffer LG, Schlessinger D, Ballabio A, Casey B (1997) A submicroscopic deletion in Xq26 associated with familial situs ambiguus. Am J Hum Genet 61:395–401

    PubMed  CAS  Google Scholar 

  • Ferris HA, Carroll RE, Rasenick MM, Benya RV (1997) Constitutive activation of the gastrin-releasing peptide receptor expressed by the nonmalignant human colon epithelial cell line NCM460. J Clin Invest 100:2530–7

    PubMed  CAS  Google Scholar 

  • Franke RR, Sakmar TP, Graham RM, Khorana HG (1992) Structure and function in rhodopsin. Studies of the interaction between the rhodopsin cytoplasmic domain and transducin. J Biol Chem 267:14767–74

    PubMed  CAS  Google Scholar 

  • Fries MH, Lebo RV, Schonberg SA, Golabi M, Seltzer WK, Gitelman SE, Golbus MS (1993) Mental retardation locus in Xp21 chromosome microdeletion. Am J Med Genet 46:363–8

    PubMed  CAS  Google Scholar 

  • Fuchs S, Amiel J, Claudel S, Lyonnet S, Corvol P, Pinet F (2001) Functional characterization of three mutations of the endothelin B receptor gene in patients with Hirschsprung's disease: evidence for selective loss of Gi coupling. Mol Med 7:115–24

    PubMed  CAS  Google Scholar 

  • Fuchs S, Kranich H, Denton MJ, Zrenner E, Bhattacharya SS, Humphries P, Gal A (1994) Three novel rhodopsin mutations (C110F, L131P, A164V) in patients with autosomal dominant retinitis pigmentosa. Hum Mol Genet 3:1203

    PubMed  CAS  Google Scholar 

  • Fujiwara TM, Morgan K, Bichet DG (1995) Molecular biology of diabetes insipidus. Annu Rev Med 46:331–43

    PubMed  CAS  Google Scholar 

  • Gagne N, Parma J, Deal C, Vassart G, Van Vliet G (1998) Apparent congenital athyreosis contrasting with normal plasma thyroglobulin levels and associated with inactivating mutations in the thyrotropin receptor gene: are athyreosis and ectopic thyroid distinct entities?. J Clin Endocrinol Metab 83:1771–5

    PubMed  CAS  Google Scholar 

  • Gales C, Kowalski-Chauvel A, Dufour MN, Seva C, Moroder L, Pradayrol L, Vaysse N, Fourmy D, Silvente-Poirot S (2000) Mutation of Asn-391 within the conserved NPXXY motif of the cholecystokinin B receptor abolishes Gq protein activation without affecting its association with the receptor. J Biol Chem 275:17321–7

    PubMed  CAS  Google Scholar 

  • Gedeon AK, Meinanen M, Ades LC, Kaariainen H, Gecz J, Baker E, Sutherland GR, Mulley JC (1995) Overlapping submicroscopic deletions in Xq28 in two unrelated boys with developmental disorders: identification of a gene near FRAXE. Am J Hum Genet 56:907–14

    PubMed  CAS  Google Scholar 

  • George SR, Fan T, Xie Z, Tse R, Tam V, Varghese G, O'Dowd BF Oligomerization of μ-and κ-opioid receptors. Generation of novel functional properties. J Biol Chem 275:26128–35

    Google Scholar 

  • George SR, Lee SP, Varghese G, Zeman PR, Seeman P, Ng GY, O'Dowd BF (1998) A transmembrane domain-derived peptide inhibits D1 dopamine receptor function without affecting receptor oligomerization. J Biol Chem 273:30244–8

    PubMed  CAS  Google Scholar 

  • Geras-Raaka E, Varma A, Ho H, Clark-Lewis I, Gershengorn MC (1998a) Human interferon-gamma-inducible protien 10 (IP-10) inhibits constitutive signaling of Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor. J Exp Med 188:405–8

    PubMed  CAS  Google Scholar 

  • Geras-Raaka E, Arvanitakis L, Bais C, Cesarman E, Mesri EA, Gershengorn MC (1998b) Inhibition of constitutive signaling of Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor by protein kinases in mammalian cells in culture. J Exp Med 187:801–6

    PubMed  CAS  Google Scholar 

  • Gether U, Lin S, Ghanouni P, Ballesteros JA, Weinstein H, Kobilka BK (1997) Agonists induce conformational changes in transmembrane domains III and VI of the β2 adrenoceptor. EMBO J 16:6737–47

    PubMed  CAS  Google Scholar 

  • Gether U, Lin S, Kobilka BK (1995) Fluorescent labeling of purified β2 adrenergic receptor. Evidence for ligand-specific conformational changes. J Biol Chem 270:28268–75

    PubMed  CAS  Google Scholar 

  • Ghanouni P, Steenhuis JJ, Farrens DL, Kobilka BK (2001) Agonist-induced conformational changes in the G-protein-coupling domain of the beta 2 adrenergic receptor. Proc Natl Acad Sci USA 98:5997–6002

    PubMed  CAS  Google Scholar 

  • Ghanouni P, Schambye H, Seifert R, Lee TW, Rasmussen SG, Gether U, Kobilka BK (2000) The effect of pH on β2 adrenoceptor function Evidence for protonation-dependent activation. J Biol Chem 275:3121–7

    PubMed  CAS  Google Scholar 

  • Gilad S, Khosravi R, Shkedy D, Uziel T, Ziv Y, Savitsky K, Rotman G, Smith S, Chessa L, Jorgensen TJ, Harnik R, Frydman M, Sanal O, Portnoi S, Goldwicz Z, Jaspers NG, Gatti RA, Lenoir G, Lavin MF, Tatsumi K, Wegner RD, Shiloh Y, Bar-Shira A (1996) Predominance of null mutations in ataxia-telangiectasia. Hum Mol Genet 5:433–9

    PubMed  CAS  Google Scholar 

  • Gilchrist RL, Ryu KS, Ji I, Ji TH (1996) The luteinizing hormone/chorionic gonadotropin receptor has distinct transmembrane conductors for cAMP and inositol phosphate signals. J Biol Chem 271:19283–7

    PubMed  CAS  Google Scholar 

  • Glusman G, Yanai I, Rubin I, Lancet D (2001) The complete human olfactory subgenome. Genome Res 11:685–702

    PubMed  CAS  Google Scholar 

  • Godfrey P, Rahal JO, Beamer WG, Copeland NG, Jenkins NA, Mayo KE (1993) GHRH receptor of little mice contains a missense mutation in the extracellular domain that disrupts receptor function. Nat Genet 4:227–32

    PubMed  CAS  Google Scholar 

  • Gouldson PR, Snell CR, Bywater RP, Higgs C, Reynolds CA (1998) Domain swapping in G-protein coupled receptor dimers. Protein Eng 11:1181–93

    PubMed  CAS  Google Scholar 

  • Green SA, Turki J, Innis M, Liggett SB (1994) Amino-terminal polymorphisms of the human beta 2-adrenergic receptor impart distinct agonist-promoted regulatory properties. Biochemistry 33:9414–9

    PubMed  CAS  Google Scholar 

  • Gromoll J, Eiholzer U, Nieschlag E, Simoni M (2000) Male hypogonadism caused by homozygous deletion of exon 10 of the luteinizing hormone (LH) receptor: differential action of human chorionic gonadotropin and LH. J Clin Endocrinol Metab 85:2281–6

    PubMed  CAS  Google Scholar 

  • Grosse R, Schöneberg T, Schultz G, Gudermann T (1997) Inhibition of gonadotropin-releasing hormone receptor signaling by expression of a splice variant of the human receptor. Mol Endocrinol 11:1305–18

    PubMed  CAS  Google Scholar 

  • Grossmann M, Leitolf H, Weintraub BD, Szkudlinski MW (1998) A rational design strategy for protein hormone superagonists. Nat Biotechnol 16:871–5

    PubMed  CAS  Google Scholar 

  • Grüters A, Krude H, Biebermann H, Liesenkotter KP, Schöneberg T, Gudermann T (1999) Alterations of neonatal thyroid function. Acta Paediatr Suppl 88:17–22

    PubMed  Google Scholar 

  • Grüters A, Schöneberg T, Biebermann H, Krude H, Krohn HP, Dralle H, Gudermann T (1998) Severe congenital hyperthyroidism caused by a germ-line neo mutation in the extracellular portion of the thyrotropin receptor. J Clin Endocrinol Metab 83:1431–6

    PubMed  Google Scholar 

  • Gudermann T, Schöneberg T, Schultz G (1997) Functional and structural complexity of signal transduction via G-protein-coupled receptors. Annu Rev Neurosci 20:399–427

    PubMed  CAS  Google Scholar 

  • Guiramand J, Montmayeur JP, Ceraline J, Bhatia M, Borrelli E (1995) Alternative splicing of the dopamine D2 receptor directs specificity of coupling to G-proteins. J Biol Chem 270:7354–8

    PubMed  CAS  Google Scholar 

  • Gutkind JS, Novotny EA, Brann MR, Robbins KC (1991) Muscarinic acetylcholine receptor subtypes as agonist-dependent oncogenes. Proc Natl Acad Sci USA 88:4703–8

    PubMed  CAS  Google Scholar 

  • Hager J, Hansen L, Vaisse C, Vionnet N, Philippi A, Poller W, Velho G, Carcassi C, Contu L, Julier C (1995) A missense mutation in the glucagon receptor gene is associated with non-insulin-dependent diabetes mellitus. Nat Genet 9:299–304

    PubMed  CAS  Google Scholar 

  • Hall RA, Premont RT, Chow CW, Blitzer JT, Pitcher JA, Claing A, Stoffel RH, Barak LS, Shenolikar S, Weinman EJ, Grinstein S, Lefkowitz RJ (1998) The β2-adrenergic receptor interacts with the Na+/H+-exchanger regulatory factor to control Na+/H+ exchange. Nature 392:626–30

    PubMed  CAS  Google Scholar 

  • Hall RA, Premont RT, Lefkowitz RJ (1999) Heptahelical receptor signaling: beyond the G protein paradigm. J Cell Biol 145:927–32

    PubMed  CAS  Google Scholar 

  • Hamm HE (1998) The many faces of G protein signaling. J Biol Chem 273:669–72

    PubMed  CAS  Google Scholar 

  • Hani EH, Dupont S, Durand E, Dina C, Gallina S, Gantz I, Froguel P (2001) Naturally occurring mutations in the melanocortin receptor 3 gene are not associated with type 2 diabetes mellitus in French Caucasians. J Clin Endocrinol Metab 86:2895–8

    PubMed  CAS  Google Scholar 

  • Harteveld KL, Losekoot M, Fodde R, Giordano PC, Bernini LF (1997) The involvement of Alu repeats in recombination events at the α-globin gene cluster: characterization of two α°-thalassaemia deletion breakpoints. Hum Genet 99:528–34

    PubMed  CAS  Google Scholar 

  • Hatta N, Dixon C, Ray AJ, Phillips SR, Cunliffe WJ, Dale M, Todd C, Meggit S, BirchMacHin MA, Rees JL (2001) Expression, candidate gene, and population studies of the melanocortin 5 receptor. J Invest Dermatol 116:564–70

    PubMed  CAS  Google Scholar 

  • Hausdorff WP, Caron MG, Lefkowitz RJ (1990) Turning off the signal: desensitization of β-adrenergic receptor function. FASEB J 4:2881–9

    PubMed  CAS  Google Scholar 

  • Hayes JS, Lawler OA, Walsh MT, Kinsella BT (1999) The prostacyclin receptor is isoprenylated. Isoprenylation is required for efficient receptor-effector coupling. J Biol Chem 274:23707–18

    PubMed  CAS  Google Scholar 

  • Heard E, Clerc P, Avner P (1997) X-chromosome inactivation in mammals. Annu Rev Genet 31:571–610

    PubMed  CAS  Google Scholar 

  • Hebert TE, Moffett S, Morello JP, Loisel TP, Bichet DG, Barret C, Bouvier M (1996) A peptide derived from a β2-adrenergic receptor transmembrane domain inhibits both receptor dimerization and activation. J Biol Chem 271:16384–92

    PubMed  CAS  Google Scholar 

  • Heinflink M, Nussenzveig DR, Grimberg H, Lupu-Meiri M, Oron Y, Gershengorn MC (1995) A constitutively active mutant thyrotropin-releasing hormone receptor is chronically down-regulated in pituitary cells: evidence using chlordiazepoxide as a negative antagonist. Mol Endocrinol 9:1455–60

    PubMed  CAS  Google Scholar 

  • Heinonen P, Koulu M, Pesonen U, Karvonen MK, Rissanen A, Laakso M, Valve R, Uusitupa M, Scheinin M (1999) Identification of a three-amino acid deletion in the α2B-adrenergic receptor that is associated with reduced basal metabolic rate in obese subjects. J Clin Endocrinol Metab 84:2429–33

    PubMed  CAS  Google Scholar 

  • Heisler LK, Chu HM, Brennan TJ, Danao JA, Bajwa P, Parsons LH, Tecott LH (1998) Elevated anxiety and antidepressant-like responses in serotonin 5-HT1A receptor mutant mice. Proc Natl Acad Sci USA 95:15049–54

    PubMed  CAS  Google Scholar 

  • Helmreich EJ, Hofmann KP (1996) Structure and function of proteins in G-protein-coupled signal transfer. Biochim Biophys Acta 1286:285–322

    PubMed  CAS  Google Scholar 

  • Heuss C, Gerber U (2000) G-protein-independent signaling by G-protein-coupled receptors. Trends Neurosci 23:469–75

    PubMed  CAS  Google Scholar 

  • Heymann JAW, Subramaniam S (1997) Expression, stability, and membrane integration of truncation mutants of bovine rhodopsin. Proc Natl Acad Sci USA 94:4966–71

    PubMed  CAS  Google Scholar 

  • Hipkin RW, Liu X, Ascoli M (1995) Truncation of the C-terminal tail of the follitropin receptor does not impair the agonist-or phorbol ester-induced receptor phosphorylation and uncoupling. J Biol Chem 270:26683–9

    PubMed  CAS  Google Scholar 

  • Hirata T, Kakizuka A, Ushikubi F, Fuse I, Okuma M, Narumiya S (1994) Arg60 to Leu mutation of the human thromboxane A2 receptor in a dominantly inherited bleeding disorder. J Clin Invest 94:1662–7

    PubMed  CAS  Google Scholar 

  • Ho HH, Du D, Gershengorn MC (1999) The N terminus of Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor is necessary for high affinity chemokine binding but not for constitutive activity. J Biol Chem 274:31327–32

    PubMed  CAS  Google Scholar 

  • Hoffmann C, Moro S, Nicholas RA, Harden TK, Jacobson KA (1999) The role of amino acids in extracellular loops of the human P2Y1 receptor in surface expression and activation processes. J Biol Chem 274:14639–47

    PubMed  CAS  Google Scholar 

  • Hollopeter G, Jantzen HM, Vincent D, Li G, England L, Ramakrishnan V, Yang RB, Nurden P, Nurden A, Julius D, Conley PB (2001) Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature 409:202–7

    PubMed  CAS  Google Scholar 

  • Hosoda K, Hammer RE, Richardson JA, Baynash AG, Cheung JC, Giaid A, Yanagisawa M (1994) Targeted and natural (piebald-lethal) mutations of endothelin-B receptor gene produce megacolon associated with spotted coat color in mice. Cell 79:1267–76

    PubMed  CAS  Google Scholar 

  • Hsu SY, Kudo M, Chen T, Nakabayashi K, Bhalla A, van der Spek PJ, van Duin M, Hsueh AJ (2000) The three subfamilies of leucine-rich repeat-containing G protein-coupled receptors (LGR): identification of LGR6 and LGR7 and the signaling mechanism for LGR7. Mol Endocrinol 14:1257–71

    PubMed  CAS  Google Scholar 

  • Hu LJ, Laporte J, Kress W, Kioschis P, Siebenhaar R, Poustka A, Fardeau M, Metzenberg A, Janssen EA, Thomas N, Mandel JL, Dahl N (1996) Deletions in Xq28 in two boys with myotubular myopathy and abnormal genital development define a new contiguous gene syndrome in a 430 kb region. Hum Mol Genet 5:139–43

    PubMed  CAS  Google Scholar 

  • Huang KS, Bayley H, Liao MJ, London E, Khorana HG (1981) Refolding of an integral membrane protein. Denaturation, renaturation, and reconstitution of intact bacteriorhodopsin and two proteolytic fragments. J Biol Chem 256:3802–9

    PubMed  CAS  Google Scholar 

  • Iida-Klein A, Guo J, Xie LY, Juppner H, Potts JT Jr, Kronenberg HM, Bringhurst FR, Abou-Samra AB, Segre GV (1995) Truncation of the carboxyl-terminal region of the rat parathyroid hormone (PTH)/PTH-related peptide receptor enhances PTH stimulation of adenylyl cyclase but not phospholipase C. J Biol Chem 270:8458–65

    PubMed  CAS  Google Scholar 

  • Iiri T, Bell SM, Baranski TJ, Fujita T, Bourne HRA (1999) G mutant designed inhibit receptor signaling through Gs. Proc Natl Acad Sci USA 96:499–504

    PubMed  CAS  Google Scholar 

  • Imamura F, Arimoto I, Fujiyoshi Y, Doi T (2000) W276 mutation in the endothelin receptor subtype B impairs Gq coupling but not Gi or Go coupling. Biochemistry 39:686–92

    PubMed  CAS  Google Scholar 

  • Innamorati G, Sadeghi H, Birnbaumer M (1996) A fully active nonglycosylated V2 vasopressin receptor. Mol Pharmacol 50:467–73

    PubMed  CAS  Google Scholar 

  • Inoue M, Hosoda K, Imura K, Kamata S, Fukuzawa M, Nakao K, Okada A (1998) Mutational analysis of the endothelin-B receptor gene in Japanese Hirschsprung's disease. J Pediatr Surg 33:1206–8

    PubMed  CAS  Google Scholar 

  • Ito M, Iwata N, Taniguchi T, Murayama T, Chihara K, Matsui T (1994) Functional characterization of two cholecystokinin-B/gastrin receptor isoforms: a preferential splice donor site in the human receptor gene. Cell Growth Differ 5:1127–35

    PubMed  CAS  Google Scholar 

  • Iwata N, Ozaki N, Inada T, Goldman D (2001) Association of a 5-HT5A receptor polymorphism, Pro15Ser, to schizophrenia. Mol Psychiatry 6:217–9

    PubMed  CAS  Google Scholar 

  • Jacobson SG, Kemp CM, Cideciyan AV, Macke JP, Sung CH, Nathans J (1994) Phenotypes of stop codon and splice site rhodopsin mutations causing retinitis pigmentosa. Invest Ophthalmol Vis Sci 35:2521–34

    PubMed  CAS  Google Scholar 

  • Janssens R, Paindavoine P, Parmentier M, Boeynaems JM (1999) Human P2Y2 receptor polymorphism: identification and pharmacological characterization of two allelic variants. Br J Pharmacol 127:709–16

    PubMed  CAS  Google Scholar 

  • Jaquette J, Segaloff DL (1997) Temperature sensitivity of some mutants of the lutropin/choriogonadotropin receptor. Endocrinology 138:85–91

    PubMed  CAS  Google Scholar 

  • Javitch JA, Fu D, Liapakis G, Chen J (1997) Constitutive activation of the β2 adrenergic receptor alters the orientation of its sixth membrane-spanning segment. J Biol Chem 272:18546–9

    PubMed  CAS  Google Scholar 

  • Jin J, Mao GF, Ashby B (1997) Constitutive activity of human prostaglandin E receptor EP3 isoforms. Br J Pharmacol 121:317–23

    PubMed  CAS  Google Scholar 

  • Jinnouchi H, Araki E, Miyamura N, Kishikawa H, Yoshimura R, Isami S, Yamaguchi K, Iwamatsu H, Shichiri M (1996) Analysis of vasopressin receptor type II (V2R) gene in three Japanese pedigrees with congenital nephrogenic diabetes insipidus: identification of a family with complete deletion of the V2R gene. Eur J Endocrinol 134:689–98

    PubMed  CAS  Google Scholar 

  • Jobert AS, Zhang P, Couvineau A, Bonaventure J, Roume J, Le Merrer M, Silve C (1998) Absence of functional receptors for parathyroid hormone and parathyroid hormone-related peptide in Blomstrand chondrodysplasia. J Clin Invest 102:34–40

    PubMed  CAS  Google Scholar 

  • Jones KA, Borowsky B, Tamm JA, Craig DA, Durkin MM, Dai M, Yao WJ, Johnson M, Gunwaldsen C, Huang LY, Tang C, Shen Q, Salon JA, Morse K, Laz T, Smith KE, Nagarathnam D, Noble SA, Branchek TA, Gerald C (1998) GABAB receptors function as a heteromeric assembly of the subunits GABABR1 and GABABR2. Nature 396:674–9

    PubMed  CAS  Google Scholar 

  • Jones PG, Curtis CAM, Hulme EC (1995) The function of a highly-conserved arginine residue in activation of the muscarinic M1 receptor. Eur J Pharmacol 288:251–7

    PubMed  CAS  Google Scholar 

  • Jordan BA, Devi LA (1999) G-protein-coupled receptor heterodimerization modulates receptor function. Nature 399:697–700

    PubMed  CAS  Google Scholar 

  • Ju H, Venema VJ, Marrero MB, Venema RC (1998) Inhibitory interactions of the bradykinin B2 receptor with endothelial nitric-oxide synthase. J Biol Chem 273:24025–9

    PubMed  CAS  Google Scholar 

  • Jung H, Windhaber R, Palm D, Schnackerz KD (1995) NMR and circular dichroism studies of synthetic peptides derived from the third intracellularloop of the β-adrenoceptor. FEBS Lett 358:133–6

    PubMed  CAS  Google Scholar 

  • Kahn TW, Engelman DM (1992) Bacteriorhodopsin can be refolded from two independently stable transmembrane helices and the complementary five-helix fragment. Biochemistry 31:6144–51

    PubMed  CAS  Google Scholar 

  • Kaupmann K, Malitschek B, Schuler V, Heid J, Froestl W, Beck P, Mosbacher J, Bischoff S, Kulik A, Shigemoto R, Karschin A, Bettler B (1998) GABAB-receptor subtypes assemble into functional heteromeric complexes. Nature 396:683–7

    PubMed  CAS  Google Scholar 

  • Kiel S, Bruss M, Bonisch H, Gothert M (2000) Pharmacological properties of the naturally occurring Phe-124-Cys variant of the human 5-HT1B receptor: changes in ligand binding, G-protein coupling and second messenger formation. Pharmacogenetics 10:655–66

    PubMed  CAS  Google Scholar 

  • Kilpatrick GJ, Dautzenberg FM, Martin GR, Eglen RM (1999) 7TM receptors: the splicing on the cake. Trends Pharmacol Sci 20:294–301

    PubMed  CAS  Google Scholar 

  • Klein C, Brin MF, Kramer P, Sena-Esteves M, de Leon D, Doheny D, Bressman S, Fahn S, Breakefield XO, Ozelius LJ (1999) Association of a missense change in the D2 dopamine receptor with myoclonus dystonia. Proc Natl Acad Sci USA 96:5173–6

    PubMed  CAS  Google Scholar 

  • Klein U, Ramirez MT, Kobilka BK, von Zastrow M (1997) A novel interaction between adrenergic receptors and the a-subunit of eukaryotic initiation factor 2B. J Biol Chem 272:19099–102

    PubMed  CAS  Google Scholar 

  • Kobilka BK, Kobilka TS, Daniel K, Regan JW, Caron MG, Lefkowitz RJ (1988) Chimeric α2-,β2-adrenergic receptors: delineation of domains involved in effector coupling and ligand binding specificity. Science 240:1310–6

    PubMed  CAS  Google Scholar 

  • Koivisto UM, Palvimo JJ, Janne OA, Kontula K (1994) A single-base substitution in the proximal Sp1 site of the human low density lipoprotein receptor promoter as a cause of heterozygous familial hypercholesterolemia. Proc Natl Acad Sci USA 91:10526–30

    PubMed  CAS  Google Scholar 

  • Kolbe M, Besir H, Essen LO, Oesterhelt D (2000) Structure of the light-driven chloride pump halorhodopsin at 1.8 Å resolution. Science 288:1390–6

    PubMed  CAS  Google Scholar 

  • Kopin AS, McBride EW, Gordon MC, Quinn SM, Beinborn M (1997) Inter-and intraspecies polymorphisms in the cholecystokinin-B/gastrin receptor alter drug efficacy. Proc Natl Acad Sci USA 94:11043–8

    PubMed  CAS  Google Scholar 

  • Kopito RR (1999) Biosynthesis and degradation of CFTR. Physiol Rev 79:S167–73

    PubMed  CAS  Google Scholar 

  • Kopp, P, van Sande J, Parma J, Duprez L, Gerber H, Joss E, Jameson JL, Dumont JE, Vassart G (1995) Brief report: congenital hyperthyroidism caused by a mutation in the thyrotropin-receptor gene. N Engl J Med 332:150–4

    PubMed  CAS  Google Scholar 

  • Kosugi S, Ban T, Akamizu T, Kohn LD (1992) Role of cysteine residues in the extracellular domain and exoplasmic loops of the transmembrane domain of the TSH receptor: effect of mutation to serine on TSH receptor activity and response to thyroid stimulating autoantibodies. Biochem Biophys Res Commun 189:1754–62

    PubMed  CAS  Google Scholar 

  • Kremer H, Kraaij R, Toledo SP, Post M, Fridman JB, Hayashida CY, van Reen M, Milgrom E, Ropers HH, Mariman E (1995) Male pseudohermaphroditism due to a homozygous missense mutation of the luteinizing hormone receptor gene. Nat Genet 9:160–4

    PubMed  CAS  Google Scholar 

  • Kroeger KM, Hanyaloglu AC, Seeber RM, Miles LE, Eidne KA (2001) Constitutive and agonist-dependent homo-oligomerization of the thyrotropin-releasing hormone receptor. Detection in living cells using bioluminescence resonance energy transfer. J Biol Chem 276:12736–43

    PubMed  CAS  Google Scholar 

  • Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, Kumasaka T, Nakanishi S, Jingami H, Morikawa K (2000) Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor. Nature 407:971–7

    PubMed  CAS  Google Scholar 

  • Laporte J, Biancalana V, Tanner SM, Kress W, Schneider V, Wallgren-Pettersson C, Herger F, Buj-Bello A, Blondeau F, Liechti-Gallati S, Mandel JL (2000) MTM1 mutations in X-linked myotubular myopathy. Hum Mutat 15:393–409

    PubMed  CAS  Google Scholar 

  • Lappalainen J, Zhang L, Dean M, Oz M, Ozaki N, Yu DH, Virkkunen M, Weight F, Linnoila M, Goldman D (1995) Identification, expression, and pharmacology of a Cys23-Ser23 substitution in the human 5-HT2C receptor gene (HTR2C). Genomics 27:274–9

    PubMed  CAS  Google Scholar 

  • Laue LL, Wu SM, Kudo M, Bourdony CJ, Cutler GB Jr, Hsueh AJ, Chan WY (1996) Compound heterozygous mutations of the luteinizing hormone receptor gene in Leydig cell hypoplasia. Mol Endocrinol 10:987–97

    PubMed  CAS  Google Scholar 

  • Laugwitz KL, Ungerer M, Schöneberg T, Weig HJ, Kronsbein K, Moretti A, Hoffmann K, Seyfarth M, Schultz G, Schömig A (1999) Adenoviral gene transfer of the human V2 vasopressin receptor improves contractile force of rat cardiomyocytes. Circulation 99:925–33

    PubMed  CAS  Google Scholar 

  • Lawler OA, Miggin SM, Kinsella BT (2001) Protein kinase A mediated phosphorylation of serine 357 of the mouse prostacyclin receptor regulates its coupling to Gs-, to Gi-and to Gq-coupled effector signaling. J Biol Chem 276:33596–607

    PubMed  CAS  Google Scholar 

  • Layman LC, Cohen DP, Jin M, Xie J, Li Z, Reindollar RH, Bolbolan S, Bick DP, Sherins RR, Duck LW, Musgrove LC, Sellers JC, Neill JD (1998) Mutations in gonadotropin-releasing hormone receptor gene cause hypogonadotropic hypogonadism. Nat Genet 18:14–5

    PubMed  CAS  Google Scholar 

  • Le Gouill C, Parent JL, Rola-Pleszczynski M, Stankova J (1997) Role of the Cys90, Cys95 and Cys173 residues in the structure and function of the human platelet-activating factor receptor. FEBS Lett 402:203–8

    PubMed  Google Scholar 

  • Le Gouill C, Parent JL, Caron CA, Gaudreau R, Volkov L, Rola-Pleszczynski M, Stankova J (1999) Selective modulation of wild type receptor functions by mutants of G-protein-coupled receptors. J Biol Chem 274:12548–54

    PubMed  Google Scholar 

  • Leavitt LM, Macaluso CR, Kim KS, Martin NP, Dumont ME (1999) Dominant negative mutations in the a-factor receptor, a G protein-coupled receptor encoded by the STE2 gene of the yeast Saccharomyces cerevisiae. Mol Gen Genet 261:917–32

    PubMed  CAS  Google Scholar 

  • Lee SP, O'Dowd BF, Ng GY, Varghese G, Akil H, Mansour A, Nguyen T, George SR (2000) Inhibition of cell surface expression by mutant receptors demonstrates that D2 dopamine receptors exist as oligomers in the cell. Mol Pharmacol 58:120–8

    PubMed  CAS  Google Scholar 

  • Lee TW, Cotecchia S, Milligan G (1997) Up-regulation of the levels of expression and function of a constitutively active mutant of the hamster α1B-adrenoceptor by ligands that act as inverse agonists. Biochem J 325:733–9

    PubMed  CAS  Google Scholar 

  • Lefkowitz RJ, Cotecchia S, Samama P, Costa T (1993) Constitutive activity of receptors coupled to guanine nucleotide regulatory proteins. Trends Pharmacol Sci 14:303–7

    PubMed  CAS  Google Scholar 

  • Li S, Liu X, Ascoli M (2000) p38JAB1 binds to the intracellular precursor of the lutropin/choriogonadotropin receptor and promotes its degradation. J Biol Chem 275:13386–93

    PubMed  CAS  Google Scholar 

  • Lin L, Faraco J, Li R, Kadotani H, Rogers W, Lin X, Qiu X, de Jong PJ, Nishino S, Mignot E (1999) The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell 98:365–76

    PubMed  CAS  Google Scholar 

  • Lin SC, Lin CR, Gukovsky I, Lusis AJ, Sawchenko PE, Rosenfeld MG (1993) Molecular basis of the little mouse phenotype and implications for cell type-specific growth. Nature 364:208–13

    PubMed  CAS  Google Scholar 

  • Lin Z, Shenker A, Pearlstein R (1997) A model of the lutropin/choriogonadotropin receptor: insights into the structural and functional effects of constitutively activating mutations. Protein Eng 10:501–10

    PubMed  CAS  Google Scholar 

  • Liu F, Wan Q, Pristupa ZB, Yu XM, Wang YT, Niznik HB (2000) Direct protein-protein coupling enables cross-talk between dopamine D5 and gamma-aminobutyric acid A receptors. Nature 403:274–80

    PubMed  CAS  Google Scholar 

  • Liu T, DeCostanzo AJ, Liu X, Wang Hy, Hallagan S, Moon RT, Malbon CC (2001) G protein signaling from activated rat frizzled-1 to the beta-catenin-Lef-Tcf pathway. Science 292:1718–22

    PubMed  CAS  Google Scholar 

  • Liu G, Duranteau L, Carel JC, Monroe J, Doyle DA, Shenker A (1999) Leydig-cell tumors caused by an activating mutation of the gene encoding the luteinizing hormone receptor. N Engl J Med 341:1731–6

    PubMed  CAS  Google Scholar 

  • Liu IS, Seeman P, Sanyal S, Ulpian C, Rodgers-Johnson PE, Serjeant GR, Van Tol HH (1996) Dopamine D4 receptor variant in Africans, D4valine194glycine is insensitive to dopamine and clozapine: report of a homozygous individual. Am J Med Genet 61:277–82

    PubMed  CAS  Google Scholar 

  • Liu IS, Kusumi I, Ulpian C, Tallerico T, Seeman P (1998) A serotonin-4 receptor-like pseudogene in humans. Brain Res Mol Brain Res 53:98–103

    PubMed  CAS  Google Scholar 

  • Liu J, Schöneberg T, van Rhee M, Wess J (1995) Mutational analysis of the relative orientation of transmembrane helices I and VII in G protein-coupled receptors. J Biol Chem 270:19532–9

    PubMed  CAS  Google Scholar 

  • Liu J, Wess J (1996) Different single receptor domains determine the distinct G protein coupling profiles of members of the vasopressin receptor family. J Biol Chem 271:8772–8

    PubMed  CAS  Google Scholar 

  • Liu R, Paxton WA, Choe S, Ceradini D, Martin SR, Horuk R, MacDonald ME, Stuhlmann H, Koup RA, Landau NR (1996) Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 86:367–77

    PubMed  CAS  Google Scholar 

  • Liu T, DeCostanzo AJ, Liu X, Wang Hy, Hallagan S, Moon RT, Malbon CC (2001) G protein signaling from activated rat frizzled-1 to the ß-catenin-Lef-Tcf pathway. Science 292:1718–22

    PubMed  CAS  Google Scholar 

  • Lohmann DR (1999) RB1 gene mutations in retinoblastoma. Hum Mutat 14:283–8

    PubMed  CAS  Google Scholar 

  • Lu D, Vage DI, Cone RD (1998) A ligand-mimetic model for constitutive activation of the melanocortin-1 receptor. Mol Endocrinol 12:592–604

    PubMed  CAS  Google Scholar 

  • Luecke H, Schobert B, Richter HT, Cartailler JP, Lanyi JK (1999) Structure of bacteriorhodopsin at 1.55 Å resolution. J Mol Biol 291:899–911

    PubMed  CAS  Google Scholar 

  • Luzius H, Jans DA, Grunbaum EG, Moritz A, Rascher W, Fahrenholz F (1992) A low affinity vasopressin V2-receptor in inherited nephrogenic diabetes insipidus. J Recept Res 12:351–68

    PubMed  CAS  Google Scholar 

  • Macke JP, Davenport CM, Jacobson SG, Hennessey JC, Gonzalez-Fernandez F, Conway BP, Heckenlively J, Palmer R, Maumenee IH, Sieving P (1993) Identification of novel rhodopsin mutations responsible for retinitis pigmentosa: implications for the structure and function of rhodopsin. Am J Hum Genet 53:80–9

    PubMed  CAS  Google Scholar 

  • Maggio R, Vogel Z, Wess J (1993) Co-expression studies with mutant muscarinic/adrenergic receptors provide evidence for intermolecular crosstalk between G protein-linked receptors. Proc Natl Acad Sci USA 90:3103–7

    PubMed  CAS  Google Scholar 

  • Manivet P, Mouillet-Richard S, Callebert J, Nebigil CG, Maroteaux L, Hosoda S, Kellermann O, Launay JM (2000) PDZ-dependent activation of nitric-oxide synthases by the serotonin 2B receptor. J Biol Chem 275:9324–31

    PubMed  CAS  Google Scholar 

  • Marchese A, Nguyen T, Malik P, Xu S, Cheng R, Xie Z, Heng HH, George SR, Kolakowski LF Jr, O'Dowd BF (1998) Cloning genes encoding receptors related to chemoattractant receptors. Genomics 50:281–6

    PubMed  CAS  Google Scholar 

  • Margeta-Mitrovic M, Jan YN, Jan LY (2000) A trafficking checkpoint controls GABAB receptor heterodimerization. Neuron 27:97–106

    PubMed  CAS  Google Scholar 

  • Marie J, Koch C, Pruneau D, Paquet JL, Groblewski T, Larguier R, Lombard C, Deslauriers B, Maigret B, Bonnafous JC (1999) Constitutive activation of the human bradykinin B2 receptor induced by mutations in transmembrane helices III and VI. Mol Pharmacol 55:92–101

    PubMed  CAS  Google Scholar 

  • Martin MM, Wu SM, Martin AL, Rennert OM, Chan WY (1998) Testicular seminoma in a patient with a constitutively activating mutation of the luteinizing hormone/chorionic gonadotropin receptor. Eur J Endocrinol 139:101–6

    PubMed  CAS  Google Scholar 

  • Mason DA, Moore JD, Green SA, Liggett SB (1999) A gain-of-function polymorphism in a G-protein coupling domain of the human β1-adrenergic receptor. J Biol Chem 274:12670–4

    PubMed  CAS  Google Scholar 

  • McLatchie LM, Fraser NJ, Main MJ, Wise A, Brown J, Thompson N, Solari R, Lee MG, Foord SM (1998) RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature 393:333–9

    PubMed  CAS  Google Scholar 

  • Milligan G, Bond RA (1997) Inverse agonism and the regulation of receptor number. Trends Pharmacol Sci 18:468–74

    PubMed  CAS  Google Scholar 

  • Milligan G, Bond RA, Lee M (1995) Inverse agonism: pharmacological curiosity or potential therapeutic strategy? Trends Pharmacol Sci 16:10–3

    PubMed  CAS  Google Scholar 

  • Misrahi M, Meduri G, Pissard S, Bouvattier C, Beau I, Loosfelt H, Jolivet A, Rappaport R, Milgrom E, Bougneres P (1997) Comparison of immunocytochemical and molecular features with the phenotype in a case of incomplete male pseudohermaphroditism associated with a mutation of the luteinizing hormone receptor. J Clin Endocrinol Metab 82:2159–65

    PubMed  CAS  Google Scholar 

  • Morello JP, Salahpour A, Laperriere A, Bernier V, Arthus MF, Lonergan M, Petaja-Repo U, Angers S, Morin D, Bichet DG, Bouvier M (2000) Pharmacological chaperones rescue cell-surface expression and function of misfolded V2 vasopressin receptor mutants. J Clin Invest 105:887–95

    PubMed  CAS  Google Scholar 

  • Morello JP, Salahpour A, Petaja-Repo UE, Laperriere A, Lonergan M, Arthus MF, Nabi IR, Bichet DG, Bouvier M (2001) Association of calnexin with wild type and mutant AVPR2 that cause nephrogenic diabetes insipidus. Biochemistry 40:6766–75

    PubMed  CAS  Google Scholar 

  • Morimura H, Saindelle-Ribeaudeau F, Berson EL, Dryja TP 1999 Mutations in RGR, encoding a light-sensitive opsin homologue, in patients with retinitis pigmentosa. Nat Genet 23:393–4

    PubMed  CAS  Google Scholar 

  • Moses AM, Sangani G, Miller JL (1995) Proposed cause of marked vasopressin resistance in a female with an X-linked recessive V2 receptor abnormality. J Clin Endocrinol Metab 80:1184–6

    PubMed  CAS  Google Scholar 

  • Mullikin JC, Hunt SE, Cole CG, Mortimore BJ, Rice CM, Burton J, Matthews LH, Pavitt R, Plumb RW, Sims SK, Ainscough RM, Attwood J, Bailey JM, Barlow K, Bruskiewich RM, Butcher PN, Carter NP, Chen Y, Clee CM, Coggill PC, Davies J, Davies RM, Dawson E, Francis MD, Joy AA, Lamble RG, Langford CF, Macarthy J, Mall V, Moreland A, Overton-Larty EK, Ross MT, Smith LC, Steward CA, Sulston JE, Tinsley EJ, Turney KJ, Willey DL, Wilson GD, McMurray AA, Dunham I, Rogers J, Bentley DR (2000) An SNP map of human chromosome 22, Nature 407:516–20.

    PubMed  CAS  Google Scholar 

  • Nagase T, Seki N, Tanaka A, Ishikawa K, Nomura N (1995) Prediction of the coding sequences of unidentified human genes. IV. The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of cDNA clones from human cell line KG-1. DNA Res 2:167–74

    PubMed  CAS  Google Scholar 

  • Nakagawa M, Miyamoto T, Kusakabe R, Takasaki S, Takao T, Shichida Y, Tsuda M (2001) O-Glycosylation of G-protein-coupled receptor, octopus rhodopsin. Direct analysis by FAB mass spectrometry. FEBS Lett 496:19–24

    PubMed  CAS  Google Scholar 

  • Namba T, Sugimoto Y, Negishi M, Irie A, Ushikubi F, Kakizuka, A, Ito S, Ichikawa A, Narumiya S (1993) Alternative splicing of C-terminal tail of prostaglandin E receptor subtype EP3 determines G-protein specificity. Nature 365:166–70

    PubMed  CAS  Google Scholar 

  • Nathans J, Hogness DS (1983) Isolation, sequence analysis, and intron-exon arrangement of the gene encoding bovine rhodopsin. Cell 34:807–14

    PubMed  CAS  Google Scholar 

  • Naville D, Barjhoux L, Jaillard C, Faury D, Despert F, Esteva B, Durand P, Saez JM, Begeot M (1996) Demonstration by transfection studies that mutations in the adrenocorticotropin receptor gene are one cause of the hereditary syndrome of glucocorticoid deficiency. J Clin Endocrinol Metab 81:1442–8

    PubMed  CAS  Google Scholar 

  • Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJP, Zuker CS (2001) Mammalian sweet taste receptors. Cell 106: 381–90

    PubMed  CAS  Google Scholar 

  • Nielsen SM, Elling CE, Schwartz TW (1998) Split-receptors in the tachykinin neurokinin-1 system—mutational analysis of intracellular loop 3. Eur J Biochem 251:217–26

    PubMed  CAS  Google Scholar 

  • Nijenhuis WA, Oosterom J, Adan RA (2001) AgRP (83-132) acts as an inverse agonist on the human-melanocortin-4-receptor. Mol Endocrinol 15:164–71

    PubMed  CAS  Google Scholar 

  • Nimchinsky EA, Hof Pr, Janssen WGM, Morrison JH, Schmauss C (1997) Expression of dopamine D3 receptor dimers and tetramers in brain and in transfected cells. J Biol Chem 272:29229–37

    PubMed  CAS  Google Scholar 

  • Niswender CM, Copeland SC, Herrick-Davis K, Emeson RB, Sanders-Bush E (1999) RNA editing of the human serotonin 5-hydroxytryptamine 2C receptor silences consitutive activity. J Biol Chem 274:9472–8

    PubMed  CAS  Google Scholar 

  • Nomura Y, Onigata K, Nagashima T, Yutani S, Mochizuki H, Nagashima K, Morikawa A (1997) Detection of skewed X-inactivation in two female carriers of vasopressin type 2 receptor gene mutation. J Clin Endocrinol Metab 82:3434–7

    PubMed  CAS  Google Scholar 

  • Nothen MM, Cichon S, Hemmer S, Hebebrand J, Remschmidt H, Lehmkuhl G, Poustka F, Schmidt M, Catalano M, Fimmers R (1994) Human dopamine D4 reptor gene: frequent occurrence of a null allele and observation of homozygosity. Hum Mol Genet 3:2207–12

    PubMed  CAS  Google Scholar 

  • Offermanns S (2000) Mammalian G-protein function in vivo: new insights through altered gene expression. Rev Physiol Biochem Pharmacol 140:63–133

    PubMed  CAS  Google Scholar 

  • Okuda-Ashitaka E, Sakamoto K, Ezashi T, Miwa K, Ito S, Hayaishi O (1996) Suppression of prostaglandin E receptor signaling by the variant form of EP1 subtype. J Biol Chem 271:31255–61

    PubMed  CAS  Google Scholar 

  • Oldenhof J, Vickery R, Anafi M, Oak J, Ray A, Schoots O, Pawson T, von Zastrow M, Van Tol HH (1998) SH3 binding domains in the dopamine D4 receptor. Biochemistry 37:15726–36

    PubMed  CAS  Google Scholar 

  • Okada T, Ernst OP, Palczewski K, Hofmann KP (2001) Activation of rhodopsin: new insights from structural and biochemical studies. Trends Biochem Sci 26:318–24

    PubMed  CAS  Google Scholar 

  • Oliveira SA, Shenk TE (2001) Murine cytomegalovirus M78 protein, a G proteincoupled receptor homologue, is a constituent of the virion and facilitates accumulation of immediate-early viral mRNA. Proc Natl Acad Sci USA 98:3237–42

    PubMed  CAS  Google Scholar 

  • Otaki JM, Firestein S (2001) Length analyses of mammalian g-protein-coupled receptors. J Theor Biol 211:77–100

    PubMed  CAS  Google Scholar 

  • Overton MC, Blumer KJ (2000) G-protein-coupled receptors function as oligomers in vivo. Curr Biol 10:341–4

    PubMed  CAS  Google Scholar 

  • Pagano A, Rovelli G, Mosbacher J et al. (2001) C-terminal interaction is essential for surface trafficking but not for heteromeric assembly of GABAB receptors. J Neuroscience 21:1189–202

    CAS  Google Scholar 

  • Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M (2000) Crystal structure of rhodopsin: A G protein-coupled receptor. Science 289:739–45

    PubMed  CAS  Google Scholar 

  • Park YS, Lee YS, Cho NJ, Kaang BK (2000) Alternative splicing of gar-1, a Caenorhabditis elegans G-protein-linked acetylcholine receptor gene. Biochem Biophys Res Commun 268:354–8

    PubMed  CAS  Google Scholar 

  • Parma J, Duprez L, van Sande J, Cochaux P, Gervy C, Mockel J, Dumont J, Vassart G (1993) Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas. Nature 365:649–51

    PubMed  CAS  Google Scholar 

  • Parma J, Duprez L, Van Sande J, Hermans J, Rocmans P, Van Vliet G, Costagliola S, Rodien P, Dumont JE, Vassart G (1997) Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gsα genes as a cause of toxic thyroid adenomas. J Clin Endocrinol Metab 82:2695–701

    PubMed  CAS  Google Scholar 

  • Pasel K, Schulz A, Timmermann K, Linnemann K, Hoeltzenbein M, Jääskeläinen J, Grüters A, Filler G, Schöneberg T (2000) Functional characterization of the molecular defects causing nephrogenic diabetes insipidus in eight families. J Clin Endocrinol Metab 85:1703–10

    PubMed  CAS  Google Scholar 

  • Perez DM, Hwa J, Gaivin R, Mathur M, Brown F, Graham RM (1996) Constitutive activation of a single effector pathway: evidence for multiple activation states of a G protein-coupled receptor. Mol Pharmacol 49:112–22

    PubMed  CAS  Google Scholar 

  • Perlman JH, Wang W, Nussenzveig DR, Gershengorn MC (1995) A disulfide bond between conserved extracellular cysteines in the thyrotropin-releasing hormone receptor is critical for binding. J Biol Chem 270:24682–5

    PubMed  CAS  Google Scholar 

  • Perlman JH, Colson AO, Wang W, Bence K, Osman R, Gershengorn MC (1997) Interactions between conserved residues in transmenbrane helices 1, 2, and 7 of the thyrotropin-releasing hormone receptor. J Biol Chem 272:11937–42

    PubMed  CAS  Google Scholar 

  • Peroutka SJ, Howell TA (1994) The molecular evolution of G protein-coupled receptors: focus on 5-hydroxytryptamine receptors. Neuropharmacology 33:319–24

    PubMed  CAS  Google Scholar 

  • Pierce KL, Regan JW (1998) Prostanoid receptor heterogeneity through alternative mRNA splicing. Life Sci 62:1479–83

    PubMed  CAS  Google Scholar 

  • Pitteloud N, Boepple PA, DeCruz S, Valkenburgh SB, Crowley WF Jr, Hayes FJ (2001) The fertile eunuch variant of idiopathic hypogonadotropic hypogonadism: spontaneous reversal associated with a homozygous mutation in the gonadotropin-releasing hormone receptor. J Clin Endocrinol Metab 86:2470–5

    PubMed  CAS  Google Scholar 

  • Podesta EJ, Solano AR, Attar R, Sanchez ML, Molina Y, Vedia L (1983) Receptor aggregation induced by antilutropin receptor antibody and biological response in rat testis Leydig cells. Proc Natl Acad Sci USA 80:3986–90

    PubMed  CAS  Google Scholar 

  • Pollak MR, Brown EM, Chou YH, Hebert SC, Marx SJ, Steinmann B, Levi T, Seidman CE, Seidman JG (1993) Mutations in the human Ca2+-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Cell 75:1297–303

    PubMed  CAS  Google Scholar 

  • Porter JE, Hwa J, Perez DM (1996) Activation of the α1b-adrenergic receptor is initiated by disruption of an interhelical salt bridge constraint. J Biol Chem 271:28318–23

    PubMed  CAS  Google Scholar 

  • Prezeau L, Gomeza J, Ahern S, Mary S, Galvez T, Bockaert J, Pin JP (1996) Changes in the carboxyl-terminal domain of metabotropic glutamate receptor 1 by alternative splicing generate receptors with differing agonist-independent activity. Mol Pharmacol 49:422–9

    PubMed  CAS  Google Scholar 

  • Puffenberger EG, Hosoda K, Washington SS, Nakao K, deWit D, Yanagisawa M, Chakravart A (1994) A missense mutation of the endothelin-B, receptor gene in multigenic Hirschsprung's disease. Cell 79:1257–66

    PubMed  CAS  Google Scholar 

  • Rana BK, Shiina T, Insel PA (2001) Genetic variations and polymorphisms of g protein-coupled receptors: functional and therapeutic implications. Ann Rev Pharmacol Toxicol 41:593–624

    CAS  Google Scholar 

  • Rando TA, Disatnik MH, Zhou LZ (2000) Rescue of dystrophin expression in mdx mouse muscle by RNA/DNA oligonucleotides. Proc, Natl Acad Sci USA 97:5363–8

    CAS  Google Scholar 

  • Rands E, Candelore MR, Cheung AH, Hill WS, Strader CD, Dixon RA (1990) Mutational analysis of β-adrenergic receptor glycosylation. J Biol Chem 265:10759–64

    PubMed  CAS  Google Scholar 

  • Rao VR, Cohen GB, Oprian DD (1994) Rhodopsin mutation G90D and a molecular mechanism for congenital night blindness. Nature 367:639–42

    PubMed  CAS  Google Scholar 

  • Rasmussen SG, Jensen AD, Liapakis G, Ghanouni P, Javitch JA, Gether U (1999) Mutation of a highly conserved aspartic acid in the β2 adrenergic receptor: constitutive activation, structural instability, and conformational rearrangement of transmembrane segment 6. Mol Pharmacol 56:175–84

    PubMed  CAS  Google Scholar 

  • Ray K, Clapp P, Goldsmith PK, Spiegel AM (1998) Identification of the sites of N-linked glycosylation on the human calcium receptor and assessment of their role in cell surface expression and signal transduction. J Biol Chem 273:34558–67

    PubMed  CAS  Google Scholar 

  • Redfern CH, Coward P, Degtyarev, MY, Lee EK, Kwa AT, Hennighausen L, Bujard H, Fishman GI, Conklin BR (1999) Conditional expression and signaling of a specifically designed Gi-coupled receptor in transgenic mice. Nat Biotechnol 17:165–9

    PubMed  CAS  Google Scholar 

  • Reig C, Alvarez AI, Tejada I, Molina M, Arostegui E, Martin R, Antich J, Carballo M (1996) New mutation in the 3′-acceptor splice site of intron 4 in the rhodopsin gene associated with autosomal dominant retinitis pigmentosa in a Basque family. Hum Mutat 8:93–4.

    PubMed  CAS  Google Scholar 

  • Ren Q, Kurose H, Lefkowitz RJ, Cotecchia S (1993) Constitutively active mutants of the α2-adrenergic receptor. J Biol Chem 268:16483–7

    PubMed  CAS  Google Scholar 

  • Restagno G, Maghtheh M, Bhattacharya S, Ferrone M, Garnerone S, Samuelly R, Carbonara A (1993) A large deletion at the 3′ end of the rhodopsin gene in an Italian family with a diffuse form of autosomal dominant retinitis pigmentosa. Hum Mol Genet 2:207–8

    PubMed  CAS  Google Scholar 

  • Rhee MH, Nevo I, Levy R, Vogel Z (2000) Role of the highly conserved Asp-Arg-Tyr motif in signal transduction of the CB2 cannabinoid receptor. FEBS Lett 466:300–4

    PubMed  CAS  Google Scholar 

  • Ridge KD, Lee SS, Yao LL (1995) In vivo assembly of rhodopsin from expressed polypeptide fragments. Proc Natl Acad Sci USA 92:3204–8

    PubMed  CAS  Google Scholar 

  • Riek RP, Rigoutsos I, Novotny J, Graham RM (2001) Non-α-helical elements modulate polytopic membrane protein architecture. J Mol Biol 306:349–62

    PubMed  CAS  Google Scholar 

  • Robinson PR, Cohen GB, Zhukovsky EA, Oprian DD (1992) Constitutively active mutants of rhodopsin. Neuron 9:719–25

    PubMed  CAS  Google Scholar 

  • Rocheville M, Lange DC, Kumar U, Patel SC, Patel RC, Patel YC (2000a) Receptors for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activity. Science 288:154–7

    PubMed  CAS  Google Scholar 

  • Rocheville M, Lange DC, Kumar U, Sasi R, Patel RC, Patel YC (2000b) Subtypes of the somatostatin receptor assemble as functional homo-and heterodimers. J Biol Chem 275:7862–9

    PubMed  CAS  Google Scholar 

  • Romano C, Yang WL, O'Malley KL (1996) Metabotropic glutamate receptor 5 is a disulfide-linked dimer. J Biol Chem 271:28612–6

    PubMed  CAS  Google Scholar 

  • Rose PM, Lynch JS, Frazier ST, Fisher SM, Chung W, Battaglino P, Fathi Z, Leibel R, Fernandes P (1997) Molecular genetic analysis of a human neuropeptide Y receptor. The human homolog of the murine “Y5” receptor may be a pseudogene. J Biol Chem 272:3622–7

    PubMed  CAS  Google Scholar 

  • Rosenkilde MM, Kledal TN, Brauner-Osborne H, Schwartz TW (1999) Agonists and inverse agonists for the herpesvirus 8-encoded constitutively active seven-transmembrane oncogene product, ORF-74. J Biol Chem 274:956–61

    PubMed  CAS  Google Scholar 

  • Rosenthal W, Seibold A, Antaramian A, Lonergan M, Arthus MF, Hendy GN, Birnbaumer M, Bichet DG (1992) Molecular identification of the gene responsible for congenital nephrogenic diabetes insipidus. Nature 359:233–5

    PubMed  CAS  Google Scholar 

  • Rotondo A, Nielsen DA, Nakhai B, Hulihan-Giblin B, Bolos A, Goldman D (1997) Agonist-promoted down-regulation and functional desensitization in two naturally occurring variants of the human serotonin1A receptor. Neuropsychopharmacology 17:18–26

    PubMed  CAS  Google Scholar 

  • Royant A, Nollert P, Edman K, Neutze R, Landau EM, Pebay-Peyroula E, Navarro J (2001) X-ray structure of sensory rhodopsin II at 2.1-Å resolution. Proc Natl Acad Sci USA 98:10131–6

    PubMed  CAS  Google Scholar 

  • Rozell TG, Davis DP, Chai Y, Segaloff DL (1998) Association of gonadotropin receptor precursors with the protein folding chaperone calnexin. Endocrinology 139:1588–93

    PubMed  CAS  Google Scholar 

  • Rubinstein M, Phillips TJ, Bunzow JR, Falzone TL, Dziewczapolski G, Zhang G, Fang Y, Larson JL, McDougall JA, Chester JA, Saez C, Pugsley TA, Gershanik O, Low MJ, Grandy DK (1997) Mice lacking dopamine D4 receptors are supersensitive to ethanol, cocaine, and methamphetamine. Cell 90:991–1001

    PubMed  CAS  Google Scholar 

  • Russo D, Arturi F, Schlumberger M, Caillou B, Monier R, Filetti S, Suarez HG (1995) Activating mutations of the TSH receptor in differentiated thyroid carcinomas. Oncogene 11:1907–11

    PubMed  CAS  Google Scholar 

  • Russo D, Arturi F, Suarez HG, Schlumberger M, Du Villard JA, Crocetti U, Filetti S (1996) Thyrotropin receptor gene alterations in thyroid hyperfunctioning adenomas. J Clin Endocrinol Metab 81:1548–51

    PubMed  CAS  Google Scholar 

  • Sadeghi H, Birnbaumer M (1999) O-Glycosylation of the V2 vasopressin receptor. Glycobiology 9:731–7

    PubMed  CAS  Google Scholar 

  • Sadeghi HM, Innamorati G, Birnbaumer M (1997a) An X-linked NDI mutation reveals a requirement for cell surface V2R expression. Mol Endocrinol 11:706–13

    PubMed  CAS  Google Scholar 

  • Sadeghi H, Robertson GL, Bichet DG, Innamorati G, Birnbaumer M (1997b) Biochemical basis of partial nephrogenic diabetes insipidus phenotypes. Mol Endocrinol 11:1806–13

    PubMed  CAS  Google Scholar 

  • Samama P, Bond RA, Rockman HA, Milano CA, Lefkowitz RJ (1997) Ligand-induced overexpression of a constitutively active β2-adrenergic receptor: pharmacological creation of a phenotype in transgenic mice. Proc Natl Acad Sci USA 94:137–41

    PubMed  CAS  Google Scholar 

  • Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C, Farber CM, Saragosti S, Lapoumeroulie C, Cognaux J, Forceille C, Muyldermans G, Verhofstede C, Burtonboy G, Georges M, Imai T, Rana S, Yi Y, Smyth RJ, Collman RG, Doms RW, Vassart G, Parmentier M (1996) Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 382:722–5

    PubMed  CAS  Google Scholar 

  • Sato S, Ward C, Krouse ME, Wine JJ, Kopito RR (1996) Glycerol reverses the misfolding phenotype of the most common cystic fibrosis mutation. J Biol Chem 271:635–8

    PubMed  CAS  Google Scholar 

  • Savarese TM, Wang CD, Fraser CM (1992) Site-directed mutagenesis of the rat m1 muscarinic acetylcholine receptor. Role of conserved cysteines in receptor function. J Biol Chem 267:11439–48

    PubMed  CAS  Google Scholar 

  • Scheer A, Fanelli F, Costa T, De Benedetti PG, Cotecchia S (1996) Constitutively active mutants of the α1B-adrenergic receptor: role of highly conserved polar amino acids in receptor activation. EMBO J 15:3566–78

    PubMed  CAS  Google Scholar 

  • Scheer A, Fanelli F, Costa T, De Benedetti PG, Cotecchia S (1997) The activation process of the α1B-adrenergic receptor: potential role of protonation and hydrophobicity of a highly conserved aspartate. Proc Natl Acad Sci USA 94:808–13

    PubMed  CAS  Google Scholar 

  • Schipani E, Kruse K, Juppner H (1995) A constitutively active mutant PTH-PTHrP receptor in Jansen-type metaphyseal chondrodysplasia. Science 268:98–100

    PubMed  CAS  Google Scholar 

  • Schipani E, Lanske B, Hunzelman J, Luz A, Kovacs CS, Lee K, Pirro A, Kronenberg HM, Juppner H (1997) Targeted expression of constitutively active receptors for parathyroid hormone and parathyroid hormone-related peptide delays endochondral bone formation and rescues mice that lack parathyroid hormone-related peptide. Proc Natl Acad Sci USA 94:13689–94

    PubMed  CAS  Google Scholar 

  • Schöneberg T, Liu J, Wess J (1995) Plasma membrane localization and functional rescue of truncated forms of a G protein-coupled receptor. J Biol Chem 270:18000–6.

    PubMed  Google Scholar 

  • Schöneberg T, Yun J, Wenkert D, Wess J (1996) Functional rescue of mutant V2 vasopressin receptors causing nephrogenic diabetes insipidus by a co-expressed receptor polypeptide. EMBO J 15:1283–91

    PubMed  Google Scholar 

  • Schöneberg T, Sandig V, Wess J, Gudermann T, Schultz G (1997) Reconstitution of mutant V2 vasopressin receptors by adenovirus-mediated gene transfer. Molecular basis and clinical implication. J Clin Invest 100:1547–56

    PubMed  Google Scholar 

  • Schöneberg T, Schulz A, Biebermann H, Grüters A, Grimm T, Hübschmann K, Filler G, Gudermann T, Schultz G (1998) V2 vasopressin receptor dysfunction in nephrogenic diabetes insipidus caused by different molecular mechanisms. Hum Mutat 12:196–205

    PubMed  Google Scholar 

  • Schöneberg T, Pasel K, von Baehr V, Schulz A, Volk HD, Gudermann T, Filler G (1999) Compound deletion of the rhoGAP C1 and V2 vasopressin receptor genes in a patient with nephrogenic diabetes insipidus. Hum Mutat 14:163–74

    PubMed  Google Scholar 

  • Schülein R, Hermosilla R, Oksche A, Dehe M, Wiesner B, Krause G, Rosenthal W (1998) A dileucine sequence and an upstream glutamate residue in the intracellular carboxyl terminus of the vasopressin V2 receptor are essential for cell surface transport in COS.M6 cells. Mol, Pharmacol 54:525–35

    Google Scholar 

  • Schülein R, Zühlke K, Krause G, Rosenthal W (2000) Functional rescue of three vasopressin V2 receptor mutants causing nephrogenic diabetes insipidus by a second site suppressor mutation. J Biol Chem 276:8384–92

    PubMed  Google Scholar 

  • Schulz A, Schöneberg T, Paschke R, Schultz G, Gudermann T (1999) Role of the third intracellular loop for the activation of gonadotropin receptors. Mol Endocrinol 13:181–90

    PubMed  CAS  Google Scholar 

  • Schulz A, Bruns C, Henklein P, Krause G, Schubert M, Gudermann T, Wray V, Schultz G, Schöneberg T (2000a) Requirement of specific intrahelical interactions for stabilizing the inactive conformation of glycoprotein hormone receptors. J Biol Chem 275:37860–9

    PubMed  CAS  Google Scholar 

  • Schulz A, Grosse R, Schutz G, Gudermann T, Schöneberg T (2000b) Structural implication for receptor oligomerization from functional reconstitution studies of mutant V2 vasopressin receptors. J Biol Chem 275:2381–9

    PubMed  CAS  Google Scholar 

  • Schulz A, Schöneberg T (2000c) Analysis of molecular mechanisms causing V2 vasopressin receptor dysfunction in 8 NDI families. NDI Conference—La Jolla, March 10–12

    Google Scholar 

  • Schwarzler A, Kreienkamp HJ, Richter D (2000) Interaction of the somatostatin receptor subtype 1 with the human homolog of the Shk1 kinase-binding protein from yeast. J Biol Chem 275:9557–62

    PubMed  CAS  Google Scholar 

  • Seeman P, Nam D, Ulpian C, Liu IS, Tallerico T (2000) New dopamine receptor, D2(Longer), with unique TG splice site, in human brain. Brain Res Mol Brain Res 76:132–41

    PubMed  CAS  Google Scholar 

  • Seibold A, Dagarag M, Birnbaumer M (1998) Mutations of the DRY motif that preserve β2-adrenoceptor coupling. Receptors Channels 5:375–85

    PubMed  CAS  Google Scholar 

  • Sheikh SP, Zvyaga TA, Lichtarge O, Sakmar TP, Bourne HR (1996) Rhodopsin activation blocked by metal-ion-binding sites linking transmembrane helices C and F. Nature 383:347–50

    PubMed  CAS  Google Scholar 

  • Shenker A, Laue L, Kosugi S, Merendino JJ Jr, Minegishi T, Cutler GB Jr (1993) A constituvely activating mutation of the luteinizing hormone receptor in familial male precocious puberty. Nature 365:652–4

    PubMed  CAS  Google Scholar 

  • Shibata K, Hirasawa A, Moriyama N, Kawabe K, Ogawa S, Tsujimoto G (1996) a1a-adrenoceptor polymorphism: pharmacological characterization and association with benign prostatic hypertrophy. Br J Pharmacol 118:1403–8

    PubMed  CAS  Google Scholar 

  • Shima Y, Tsukada T, Nakanishi K, Ohta H (1998) Association of the Trp64Arg mutation of the β3-adrenergic receptor with fatty liver and mild glucose intolerance in Japanese subjects. Clin Chim Acta 274:167–76

    PubMed  CAS  Google Scholar 

  • Sims KB, Ozelius L, Corey T, Rinehart WB, Liberfarb R, Haines J, Chen WJ, Norio R, Sankila E, de la Chapelle A (1989) Norrie disease gene is distinct from the monoamine oxidase genes. Am J Hum Genet 45:424–34

    PubMed  CAS  Google Scholar 

  • Sina M, Hinney A, Ziegler A, Neupert T, Mayer H, Siegfried W, Blum WF, Remschmidt H, Hebebrand J (1999) Phenotypes in three pedigrees with autoso-mal dominant obesity caused by haploinsufficiency mutations in the melanocortin-4 receptor gene. Am J Hum Genet 65:1501–7

    PubMed  CAS  Google Scholar 

  • Singh N, Zanusso G, Chen SG, Fujioka H, Richardson S, Gambetti P, Petersen RB (1997) Prion protein aggregation reverted by low temperature in transfected cells carrying a prion protein gene mutation. J Biol Chem 272:28461–70

    PubMed  CAS  Google Scholar 

  • Small K, Iber J, Warren ST (1997) Emerin deletion reveals a common X-chromosome inversion mediated by inverted repeats. Nat Genet 16:96–9

    PubMed  CAS  Google Scholar 

  • Small KM, Forbes SL, Bridges K, Liggett SB (2000) An Asn to Lys polymorphism in the third intracellular loop of the human β2-adrenergic receptor imparts enhanced agonist-promoted Gi coupling. J Biol Chem 275:38518–23

    PubMed  CAS  Google Scholar 

  • Small KM, Brown KM, Forbes SL, Liggett SB (2001) Modification of the β2-adrenergic receptor to, engineer a receptor-effector complex for gene therapy. J Biol Chem 276:31596–601

    PubMed  CAS  Google Scholar 

  • Smit MJ, Leurs R, Alewijnse AE, Blauw J, Van Nieuw Amerongen GP, Van De Vrede Y, Roovers E, Timmerman H (1996) Inverse agonism of histamine H2 antagonist accounts for upregulation of spontaneously active histamine H2 receptors. Proc Natl Acad Sci USA 93:6802–7

    PubMed  CAS  Google Scholar 

  • Smith MW, Dean M, Carrington M, Winkler C, Huttley GA, Lomb DA, Goedert JJ, O'Brien TR, Jacobson LP, Kaslow R, Buchbinder S, Vittinghoff E, Vlahov D, Hoots K, Hilgartner MW, O'Brien SJ (1997) Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study. Science 277:959–65

    PubMed  CAS  Google Scholar 

  • Sobell, JL, Lind TJ, Sigurdson DC, Zald DH, Snitz BE, Grove WM, Heston LL, Sommer SS (1995) The D5 dopamine receptor gene in schizophrenia: identification of a nonsense change and multiple missense changes but lack of association with disease. Hum. Mol Genet 4:507–14

    PubMed  CAS  Google Scholar 

  • Stacey M, Lin HH, Gordon S, McKnight AJ (2000) LNB-TM7, a group of seventransmembrane proteins related to family-B G-protein-coupled receptors. Trends Biochem. Sci 25:284–9

    PubMed  CAS  Google Scholar 

  • Stein SA, Oates EL, Hall CR, Grumbles RM, Fernandez LM, Taylor NA, Puett D, Jin S (1994) Identification of a point mutation in the thyrotropin receptor of the hyt/hyt hypothyroid mouse. Mol Endocrinol 8:129–38

    PubMed  CAS  Google Scholar 

  • Stühmer W, Conti F, Suzuki H, Wang XD, Noda M, Yahagi N, Kubo H, Numa S (1989) Structural parts involved in activation and inactivation of the sodium channel. Nature 339:597–603

    PubMed  Google Scholar 

  • Sullivan LJ, Makris GS, Dickinson P, Mulhall LE, Forrest S, Cotton RG, Loughnan MS (1993) A new codon 15 rhodopsin gene mutation in autosomal dominant retinitis pigmentosa is associated with sectorial disease. Arch Ophthalmol 111:1512–7

    PubMed  CAS  Google Scholar 

  • Sung CH, Schneider BG, Agarwal N, Papermaster DS, Nathans J (1991) Functional heterogeneity of mutant rhodopsins responsible for autosomal dominant retinitis pigmentosa. Proc Natl Acad Sci USA: 88:8840–4

    PubMed  CAS  Google Scholar 

  • Sunthornthepvarakui T, Gottschalk ME, Hayashi Y, Refetoff S (1995) Brief report: resistance to thyrotropin caused by mutations in the thyrotropin-receptor gene. N Engl J Med 332:155–60

    PubMed  CAS  Google Scholar 

  • Surprenant A, Horstman DA, Akbarali H, Limbird LE (1992) A point mutation of the β2-adrenoceptor that blocks coupling to potassium but not calcium currents. Science 257:977–80

    PubMed  CAS  Google Scholar 

  • Taboulet J, Frenkian M, Frendo JL, Feingold N, Jullienne A, de Vernejoul MC (1998) Calcitonin receptor polymorphism is associated with a decreased fracture risk in post-menopausal women. Hum Mol Genet 7:2129–33

    PubMed  CAS  Google Scholar 

  • Tajima T, Nakae J, Takekoshi Y, Takekoshi Y, Yuri K, Nagashima T, Fujieda K (1996) Three novel AVPR2 mutations in three Japanese families with X-linked nephrogenic diabetes insipidus. Pediatr Res 39:522–6

    PubMed  CAS  Google Scholar 

  • Takagi Y, Ninomiya H, Sakamoto A, Miwa S, Masaki T (1995) Structural basis of G protein specificity of human endothelin receptors. A study with endothelinA/B chimeras. J Biol Chem 270:10072–8

    PubMed  CAS  Google Scholar 

  • Tamarappoo BK, Verkman AS (1998) Defective aquaporin-2 trafficking in nephrogenic diabetes insipidus and correction by chemical chaperones. J Clin Invest 101:2257–67

    PubMed  CAS  Google Scholar 

  • Tang WJ, Stanzel M, Gilman AG (1995) Truncation and alanine-scanning mutants of type I adenylyl cyclase. Biochemistry 34:14563–72

    PubMed  CAS  Google Scholar 

  • Tang Y, Hu LA, Miller WE, Ringstad N, Hall RA, Pitcher JA, DeCamilli P, Lefkowitz RJ (1999) Identification of the endophilins (SH3p4/p8/p13) as novel binding partners for the β1-adrenergic receptor. Proc Natl Acad Sci USA 96:12559–64

    PubMed  CAS  Google Scholar 

  • Tarasova NI, Rice WG, Michejda CJ (1999) Inhibition of G-protein-coupled receptor function by disruption of transmembrane domain interactions. J Biol Chem 274:34911–5

    PubMed  CAS  Google Scholar 

  • Teller DC, Okada T, Behnke CA, Palczewski K, Stenkamp RE (2001) Advances in determination of a high-resolution three-dimensional structure of rhodopsin, a model of g-protein-coupled receptors (gpcrs). Biochemistry 40:7761–72

    PubMed  CAS  Google Scholar 

  • Tharapel AT, Anderson KP, Simpson JL, Martens PR, Wilroy Jr RS, Llerena Jr JC and Schwartz CE (1993) Deletion Xq26.1→q28 in a proband and her mother: molecular characterization and phenotypic-karyotypic deductions. Am J Hum Genet 52:463–71

    PubMed  CAS  Google Scholar 

  • The genome international sequencing consortium (2001) Initial sequencing and analysis of the human genome. Nature 409:860–921

    Google Scholar 

  • Thompson JB, Wade SM, Harrison JK, Salafranca MN, Neubig RR (1998) Cotransfection of second and third intracellular loop fragments inhibit angiotensin AT1a receptor activation of phospholipase C in HEK-293 cells. J Pharmacol Exp Ther 285:216–22

    PubMed  CAS  Google Scholar 

  • Tiberi M, Caron MG (1994) High agonist-independent activity is a distinguishing feature of the dopamine D1B receptor subtype. J Biol Chem 269:27925–31

    PubMed  CAS  Google Scholar 

  • Tonacchera M, Chiovato L, Pinchera A, Agretti P, Fiore E, Cetani F, Rocchi R, Viacava P, Miccoli P, Vitti P (1998) Hyperfunctioning thyroid nodules in toxic multinodular goiter share activating thyrotropin receptor mutations with solitary toxic adenoma. J Clin Endocrinol Metab 83:492–8

    PubMed  CAS  Google Scholar 

  • Tonacchera M, Van Sande J, Cetani F, Swillens S, Schvartz C, Winiszewski P, Portmann L, Dumont JE, Vassart G, Parma J (1996) Functional characteristics of three new germline mutations of the thyrotropin receptor gene causing autosomal dominant toxic thyroid hyperplasia. J Clin Endocrinol Metab 81:547–54

    PubMed  CAS  Google Scholar 

  • Tribioli C, Droetto S, Bione S, Cesareni G, Torrisi MR, Lotti LV, Lanfrancone L, Toniolo D, Pelicci P (1996) An X chromosome-linked gene encoding a protein with characteristics of a rhoGAP predominantly expressed in hematopoietic cells. Proc Natl Acad Sci USA 93:695–9

    PubMed  CAS  Google Scholar 

  • Tu JC, Xiao B, Yuan JP, Lanahan AA, Leoffert K, Li M, Linden DJ, Worley PF (1998) Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors. Neuron 21:717–26

    PubMed  CAS  Google Scholar 

  • Tulman ER, Afonso CL, Lu Z, Zsak L, Kutish GF, Rock DL (2001) Genome of lumpy skin disease virus. J Virol 75:7122–30

    PubMed  CAS  Google Scholar 

  • Turki J, Pak J, Green SA, Martin RJ, Liggett SB (1995) Genetic polymorphisms of the β2-adrenergic receptor in nocturnal and nonnocturnal asthma. Evidence that Gly16 correlates with the nocturnal phenotype. J Clin Invest 95:1635–41

    PubMed  CAS  Google Scholar 

  • Ullmer C, Schmuck K, Figge A, Lubbert H (1998) Cloning and characterization of MUPP1, a novel PDZ domain protein. FEBS Lett 424:63–8

    PubMed  CAS  Google Scholar 

  • Ulloa-Aguirre A, Stanislaus D, Arora V, Vaananen J, Brothers S, Janovick JA, Conn PM (1998) The third intracellular loop of the rat gonadotropin-releasing hormone receptor couples the receptor to G5-and Gq/11-mediated signal transduction pathways: evidence from loop fragment transfection in GGH3 cells. Endocrinology 139:2472–8

    PubMed  CAS  Google Scholar 

  • Ulrich CD 2nd, Holtmann M and Miller LJ (1998) Secretin and vasoactive intestinal peptide receptors: members of a unique family of G protein-coupled receptors. Gastroenterology 114:382–97

    PubMed  CAS  Google Scholar 

  • Unger VM, Hargrave PA, Baldwin JM, Schertler GF (1997) Arrangement of rhodopsin transmembrane a-helices. Nature 389:203–6

    PubMed  CAS  Google Scholar 

  • Unson CG, Cypess AM, Kim HN, Goldsmith PK, Carruthers CJ, Merrifield RB, Sakmar TP (1995) Characterization of deletion and truncation mutants of the rat glucagon receptor. Seven transmembrane segments are necessary for receptor transport to the plasma membrane and glucagon binding. J Biol Chem 270:27720–7

    PubMed  CAS  Google Scholar 

  • Vaisse C, Clement K, Guy-Grand B, Froguel P (1998) A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nat Genet 20:113–4

    PubMed  CAS  Google Scholar 

  • Valverde P, Healy E, Jackson I, Rees JL, Thody AJ (1995) Variants of the melanocytestimulating hormone receptor gene are associated with red hair and fair skin in humans. Nat Genet 11:328–30

    PubMed  CAS  Google Scholar 

  • van Geel PP, Pinto YM, Voors AA, Buikema H, Oosterga M, Crijns HJ, van Gilst WH (2000) Angiotensin II type 1 receptor A1166C gene polymorphism is associated with an increased response to angiotensin II in human arteries. Hypertension 35:717–21

    PubMed  Google Scholar 

  • van Lieburg AF, Verdijk MA, Schoute F, Ligtenberg MJ, van Oost BA, Waldhauser F, Dobner M, Monnens LA, Knoers NV (1995) Clinical phenotype of nephrogenic diabetes insipidus in females heterozygous for a vasopressin type 2 receptor mutation. Hum Genet 96:70–8

    PubMed  Google Scholar 

  • Varrault A, Le Nguyen D, McClue S, Harris B, Jouin P, Bockaert J (1994) 5-Hydroxytryptamine 1A receptor synthetic peptides. Mechanisms of adenylyl cyclase inhibition. J Biol Chem 269:16720–5

    PubMed  CAS  Google Scholar 

  • Venkatesh B, Ning Y, Brenner S (1999) Late changes in spliceosomal introns define clades in vertebrate evolution. Proc Natl Acad Sci USA 96:10267–71

    PubMed  CAS  Google Scholar 

  • Venter JC et al. (2001) The sequence of the human genome. Science 29:1304–51

    Google Scholar 

  • Vezza R, Habib A, FitzGerald GA (1999) Differential signaling by the thromboxane receptor isoforms via the novel GTP-binding protein, Gh. J Biol Chem 274:12774–9

    PubMed  CAS  Google Scholar 

  • Vila-Coro AJ, Rodriguez-Frade JM, Martin De Ana A, Moreno-Ortiz MC, Martinez-A C, Mellado M (1999) The chemokine SDF-1α triggers CXCR4 receptor dimerization and activates the JAK/STAT pathway. FASEB J 13:1699–710

    PubMed  CAS  Google Scholar 

  • Villar AJ, Pedersen RA (1994) Parental imprinting of the Mas protooncogene in mouse. Nat Genet 8:373–9

    PubMed  CAS  Google Scholar 

  • Wajnrajch MP, Gertner JM, Harbison MD, Chua SC Jr, Leibel RL (1996) Nonsense mutation in the human growth hormone-releasing hormone receptor causes growth failure analogous to the little (lit) mouse. Nat Genet 12:88–90

    PubMed  CAS  Google Scholar 

  • Walz T, Hirai T, Murata K, Heymann JB, Mitsuoka K, Fujiyoshi Y, Smith BL, Agre P, Engel A (1997) The three-dimensional structure of aquaporin-1. Nature 387: 624–7

    PubMed  CAS  Google Scholar 

  • Wang Z, Hipkin RW, Ascoli M (1996) Progressive cytoplasmic tail truncations of the lutropin-choriogonadotropin receptor prevent agonist-or phorbol ester-induced phosphorylation, impair agonist-or phorbol ester-induced desensitization, and enhance agonist-induced receptor down-regulation. Mol Endocrinol 10:748–59

    PubMed  CAS  Google Scholar 

  • Ward DT, Brown EM, Harris HW (1998) Disulfide bonds in the extracellular calcium-polyvalent cation-sensing receptor correlate with dimer formation and its response to divalent cations in vitro. J Biol Chem 273:14476–83

    PubMed  CAS  Google Scholar 

  • Weinstein LS, Yu S (1999) The role of genomic imprinting of Ga in the pathogenesis of Albright Hereditary Osteodystrophy. Trends Endocrinol Metab 10:81–5

    PubMed  CAS  Google Scholar 

  • Weitz CJ, Miyake Y, Shinzato K, Montag E, Zrenner E, Went LN, Nathans J (1992) Human tritanopia associated with two amino acid substitutions in the bluesensitive opsin. Am J Hum, Genet 50:498–507

    CAS  Google Scholar 

  • Wenkert D, Schöneberg T, Merendino JJ Jr, Rodriguez Pena MS, Vinitsky R, Goldsmith PK, Wess J, Spiegel AM (1996) Functional characterization of five V2 vasopressin receptor gene mutations. Mol Cell Endocrinol 124:43–50

    PubMed  CAS  Google Scholar 

  • Wess J (1998) Molecular basis of receptor/G-protein-coupling selectivity. Pharmacol Ther 80:231–64

    PubMed  CAS  Google Scholar 

  • West AP Jr, Llamas LL, Snow PM, Benzer S, Bjorkman PJ (2001) Crystal structure of the ectodomain of Methuselah, a Drosophila G protein-coupled receptor associated with extended lifespan. Proc Natl Acad Sci USA 98:3744–9

    PubMed  CAS  Google Scholar 

  • Westphal RS, Backstrom JR, Sanders-Bush E (1995) Increased basal phosphorylation of the constitutively active serotonin 2C receptor accompanies agonist-mediated desensitization. Mol Pharmacol 48:200–5

    PubMed  CAS  Google Scholar 

  • White DC, Hata JA, Shah AS, Glower DD, Lefkowitz RJ, Koch WJ (2000) Preservation of myocardial ß-adrenergic receptor signaling delays the development of heart failure after myocardial infarction. Proc. Natl Acad Sci USA 97:5428–33

    PubMed  CAS  Google Scholar 

  • White JH, Wise A, Main MJ, Green A, Fraser NJ, Disney GH, Barnes AA, Emson P, Foord SM, Marshall FH (1998) Heterodimerization is required for the formation of a functional GABAB receptor. Nature 396:679–82

    PubMed  CAS  Google Scholar 

  • Wildin RS, Antush MJ, Bennett RL, Schoof JM, Scott CR (1994) Heterogeneous AVPR2 gene mutations in congenital nephrogenic diabetes insipidus. Am J Human Genetics 55:266–77

    CAS  Google Scholar 

  • Wildin RS, Cogdell DE, Valadez V (1998) AVPR2 variants and V2 vasopressin receptor function in nephrogenic diabetes insipidus. Kidney Int 54:1909–22

    PubMed  CAS  Google Scholar 

  • Williams J, Spurlock G, McGuffin P, Mallet J, Nothen MM, Gill M, Aschauer H, Nylander PO, Macciardi F, Owen MJ (1996) Association between schizophrenia and T102C polymorphism of the 5-hydroxytryptamine type 2a-receptor gene. European Multicentre Association Study of Schizophrenia (EMASS) Group. Lancet 347:1294–6

    PubMed  CAS  Google Scholar 

  • Wonerow P, Schöneberg T, Schultz G, Gudermann T, Paschke R (1998) Deletions in the third intracellular loop of the thyrotropin receptor. A new mechanism for constitutive activation. J Biol Chem 273:7900–5

    PubMed  CAS  Google Scholar 

  • Wu V, Yang M, McRoberts JA, Ren J, Seensalu R, Zeng N, Dagrag M, Birnbaumer M, Walsh JH (1997) First intracellular loop of the human cholecystokinin-A receptor is essential for cyclic AMP signaling in transfected HEK-293 cells. J Biol Chem 272:9037–42

    PubMed  CAS  Google Scholar 

  • Xiao B, Tu JC, Petralia RS, Yuan JP, Doan A, Breder CD, Ruggiero A, Lanahan AA, Wenthold RJ, Worley PF (1998) Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of homer-related, synaptic proteins. Neuron 21:707–16

    PubMed  CAS  Google Scholar 

  • Xie J, Murone M, Luoh SM, Ryan A, Gu Q, Zhang C, Bonifas JM, Lam CW, Hynes M, Goddard A, Rosenthal A, Epstein EH Jr, de Sauvage FJ (1998) Activating Smoothened mutations in sporadic basal-cell carcinoma. Nature 391:90–2

    PubMed  CAS  Google Scholar 

  • Xie Z, Lee SP, O'Dowd BF, George SR (1999) Serotonin 5-HT1B and 5-HT1D receptors form homodimers when expressed alone and heterodimers when co-expressed. FEBS Lett 456:63–7

    PubMed  CAS  Google Scholar 

  • Yang T, Snider BB, Oprian DD (1997) Synthesis and characterization of a novel retinylamine analog inhibitor of constitutively active rhodopsin mutants found in patients with autosomal dominant retinitis pigmentosa. Proc Natl Acad Sci USA 94:13559–64

    PubMed  CAS  Google Scholar 

  • Yeagle PL, Alderfer JL, Albert AD (1997) Three-dimensional structure of the cyto-plasmic face of the G protein receptor rhodopsin. Biochemistry 36:9649–54

    PubMed  CAS  Google Scholar 

  • Yeo GS, Farooqi IS, Aminian S, Halsall DJ, Stanhope RG, O'Rahilly S (1998) A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat Genet 20:111–2

    PubMed  CAS  Google Scholar 

  • Yuan C, Byeon IJ, Li Y, Tsai MD (1999) Structural analysis of phospholipase A2 from functional perspective. 1. Functionally relevant solution structure and roles of the hydrogen-bonding network. Biochemistry 38:2909–18

    PubMed  CAS  Google Scholar 

  • Yun J, Schöneberg T, Liu J, Schulz A, Ecelbarger CA, Promeneur D, Nielsen S, Sheng H, Grinberg A, Deng C, Wess J (2000) Generation of a mouse model for X-linked nephrogenic diabetes insipidus. J Clin, Invest 106:1361–71

    CAS  Google Scholar 

  • Zawarynski P, Tallerico T, Seeman P, Lee SP, O'Dowd BF, George SR (1998) Dopamine D2 receptor dimers in human and rat brain. FEBS Lett 441:383–6

    PubMed  CAS  Google Scholar 

  • Zeitlin PL (2000) Pharmacologic restoration of delta F508 CFTR-mediated chloride current. Kidney Int 57:832–7

    PubMed  CAS  Google Scholar 

  • Zen KH, McKenna E, Bibi E, Hardy D, Kaback HR (1994) Expression of lactose permease in contiguous fragments as a probe for membrane-spanning domains. Biochemistry 33:8198–206

    PubMed  CAS  Google Scholar 

  • Zeng FY, Soldner A, Schöneberg T, Wess J (1999) Putative disulfide bond in the m3 muscarinic acetylcholine receptor is essential for proper receptor trafficking but not for receptor stability and G protein coupling. J Neurochem 72:2404–14

    PubMed  CAS  Google Scholar 

  • Zeng FY, Wess J (1999) Identification and molecular characterization of m3 muscarinic receptor dimers. J Biol Chem 274:19487–97

    PubMed  CAS  Google Scholar 

  • Zhang P, Jobert AS, Couvineau A, Silve C (1998) A homozygous inactivating mutation in the parathyroid hormone/parathyroid hormone-related peptide receptor causing Blomstrand chondrodysplasia. J Clin Endocrinol Metab 83:3365–8

    PubMed  CAS  Google Scholar 

  • Zhang R, Cai H, Fatima N, Buczko E, Dufau ML (1995) Functional glycosylation sites of the rat luteinizing hormone receptor required for ligand binding. J Biol Chem 270:21722–8

    PubMed  CAS  Google Scholar 

  • Zhang Z, Sun S, Quinn SJ, Brown EM, Bai M (2000) The extracellular calciumsensing receptor dimerizes through multiple types of intermolecular interactions. J Biol Chem 276:5316–22

    PubMed  Google Scholar 

  • Zhou AT, Assil I, Abou-Samra AB (2000) Role of asparagine-linked oligosaccharides in the function of the rat PTH/PTHrP receptor. Biochemistry 39:6514–20

    PubMed  CAS  Google Scholar 

  • Zhu SZ, Wang SZ, Hu J, el-Fakahany EE (1994) An arginine residue conserved in most G protein-coupled receptors is essential for the function of the m1 muscarinic receptor. Mol Pharmacol 45:517–23

    PubMed  CAS  Google Scholar 

  • Zhu X, Gudermann T, Birnbaumer M, Birnbaumer L (1993) A luteinizing hormone receptor with a severely truncated cytoplasmic tail (LHR-ct628) desensitizes to the same degree as the full-length receptor. J Biol Chem 268:1723–8

    PubMed  CAS  Google Scholar 

  • Zhu X, Wess J (1998) Truncated V2 vasopressin receptors as negative regulators of wild-type V2 receptor function. Biochemistry 37:15773–84

    PubMed  CAS  Google Scholar 

  • Zielenski J (2000) Genotype and phenotype in cystic fibrosis. Respiration 67:117–33

    PubMed  CAS  Google Scholar 

  • Zitzer H, Honck HH, Bachner D, Richter D, Kreienkamp HJ (1999) Somatostatin receptor interacting protein defines a novel family of multidomain proteins present in human and rodent brain. J Biol Chem 274:32997–3001

    PubMed  CAS  Google Scholar 

  • Zitzmann M, Nieschlag E (2000) Hormone substitution in male hypogonadism. Mol Cell Endocrinol 161:73–88

    PubMed  CAS  Google Scholar 

  • Zuscik MJ, Porter JE, Gaivin R, Perez DM (1998) Identification of a conserved switch residue responsible for selective constitutive activation of the β2-adrenergic receptor. J Biol Chem 273:3401–7

    PubMed  CAS  Google Scholar 

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Schöneberg, T., Schulz, A., Gudermann, T. (2002). The structural basis of g-protein-coupled receptor function and dysfunction in human diseases. In: Reviews of Physiology, Biochemistry and Pharmacology. Reviews of Physiology, Biochemistry and Pharmacology, vol 144. Springer, Berlin, Heidelberg. https://doi.org/10.1007/BFb0116587

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