Constitutively active mutants of the β1-adrenergic receptor

被引：42

作者：

Lattion, AL ^{[1
]}

Abuin, L ^{[1
]}

Nenniger-Tosato, M ^{[1
]}

Cotecchia, S ^{[1
]}

机构：

[1] Univ Lausanne, Inst Pharmacol & Toxicol, CH-1005 Lausanne, Switzerland

来源：

FEBS LETTERS | 1999年 / 457卷 / 03期

关键词：

G protein-coupled receptor; adrenergic receptor; constitutive activity; inverse agonism;

D O I：

10.1016/S0014-5793(99)01064-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We provide the first evidence that point mutations can constitutively activate the beta(1)-adrenergic receptor (AR), Leucine 322 of the Pi-AR in the C-terminal portion of its third intracellular loop was replaced,vith seven amino acids CI, T, E, F, C, A and K) differing in their physico-chemical properties. The beta(1)-AR mutants expressed in HEK-293 cells displayed various levels of constitutive activity which could be partially inhibited by some beta-blockers. The results of this study might have interesting implications for future studies aiming at elucidating the activation process of the beta(1)-AR as well as the mechanism of action of beta-blockers. (C) 1999 Federation of European Biochemical Societies.

引用

页码：302 / 306

页数：5

共 16 条

[1] PHYSIOLOGICAL-EFFECTS OF INVERSE AGONISTS IN TRANSGENIC MICE WITH MYOCARDIAL OVEREXPRESSION OF THE BETA(2)-ADRENOCEPTOR [J].

BOND, RA ;

LEFF, P ;

JOHNSON, TD ;

MILANO, CA ;

ROCKMAN, HA ;

MCMINN, TR ;

APPARSUNDARAM, S ;

HYEK, MF ;

KENAKIN, TP ;

ALLEN, LF ;

LEFKOWITZ, RJ .

NATURE, 1995, 374 (6519) :272-276

[2]

Chidiac P, 1996, MOL PHARMACOL, V50, P662

[3]

CHIDIAC P, 1994, MOL PHARMACOL, V45, P490

[4] CLONING OF THE CDNA FOR THE HUMAN BETA-1-ADRENERGIC RECEPTOR [J].

FRIELLE, T ;

COLLINS, S ;

DANIEL, KW ;

CARON, MG ;

LEFKOWITZ, RJ ;

KOBILKA, BK .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (22) :7920-7924

[5]

GREEN SA, 1992, MOL PHARMACOL, V41, P889

[6]

KJELSBERG MA, 1992, J BIOL CHEM, V267, P1430

[7] EFFICACY OF BETA-1-ADRENERGIC RECEPTORS IS LOWER THAN THAT OF BETA-2-ADRENERGIC RECEPTORS [J].

LEVY, FO ;

ZHU, X ;

KAUMANN, AJ ;

BIRNBAUMER, L .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (22) :10798-10802

[8]

MacEwan DJ, 1996, MOL PHARMACOL, V50, P1479

[9] ACTIVATION OF CALCIUM CURRENTS IN CARDIAC MYOCYTES BY EMPTY BETA-ADRENOCEPTORS [J].

MEWES, T ;

DUTZ, S ;

RAVENS, U ;

JAKOBS, KH .

CIRCULATION, 1993, 88 (06) :2916-2922

[10] INVERSE AGONISM - PHARMACOLOGICAL CURIOSITY OR POTENTIAL THERAPEUTIC STRATEGY [J].

MILLIGAN, G ;

BOND, RA ;

LEE, M .

TRENDS IN PHARMACOLOGICAL SCIENCES, 1995, 16 (01) :10-13

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