Constitutively active G protein-coupled receptor mutants: Implications on receptor function and drug action

被引:12
作者
Cotecchia, S
Fanelli, F
Costa, T
机构
[1] Univ Lausanne, Inst Pharmacol & Toxicol, CH-1005 Lausanne, Switzerland
[2] Univ Modena & Reggio Emilia, Dulbecco Telethon Inst, Modena, Italy
[3] Univ Modena & Reggio Emilia, Dept Chem, Modena, Italy
[4] Ist Super Sanita, I-00161 Rome, Italy
关键词
D O I
10.1089/15406580360545125
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Mutations of GPCRs can increase their constitutive (agonist-independent) activity. Some of these mutations have been artificially introduced by site-directed mutagenesis; others occur spontaneously in human diseases. The analysis of constitutively active GPCR mutants has attracted a large interest in the past decade, providing an important contribution to our understanding of the molecular mechanisms underlying receptor function and drug action.
引用
收藏
页码:311 / 316
页数:6
相关论文
共 29 条
[11]   Mutagenesis and modelling of the α1b-adrenergic receptor highlight the role of the helix 3/helix 6 interface in receptor activation [J].
Greasley, PJ ;
Fanelli, F ;
Rossier, O ;
Abuin, L ;
Cotecchia, S .
MOLECULAR PHARMACOLOGY, 2002, 61 (05) :1025-1032
[12]  
HOGGER P, 1995, J BIOL CHEM, V270, P7405
[13]   Efficacy at G-protein-coupled receptors [J].
Kenakin, T .
NATURE REVIEWS DRUG DISCOVERY, 2002, 1 (02) :103-110
[14]  
KJELSBERG MA, 1992, J BIOL CHEM, V267, P1430
[15]   Inverse agonism and the regulation of receptor number [J].
Milligan, G ;
Bond, RA .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1997, 18 (12) :468-474
[16]   INVERSE AGONISM - PHARMACOLOGICAL CURIOSITY OR POTENTIAL THERAPEUTIC STRATEGY [J].
MILLIGAN, G ;
BOND, RA ;
LEE, M .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1995, 16 (01) :10-13
[17]   Crystal structure of rhodopsin: A G protein-coupled receptor [J].
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 .
SCIENCE, 2000, 289 (5480) :739-745
[18]   SOMATIC MUTATIONS IN THE THYROTROPIN RECEPTOR GENE CAUSE HYPERFUNCTIONING THYROID ADENOMAS [J].
PARMA, J ;
DUPREZ, L ;
VANSANDE, J ;
COCHAUX, P ;
GERVY, C ;
MOCKEL, J ;
DUMONT, J ;
VASSART, G .
NATURE, 1993, 365 (6447) :649-651
[19]   Lessons from constitutively active mutants of G protein-coupled receptors [J].
Parnot, C ;
Miserey-Lenkei, S ;
Bardin, S ;
Corvol, P ;
Clauser, E .
TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2002, 13 (08) :336-343
[20]   Mutation of a highly conserved aspartic acid in the β2 adrenergic receptor:: Constitutive activation, structural instability, and conformational rearrangement of transmembrane segment 6 [J].
Rasmussen, SGF ;
Jensen, AD ;
Liapakis, G ;
Ghanouni, P ;
Javitch, JA ;
Gether, U .
MOLECULAR PHARMACOLOGY, 1999, 56 (01) :175-184