Melanocortin receptors form constitutive homo- and heterodimers

被引：63

作者：

Mandrika, I ^{[1
]}

Petrovska, R ^{[1
]}

Wikberg, J ^{[1
]}

机构：

[1] Uppsala Univ, Div Pharmacol, Dept Pharmaceut Biosci, SE-75124 Uppsala, Sweden

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2005年 / 326卷 / 02期

关键词：

melanocortin receptor; dimerization; bioluminescence resonance energy transfer; agonist; antagonist;

D O I：

10.1016/j.bbrc.2004.11.036

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：

A significant number of G protein-coupled receptors are shown to form homo- or heterodimers/oligomers, and oligomerization of GPCRs may be a quite general phenomenon. We have here explored the possibility that the two closely related human melanocortin receptor 1 (MC1R) and melanocortin receptor 3 (MC3R) form dimers. Using bioluminescence resonance energy transfer (BRET2) we demonstrate that MC1 and MC(3)Rs form homo- and heterodimers, when expressed in Cos-7 cells. Treatment with agonist, partial agonist or antagonists did not modify the BRET2 signal for any of the receptor pairs studied, suggesting that the dimerization is not regulated by ligand binding. Rather our results indicate that melanocortin receptors exist as constitutively pre-formed dimers. (C) 2004 Elsevier Inc. All rights reserved.

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页码：349 / 354

页数：6

相关论文

共 24 条

[1] Dimerization: An emerging concept for G protein-coupled receptor ontogeny and function [J].

Angers, S ;

Salahpour, A ;

Bouvier, M .

ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 2002, 42 :409-435

[2] Autosomal-dominant mode of inheritance of a melanocortin-4 receptor mutation in a patient with severe early-onset obesity is due to a dominant-negative effect caused by receptor dimerization [J].

Biebermann, H ;

Krude, H ;

Elsner, A ;

Chubanov, V ;

Gudermann, T ;

Grüters, A .

DIABETES, 2003, 52 (12) :2984-2988

[3]

CAMPBELL MJ, 1995, BIOTECHNIQUES, V18, P1027

[4] Synthesis and characterization of bivalent peptide ligands targeted to G-protein-coupled receptors [J].

Carrithers, MD ;

Lerner, MR .

CHEMISTRY & BIOLOGY, 1996, 3 (07) :537-542

[5] Agonist-dependent dissociation of oligomeric complexes of G protein-coupled cholecystokinin receptors demonstrated in living cells using bioluminescence resonance energy transfer [J].

Cheng, ZJ ;

Miller, LJ .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (51) :48040-48047

[6] Gonadotropin-releasing hormone receptor microaggregation -: Rate monitored by fluorescence resonance energy transfer [J].

Cornea, A ;

Janovick, DA ;

Maya-Núñez, G ;

Conn, PM .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (03) :2153-2158

[7] Dimerization of the delta opioid receptor: Implication for a role in receptor internalization [J].

Cvejic, S ;

Devi, LA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (43) :26959-26964

[8] G-protein-coupled receptor heterodimerization modulates receptor function [J].

Jordan, BA ;

Devi, LA .

NATURE, 1999, 399 (6737) :697-700

[9] Discovery of a novel superpotent and selective melanocortin-4 receptor antagonist (HS024):: Evaluation in vitro and in vivo [J].

Kask, A ;

Mutulis, F ;

Muceniece, R ;

Pähkla, R ;

Mutule, I ;

Wikberg, JES ;

Rägo, L ;

Schiöth, HB .

ENDOCRINOLOGY, 1998, 139 (12) :5006-5014

[10] G-protein coupled receptor oligomerization in neuroendocrine pathways [J].

Kroeger, KM ;

Pfleger, KDG ;

Eidne, KA .

FRONTIERS IN NEUROENDOCRINOLOGY, 2003, 24 (04) :254-278