Teaching old receptors new tricks: biasing seven-transmembrane receptors

被引：659

作者：

Rajagopal, Sudarshan ^{[1
]}

Rajagopal, Keshava ^{[2
]}

Lefkowitz, Robert J. ^{[1
,3
,4
]}

机构：

[1] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA

[2] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA

[3] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA

[4] Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA

来源：

NATURE REVIEWS DRUG DISCOVERY | 2010年 / 9卷 / 05期

基金：

美国国家卫生研究院;

关键词：

PROTEIN-COUPLED RECEPTOR; BETA-ADRENERGIC-RECEPTOR; LIGHT-DEPENDENT PHOSPHORYLATION; GROWTH-FACTOR RECEPTOR; TERNARY COMPLEX MODEL; ADENYLATE-CYCLASE; DRUG DISCOVERY; BETA(2)-ADRENERGIC RECEPTOR; CONFORMATIONAL-CHANGES; ERK1/2; ACTIVATION;

D O I：

10.1038/nrd3024

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Seven-transmembrane receptors (7TMRs; also known as G protein-coupled receptors) are the largest class of receptors in the human genome and are common targets for therapeutics. Originally identified as mediators of 7TMR desensitization, beta-arrestins (arrestin 2 and arrestin 3) are now recognized as true adaptor proteins that transduce signals to multiple effector pathways. Signalling that is mediated by beta-arrestins has distinct biochemical and functional consequences from those mediated by G proteins, and several biased ligands and receptors have been identified that preferentially signal through either G protein- or beta-arrestin-mediated pathways. These ligands are not only useful tools for investigating the biochemistry of 7TMR signalling, they also have the potential to be developed into new classes of therapeutics.

引用

页码：373 / 386

页数：14

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