Probing receptor structure/function with chimeric G-protein-coupled receptors

Molecular Pharmacology

Volumn 65, Issue 6, 2004, Pages 1323-1332

  Yin, Dezhong ^a   Gavi, Shai ^a   Wang, Hsien Yu ^a,b   Malbon, Craig C ^a,c  

^a STONY BROOK UNIVERSITY MEDICAL CENTER   (United States)

^b STONY BROOK UNIVERSITY   (United States)

^c STONY BROOK UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

G PROTEIN COUPLED RECEPTOR; GONADORELIN; HETEROTRIMERIC GUANINE NUCLEOTIDE BINDING PROTEIN; LIGAND; METABOTROPIC RECEPTOR; MUSCARINIC RECEPTOR; THYROTROPIN;

CHIMERA; PRIORITY JOURNAL; PROTEIN STRUCTURE; RECEPTOR BINDING; RECEPTOR INTRINSIC ACTIVITY; RECEPTOR UPREGULATION; SHORT SURVEY; STRUCTURE ANALYSIS;

ANIMALS; HUMANS; MEMBRANE PROTEINS; PROTEIN CONFORMATION; RECEPTORS, G-PROTEIN-COUPLED; RECOMBINANT FUSION PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 2442716363     PISSN: 0026895X     EISSN: None     Source Type: Journal    
DOI: 10.1124/mol.65.6.1323     Document Type: Short Survey

References (133)

1. Ahumada A, Slusarski DC, Liu X, Moon RT, Malbon CC, and Wang HY (2002) Signaling of rat frizzled-2 through phosphodiesterase and cyclic GMP. Science (Wash DC) 298:2006-2010.
2. Ahumada A and Wang HY. Chimeric G-protein receptors: critical new tools in drug discovery. Pharmaceutical News 9:337-345.
3. Akamizu T, Inoue D, Kosugi S, Ban T, Kohn LD, Imura H, and Mori T (1993) Chimeric studies of the extracellular domain of the rat thyrotropin (TSH) receptor: amino acids (268-304) in the TSH receptor are involved in ligand high affinity binding, but not in TSH receptor-specific signal transduction. Endocr J 40:363-372.
4. Alberts GL, Chio CL, Im WB, and Slightom JL (2003) A unique phenotype of 5-HT2C, agonist-induced GTPgamma35S binding, transferable to 5-HT2A and 5-HT2B, upon swapping intracellular regions. Br J Pharmacol 138:427-434.
5. Alberts GL, Pregenzer JF, and Im WB (1998) Identification of transmembrane regions critical for ligand binding to the human D3 dopamine receptor using various D3/D1 transmembrane chimeras. Mol Pharmacol 54:379-388.
6. Anborgh PH, Seachrist JL, Dale LB, and Ferguson SS (2000) Receptor/beta-arrestin complex formation and the differential trafficking and resensitization of beta2-adrenergic and angiotensin II type 1A receptors. Mol Endocrinol 14:2040-2053.
7. Bluml K, Mutschler E, and Wess J (1994) Functional role of a cytoplasmic aromatic amino acid in muscarinic receptor-mediated activation of phospholipase C. J Biol Chem 269:11537-11541.
8. Boyd GW, Doward AI, Kirkness EF, Millar NS, and Connolly CN (2003) Cell surface expression of 5-hydroxytryptamine type 3 receptors is controlled by an endoplasmic reticulum retention signal. J Biol Chem 278:27681-27687.
9. Braun T, Schofield PR, and Sprengel R (1991) Amino-terminal leucine-rich repeats in gonadotropin receptors determine hormone selectivity. EMBO (Eur Mol Biol Organ) J 10:1885-1890.
10. Brauner-Osborne H, Jensen AA, Sheppard PO, Brodin B, Krogsgaard-Larsen P, and O'Hara P (2001) Cloning and characterization of a human orphan family C G-protein coupled receptor GPRC5D. Biochim Biophys Acta 1518:237-248.
11. Cadigan KM (2002) Wnt signaling-20 years and counting. Trends Genet 18:340-342.
12. Cadigan KM and Nusse R (1997) Wnt signaling: a common theme in animal development. Genes Dev 11:3286-3305.
13. Calver AR, Robbins MJ, Cosio C, Rice SQ, Babbs AJ, Hirst WD, Boyfield I, Wood MD, Russell RB, Price GW, et al. (2001) The C-terminal domains of the GABA(b) receptor subunits mediate intracellular trafficking but are not required for receptor signaling. J Neurosci 21:1203-1210.
14. Chen S, Lin F, Iismaa S, Lee KN, Birckbichler PJ, and Graham RM (1996) α1-adrenergic receptor signaling via Gh is subtype specific and independent of its transglutaminase activity. J Biol Chem 271:32385-32391.
15. Choudhary MS, Craigo S, and Roth BL (1992) Identification of receptor domains that modify ligand binding to 5-hydroxytryptamine2 and 5-hydroxytryptamine1c serotonin receptors. Mol Pharmacol 42:627-633.
16. Conchon S, Barrault MB, Miserey S, Corvol P, and Clauser E (1997) The C-terminal third intracellular loop of the rat AT1A angiotensin receptor plays a key role in G protein coupling specificity and transduction of the mitogenic signal. J Biol Chem 272:25566-25572.
17. Cotecchia S, Exum S, Caron MG, and Lefkowitz RJ (1990) regions of the Alpha 1-adrenergic receptor involved in coupling to phosphatidylinositol hydrolysis and enhanced sensitivity of biological function. Proc Natl Acad Sci USA 87:2896-2900.
18. Cotecchia S, Ostrowski J, Kjelsberg MA, Caron MG, and Lefkowitz RJ (1992) Discrete amino acid sequences of the α1-adrenergic receptor determine the selectivity of coupling to phosphatidylinositol hydrolysis. J Biol Chem 267:1633-1639.
19. Cypess AM, Unson CG, Wu CR, and Sakmar TP (1999) Two cytoplasmic loops of the glucagon receptor are required to elevate cAMP or intracellular calcium. J Biol Chem 274:19455-19464.
20. 2)-adrenergic receptor chimera: pharmacological properties of a unique G protein-linked receptor. Naunyn Schmiedeberg's Arch Pharmacol 365:341-348.
21. Dias JA, Zhang Y, and Liu X (1994) Receptor binding and functional properties of chimeric human follitropin prepared by an exchange between a small hydrophilic intercysteine loop of human follitropin and human lutropin. J Biol Chem 269: 25289-25294.
22. Dixon RA, Sigal IS, Rands E, Register RB, Candelore MR, Blake AD, Strader CD (1987) Ligand binding to the beta-adrenergic receptor involves its rhodopsin-like core. Nature (Lond) 326:73-77.
23. Eason MG and Liggett SB (1995) Identification of a Gs coupling domain in the amino terminus of the third intracellular loop of the α2A-adrenergic receptor. Evidence for distinct structural determinants that confer Gs versus Gi coupling. J Biol Chem 270:24753-24760.
24. Eason MG and Liggett SB (1996) Chimeric mutagenesis of putative G-protein coupling domains of the α2A-adrenergic receptor. Localization of two redundant and fully competent Gi coupling domains. J Biol Chem 271:12826-12832.
25. England BP, Ackerman MS, and Barrett RW (1991) A chimeric D2 dopamin/M1 muscarinic receptor with D2 binding specificity mobilizes intracellular calcium in response to dopamine. FEBS Lett 279:87-90.
26. 2+. Proc Natl Acad Sci USA 89:509-513.
27. Feng YH and Karnik SS (1999) Role of transmembrane helix IV in G-protein specificity of the angiotensin II type 1 receptor. J Biol Chem 274:35546-35552.
28. Flor PJ, Gomeza J, Tones MA, Kuhn R, Pin JP, and Knopfel T (1996) The C-terminal domain of the mGluR1 metabotropic glutamate receptor affects sensitivity to agonists. J Neurochem 67:58-63.
29. Frielle T, Daniel KW, Caron MG, and Lefkowitz RJ (1988) Structural basis of beta-adrenergic receptor subtype specificity studied with chimeric beta 1/beta 2-adrenergic receptors. Proc Natl Acad Sci USA 85:9494-9498
30. Galvez T, Duthey B, Kniazeff J, Blahos J, Rovelli G, Bettler B, Prezeau L, and Pin JP (2001) Allosteric interactions between GB1 and GB2 subunits are required for optimal GABA(B) receptor function. EMBO (Eur Mol Biol Organ) J 20:2152-2159.
31. Gomeza J, Joly C, Kuhn R, Knopfel T, Bockaert J, and Pin JP (1996) The second intracellular loop of metabotropic glutamate receptor 1 cooperates with the other intracellular domains to control coupling to G-proteins. J Biol Chem 271:2199-2205.
32. Green SA, Spasoff AP, Coleman RA, Johnson M, and Liggett SB (1996) Sustained activation of a G protein-coupled receptor via "anchored" agonist binding. Molecular localization of the salmeterol exosite within the 2-adrenergic receptor. J Biol Chem 271:24029-24035.
33. Guan XM, Amend A, and Strader CD (1995) Determination of structural domains for G protein coupling and ligand binding in β 3-adrenergic receptor. Mol Pharmacol 48:492-498.
34. Gupte J, Cutler G, Chen JL, and Tian H (2004) Elucidation of signaling properties of vasopressin receptor-related receptor 1 by using the chimeric receptor approach. Proc Natl Acad Sci USA 101:1508-1513.
35. Hamaguchi N, True TA, Goetz AS, Stouffer MJ, Lybrand TP, and Jeffs PW (1998) Alpha 1-adrenergic receptor subtype determinants for 4-piperidyl oxazole antagonists. Biochemistry 37:5730-5737.
36. Hamaguchi N, True TA, Saussy DL Jr, and Jeffs PW (1996) Phenylalanine in the second membrane-spanning domain of alpha 1α-adrenergic receptor determines subtype selectivity of dihydropyridine antagonists. Biochemistry 35:14312-14317.
37. 2+ receptors. Mol Pharmacol 55:642-648.
38. Hanyaloglu AC, Vrecl M, Kroeger KM, Miles LE, Qian H, Thomas WG, and Eidne KA (2001) Casein kinase II sites in the intracellular C-terminal domain of the thyrotropin-releasing hormone receptor and chimeric gonadotropin-releasing hormone receptors contribute to β -arrestin-dependent internalization. J Biol Chem 276: 18066-18074.
39. Hargrave PA and McDowell JH (1992) Rhodopsin and phototransduction: a model system for G protein-linked receptors. FASEB J 6:2323-2331.
40. Havlickova M, Blahos J, Brabet I, Liu J, Hruskova B, Prezeau L, and Pin JP (2003) The second intracellular loop of metabotropic glutamate receptors recognizes C termini of G-protein α-subunits. J Biol Chem 278:35063-35070.
41. Havlickova M, Prezeau L, Duthey B, Bettler B, Pin JP, and Blahos J (2002) The intracellular loops of the GB2 Subunit are crucial for G-protein coupling of the heteromeric γ-aminobutyrate b receptor. Mol Pharmacol 62:343-350.
42. Hebert TE and Bouvier M (1998) Structural and functional aspects of G protein-coupled receptor oligomerization. Biochem Cell Biol 76:1-11.
43. Heding A, Vrecl M, Bogerd J, McGregor A, Sellar R, Taylor PL, and Eidne KA (1998) Gonadotropin-releasing hormone receptors with intracellular carboxyl-terminal tails undergo acute desensitization of total inositol phosphate production and exhibit accelerated internalization kinetics. J Biol Chem 273:11472-11477.
44. Hicke L, Zanolari B, and Riezman H (1998) Cytoplasmic tail phosphorylation of the alpha-factor receptor is required for its ubiquitination and internalization. J Cell Biol 141:349-358.
45. Hirsch B, Kudo M, Naro F, Conti M, and Hsueh AJ (1996) The C-terminal third of the human luteinizing hormone (LH) receptor is important for inositol phosphate release: analysis using chimeric human LH/follicle-stimulating hormone receptors. Mol Endocrinol 10:1127-1137.
46. Ilani T, Fishburn CS, Levavi-Sivan B, Carmon S, Raveh L, and Fuchs S (2002) Coupling of dopamine receptors to G Proteins: studies with chimeric D2/ D3 dopamine receptors. Cell Mol Neurobiol 22:47-56.
47. 2+ pathway to antagonize Wnt/beta-catenin signaling. Mol Cell Biol 23:131-139.
48. Jewell-Motz EA, Donnelly ET, Eason MG, and Liggett SB (1997) Role of the amino terminus of the third intracellular loop in agonist-promoted downregulation of the alpha2a-adrenergic receptor. Biochemistry 36:8858-8863.
49. Jewell-Motz EA, Donnelly ET, Eason MG, and Liggett SB (1998) Agonist-mediated downregulation of G alpha i via the alpha 2-adrenergic receptor is targeted by receptor-Gi interaction and is independent of receptor signaling and regulation. Biochemistry 37:15720-15725.
50. Jewell-Motz EA, Small KM, Theiss CT, and Liggett SB (2000) α2A/α2C-adrenergic receptor third loop chimera show that agonist interaction with receptor subtype backbone establishes G protein-coupled receptor kinase phosphorylation. J Biol Chem 275:28989-28993.
51. Jockers R, Da Silva A, Strosberg AD, Bouvier M, and Marullo S (1996) New Molecular and structural determinants involved in β2-adrenergic receptor desensitization and sequestration. Delineation using chimeric β3/β2-adrenergic receptors. J Biol Chem 271:9355-9362.
52. 2-selective ligands. Mol Pharmacol 56:1280-1287.
53. Kazmi MA, Snyder LA, Cypess AM, Graber SG, and Sakmar TP (2000) Selective reconstitution of human D4 dopamine receptor variants with Gi alpha subtypes. Biochemistry 39:3734-3744.
54. Kelley SP, Dunlop JI, Kirkness EF, Lambert JJ, and Peters JA (2003) A cytoplasmic region determines single-channel conductance in 5-HT3 receptors. Nature (Lond) 424:321-324.
55. Kikkawa H, Isogaya M, Nagao T, and Kurose H (1998) The role of the seventh transmembrane region in high affinity binding of a β2-Selective agonist TA-2005. Mol Pharmacol 53:128-134.
56. Kobilka BK, Kobilka TS, Daniel K, Regan JW, Caron MG, and Lefkowitz RJ (1988) Chimeric alpha 2-,beta 2-adrenergic receptors: delineation of domains involved in effector coupling and ligand binding specificity. Science (Wash DC) 240:1310-1316.
57. Kozell LB, Machida CA, Neve RL, and Neve KA (1994) Chimeric D1/D2 dopamine receptors. Distinct determinants of selective efficacy, potency and signal transduction. J Biol Chem 269:30299-30306.
58. Kozell LB and Neve KA (1997) Constitutive activity of a chimeric D2/D1 dopamine receptor. Mol Pharmacol 52:1137-1149.
59. Kubo T, Bujo H, Akiba I, Nakai J, Mishina M, and Numa S (1988) Location of a region of the muscarinic acetylcholine receptor involved in selective effector coupling. FEBS Lett 241:119-125.
60. Kudo M, Osuga Y, Kobilka BK, and Hsueh AJ (1996) Transmembrane regions V and VI of the human luteinizing hormone receptor are required for constitutive activation by a mutation in the third intracellular loop. J Biol Chem 271:22470-22478.
61. Lachowicz JE and Sibley DR (1997) Chimeric D2/D3 dopamine receptor coupling to adenylyl cyclase. Biochem Biophys Res Commun 237:394-399.
62. Lai J, Nunan L, Waite SL, Ma SW, Bloom JW, Roeske WR, and Yamamura HI (1992) Chimeric M1/M2 muscarinic receptors: correlation of ligand selectivity and functional coupling with structural modifications. J Pharmacol Exp Ther 262:173-180.
63. Langer I, Vertongen P, Perret J, Waelbroeck M, and Robberecht P (2002) A small sequence in the third intracellular loop of the VPAC(1) receptor is responsible for its efficient coupling to the calcium effector. Mol Endocrinol 16:1089-1096.
64. Lapinsh M, Prusis P, Gutcaits A, Lundstedt T, and Wikberg JE (2001) Development of proteo-chemometrics: a novel technology for the analysis of drug-receptor interactions. Biochim Biophys Acta 1525:180-190.
65. Lefkowitz RJ (1998) G Protein-coupled receptors. III. New roles for receptor kinases and β-arrestins in receptor signaling and desensitization. J Biol Chem 273:18677-18680.
66. Li H, Malbon CC, and Wang HY (2004) Gene profiling of Frizzled-1 and Frizzled-2 signaling: expression of G-protein-coupled receptor chimeras in mouse F9 teratocarcinoma embryonal cells. Mol Pharmacol 65:45-55.
67. Liggett SB, Freedman NJ, Schwinn DA, and Lefkowitz RJ (1993) Structural basis for receptor subtype-specific regulation revealed by a chimeric beta 3/beta 2-adrenergic receptor. Proc Natl Acad Sci USA 90:3665-3669.
68. Liu T, DeCostanzo AJ, Liu X, Wang H, Hallagan S, Moon RT, and Malbon CC (2001) G protein signaling from activated rat frizzled-1 to the beta-catenin-Lef-Tcf pathway. Science (Wash DC) 292:1718-1722.
69. o function. J Biol Chem 274:33539-33544.
70. Liu X, Liu T, Slusarski DC, Yang-Snyder J, Malbon CC, Moon RT, and Wang H (1999b) Activation of a frizzled-2/beta-adrenergic receptor chimera promotes wnt signaling and differentiation of mouse F9 teratocarcinoma cells via Galphao and Galphat. Proc Natl Acad Sci USA 96:14383-14388.
71. MacKenzie RG, Steffey ME, ManeUi AM, Pollock NJ, and Frail DE (1993) A D1/D2 chimeric dopamine receptor mediates a D1 response to a D2-selective agonist. FEBS Lett 323:59-62.
72. Maggio R, Barbier P, Colelli A, Salvadori F, Demontis G, and Corsini GU (1999) G protein-linked receptors: pharmacological evidence for the formation of heterodimers. J Pharmacol Exp Ther 291:251-257.
73. Maggio R, Vogel Z, and Wess J (1993) Coexpression studies with mutant muscarinic/adrenergic receptors provide evidence for intermolecular "cross-talk" between G-protein-linked receptors. Proc Natl Acad Sci USA 90:3103-3107.
74. Malbon CC, Wang H, and Moon RT (2001) Wnt signaling and heterotrimeric G-proteins: strange bedfellows or a classic romance? Biochem Biophys Res Commun 287:589-593.
75. B receptors is sufficient to specify agonist and antagonist binding. Mol Pharmacol 56:448-454.
76. Margeta-Mitrovic M, Jan YN, and Jan LY (2001a) Function of GB1 and GB2 subunits in G protein coupling of GABA(B) receptors. Proc Natl Acad Sci USA 98:14649-14654.
77. Margeta-Mitrovic M, Jan YN, and Jan LY (2001b) Ligand-induced signal transduction within heterodimeric GABA(B) receptor. Proc Natl Acad Sci USA 98:14643-14648.
78. Marin EP, Krishna AG, Zvyaga TA, Isele J, Siebert F, and Sakmar TP (2000) The amino terminus of the fourth cytoplasmic loop of rhodopsin modulates rhodopsin-transducin interaction. J Biol Chem 275:1930-1936.
79. Marullo S, Emorine LJ, Strosberg AD, and Delavier-Klutchko C (1990) Selective binding of ligands to beta 1, beta 2 or chimeric beta 1/beta 2-adrenergic receptors involves multiple subsites. EMBO (Eur Mol Biol Organ) J 9:1471-1476.
80. McAllister G, Knowles MR, Patel S, Marwood R, Emms F, Seabrook GR, Graziano M, Borkowski D, Hey PJ, and Freedman SB (1993) Characterisation of a chimeric HD3/D2 dopamine receptor expressed in CHO cells. FEBS Lett 324:81-86.
81. Morris AJ and Malbon CC (1999) Physiological regulation of G protein-linked signaling. Physiol Rev 79:1373-1430.
82. Mostafapour S, Kobilka BK, and von Zastrow M (1996) Pharmacological sequestration of a chimeric beta 3/beta 2 adrenergic receptor occurs without a corresponding amount of receptor internalization. Recept Signal Transduct 6:151-163.
83. Nagayama Y, Chazenbalk GD, Takeshita A, Kimura H, Ashizawa K, Yokoyama N, Rapoport B, and Nagataki S (1994) Studies on homologous desensitization of the thyrotropin receptor in 293 human embryonal kidney cells. Endocrinology 135: 1060-1065.
84. Nagayama Y, Russo D, Chazenbalk GD, Wadsworth HL, and Rapoport B (1990) Extracellular domain chimeras of the TSH and LH/CG receptors reveal the midregion (amino acids 171-260) to play a vital role in high affinity TSH binding. Biochem Biophys Res Commun 173:1150-1156.
85. Nagayama Y, Wadsworth HL, Russo D, Chazenbalk GD, and Rapoport B (1991) Binding domains of stimulatory and inhibitory thyrotropin (TSH) receptor autoantibodies determined with chimeric TSH-lutropin/chorionic gonadotropin receptors. J Clin Investig 88:336-340.
86. Nantel F, Bonin H, Emorine LJ, Zilberfarb V, Strosberg AD, Bouvier M, and Marullo S (1993) The human β3-adrenergic receptor is resistant to short term agonist-promoted desensitization. Mol Pharmacol 43:548-555.
87. Oakley RH, Laporte SA, Holt JA, Barak LS, and Caron MG (1999) Association of β-arrestin with G protein-coupled receptors during clathrin-mediated endocytosis dictates the profile of receptor resensitization. J Biol Chem 274:32248-32257.
88. Oksenberg D, Havlik S, Peroutka SJ, and Ashkenazi A (1995) The third intracellular loop of the 5-hydroxytryptamine2a receptor determines effector coupling specificity. J Neurochem 64:1440-1447.
89. Osuga Y, Hayashi M, Kudo M, Conti M, Kobilka B, and Hsueh AJ (1997) Coexpression of defective luteinizing hormone receptor fragments partially reconstitutes ligand-induced signal generation. J Biol Chem 272:25006-25012.
90. Parker EM, Izzarelli DG, Lewis-Higgins L, Palmer D, and Shapiro RA (1996) Two amino acid differences in the sixth transmembrane domain are partially responsible for the pharmacological differences between the 5-HT1D beta and 5-HT1E 5-hydroxytryptamine receptors. J Neurochem 67:2096-2103.
91. Parker EM, Swigart P, Nunnally MH, Perkins JP, and Ross EM (1995) Carboxyl-terminal domains in the avian β1-adrenergic receptor that regulate agonist-promoted endocytosis. J Biol Chem 270:6482-6487.
92. Pin JP, Joly C, Heinemann SF, and Bockaert J (1994) Domains involved in the specificity of G protein activation in phospholipase C-coupled metabotropic glutamate receptors. EMBO (Eur Mol Biol Organ) J 13:342-348.
93. Pittel Z and Wess J (1994) Intramolecular interactions in muscarinic acetylcholine receptors studied with chimeric M2/M5 receptors. Mol Pharmacol 45:61-64.
94. Robbins MJ, Calver AR, Filippov AK, Hirst WD, Russell RB, Wood MD, Nasir S, Couve A, Brown DA, Moss SJ, et al. (2001) GABA(B2) is essential for G-protein coupling of the GABA(B) receptor heterodimer. J Neurosci 21:8043-8052.
95. Robinson SW and Caron MG (1996) Chimeric D2/D3 dopamine receptors efficiently inhibit adenylyl cyclase in HEK 293 cells. J Neurochem 67:212-219.
96. Robinson SW, Jarvie KR, and Caron MG (1994) High affinity agonist binding to the dopamine D3 receptor: chimeric receptors delineate a role for intracellular domains. Mol Pharmacol 46:352-356.
97. Rousseau G, Nantel F, and Bouvier M (1996) Distinct receptor domains determine subtype-specific coupling and desensitization phenotypes for human β1- and β2-adrenergic receptors. Mol Pharmacol 49:752-760.
98. Sambrano GR and Coughlin SR (1999) The carboxyl tail of protease-activated receptor-1 is required for chemotaxis. Correlation of signal termination and directional migration. J Biol Chem 274:20178-20184.
99. Saunders C, Keefer JR, Bonner CA, and Limbird LE (1998) Targeting of G protein-coupled receptors to the basolateral surface of polarized renal epithelial cells involves multiple, non-contiguous structural signals. J Biol Chem 273:24196-24206.
100. Scarselli M, Novi F, Schallmach E, Lin R, Baragli A, Colzi A, Griffon N, Corsini GU, Sokoloff P, Levenson R, et al. (2001) D2/D3 dopamine receptor heterodimers exhibit unique functional properties. J Biol Chem 276:30308-30314.
101. Shaaban S and Benton B (2001) Orphan G protein-coupled receptors: from DNA to drug targets. Curr Opin Drug Discov Devel 4:535-547.
102. Shenoy SK, McDonald PH, Kohout TA, and Lefkowitz RJ (2001) Regulation of receptor fate by ubiquitination of activated beta 2-adrenergic receptor and beta-arrestin. Science (Wash DC) 294:1307-1313.
103. Shih YH, Chung FZ, and Pugsley TA (1997) Cloning, expression and characterization of a human dopamine D4.2 receptor (CHO K1 Cells) and various D4.2/D2L chimeras (COS-7 cells). Prog Neuropsychopharmacol Biol Psychiatry 21:153-167.
104. Shiina T, Kawasaki A, Nagao T, and Kurose H (2000) Interaction with β-arrestin determines the difference in internalization behavor between β1- and β2-adrenergic receptors. J Biol Chem 275:29082-29090.
105. Shinoura H, Shibata K, Hirasawa A, Tanoue A, Hashimoto K, and Tsujimoto G (2002) Key amino acids for differential coupling of alpha1-adrenergic receptor subtypes to Gs. Biochem Biophys Res Commun 299:142-147.
106. Shumay E, Song X, Wang HY, and Malbon CC (2002) Pp60Src mediates insulin-stimulated sequestration of the beta(2)-adrenergic receptor: insulin stimulates Pp60Src phosphorylation and activation. Mol Biol Cell 13:3943-3954.
107. 2+ signaling by Wnt-5A. Dev Biol 182:114-120.
108. Snyder M (1989) The SPA2 protein of yeast localizes to sites of cell growth. J Cell Biol 108:1419-1429.
109. 1-selective binding in resting and active states. J Pharmacol Exp Ther 301:51-58.
110. Swain RK, Medina A, and Steinbeisser H (2001) Functional analysis of the Xenopus frizzled 7 protein domains using chimeric receptors. Int J Dev Biol 45:259-264.
111. Tohgo A, Choy EW, Gesty-Palmer D, Pierce KL, Laporte S, Oakley RH, Caron MG, Lefkowitz RJ, and Luttrell LM (2003) The stability of the G protein-coupled receptor-β-arrestin interaction determines the mechanism and functional consequence of ERK activation. J Biol Chem 278:6258-6267.
112. Tota MR and Strader CD (1990) Characterization of the binding domain of the β-adrenergic receptor with the fluorescent antagonist carazolol. Evidence for a buried ligand binding site. J Biol Chem 265:16891-16897.
113. Trejo J and Coughlin SR (1999) The cytoplasmic tails of protease-activated receptor-1 and substance P receptor specify sorting to lysosomes versus recycling. J Biol Chem 274:2216-2224.
114. Trejo J, Hammes SR, and Coughlin SR (1998) Termination of signaling by protease-activated receptor-1 is linked to lysosomal sorting. Proc Natl Acad Sci USA 95:13698-13702.
115. Van Leeuwen DH, Eisenstein J, O'Malley K, and MacKenzie RG (1995) Characterization of a chimeric human dopamine D3/D2 receptor functionally coupled to adenylyl cyclase in chinese hamster ovary cells. Mol Pharmacol 48:344-351.
116. 1a-adrenergic receptors. Functional aspects. J Biol Chem 275:6553-6559.
117. Verrall S, Ishii M, Chen M, Wang L, Tram T, and Coughlin SR (1997) The thrombin receptor second cytoplasmic loop confers coupling to Gq-like G proteins in chimeric receptors. Additional evidence for a common transmembrane signaling and G protein coupling mechanism in G protein-coupled receptors. J Biol Chem 272: 6898-6902.
118. Vischer HF, Granneman JC, Noordam MJ, Mosselman S, and Bogerd J (2003) Ligand selectivity of gonadotropin receptors. Role of the β-strands of extracellular leucine-rich repeats 3 and 6 of the human luteinizing hormone receptor. J Biol Chem 278:15505-15513.
119. Vouret-Craviari V, Auberger P, Pouyssegur J, and Obberghen-Schilling E (1995) Distinct mechanisms regulate 5-HT2 and thrombin receptor desensitization. J Biol Chem 270:4813-4821.
120. 2+ and cyclic GMP: visualizing frizzled functions. Science (Wash DC) 300:1529-1531.
121. Wang LD, Gantz I, Butler K, Hoeltzel M, and Del Valle J (2000) Histamine H2 receptor mediated dual signaling: mapping of structural requirements using beta2 adrenergic chimeric receptors. Biochem Biophys Res Commun 276:539-545.
122. Wess J (1998) Molecular basis of receptor/G-protein-coupling selectivity. Pharmacol Ther 80:231-264.
123. Wess J, Bonner TI, and Brann MR (1990a) Chimeric M2/M3 Muscarinic receptors: role of carboxyl terminal receptor domains in selectivity of ligand binding and coupling to phosphoinositide hydrolysis. Mol Pharmacol 38:872-877.
124. Wess J, Bonner TI, Dorje F, and Brann MR (1990b) Delineation of muscarinic receptor domains conferring selectivity of coupling to guanine nucleotide-binding proteins and second messengers. Mol Pharmacol 38:517-523.
125. Wess J, Brann MR, and Bonner TI (1989) Identification of a small intracellular region of the muscarinic M3 receptor as a determinant of selective coupling to PI turnover. FEBS Lett 258:133-136.
126. Wess J, Gdula D, and Brann MR (1992) Structural basis of the subtype selectivity of muscarinic antagonists: a study with chimeric M2/M5 muscarinic receptors. Mol Pharmacol 41:369-374.
127. Willert K, Brown JD, Danenberg E, Duncan AW, Weissman IL, Reya T, Yates JR, and Nusse R (2003) Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature (Lond) 423:448-452.
128. Wong SK, Parker EM, and Ross EM (1990) Chimeric muscarinic cholinergic: β-adrenergic receptors that activate gs in response to muscarinic agonists. J Biol Chemi 265:6219-6224.
129. Wurch T, Colpaert FC, and Pauwels PJ (1998) Chimeric receptor analysis of the ketanserin binding site in the human 5-hydroxytryptamine1D receptor: importance of the second extracellular loop and fifth transmembrane domain in antagonist binding. Mol Pharmacol 54:1088-1096.
130. Yamashita T, Terakita A, and Shichida Y (2001) The Second cytoplasmic loop of metabotropic glutamate receptor functions at the third loop position of rhodopsin. J Biochem (Tokyo) 130:149-155.
131. Yarden Y, Rodriguez H, Wong SK, Brandt DR, May DC, Burnier J, Harkins RN, Chen EY, Ramachandran J, and Ullrich A (1986) The Avian beta-adrenergic receptor: primary structure and membrane topology. Proc Natl Acad Sci USA 83:6795-6799.
132. Zhao MM, Gaivin RJ, and Perez DM (1998) The third extracellular loop of the β2-adrenergic receptor can modulate receptor/G protein affinity. Mol Pharmacol 53:524-529.
133. Zhao MM, Hwa J, and Perez DM (1996) Identification of critical Extracellular loop residues involved in al-adrenergic receptor subtype-selective antagonist binding. Mol Pharmacol 50:1118-1126.