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Titolo:
Contribution of melanocortin receptor exoloops to Agouti-related protein binding
Autore:
Yang, YK; Dickinson, CJ; Zeng, Q; Li, JY; Thompson, DK; Gantz, I;
Indirizzi:
Univ Michigan, Sch Med, Dept Gen Surg, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 pt Gen Surg, Ann Arbor, MI 48109 USA Ann Arbor Vet Adm Hosp, Dept Gen Surg, Ann Arbor, MI 48109 USA Ann Arbor Vet Adm Hosp Ann Arbor MI USA 48109 rg, Ann Arbor, MI 48109 USA Gryphon Sci, S San Francisco, CA 94080 USA Gryphon Sci S San Francisco CAUSA 94080 i, S San Francisco, CA 94080 USA Univ Michigan, Sch Med, Dept Pediat, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 Dept Pediat, Ann Arbor, MI 48109 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 20, volume: 274, anno: 1999,
pagine: 14100 - 14106
SICI:
0021-9258(19990514)274:20<14100:COMRET>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
STIMULATING-HORMONE RECEPTOR; MOLECULAR-CLONING; COUPLED RECEPTORS; LIGAND-BINDING; EXPRESSION; ANTAGONISM; OBESITY; FAMILY; MICE; ART;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
23
Recensione:
Indirizzi per estratti:
Indirizzo: Gantz, I 6504 MSRB I,1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA 6504 MSRBI,1150 W Med Ctr Dr Ann Arbor MI USA 48109 I 48109 USA
Citazione:
Y.K. Yang et al., "Contribution of melanocortin receptor exoloops to Agouti-related protein binding", J BIOL CHEM, 274(20), 1999, pp. 14100-14106

Abstract

Agouti-related protein (AGRP) is an endogenous antagonist of melanocortin action that functions in the hypothalamic control of feeding behavior. Although previous studies have shown that AGRP binds three of the five known subtypes of melanocortin receptor, the receptor domains participating in binding and the molecular interactions involved are presently unknown, The present studies were designed to examine the contribution of extracytoplasmic domains of the melanocortin-4 receptor (MC4R) to AGRP binding by making chimerical receptor constructs of the human melanocortin-1 receptor (MC1R; a receptor that is not inhibited by AGRP) and the human MC4R (a receptor that is potently inhibited by AGRP). Substitutions of the extracytoplasmic NH2 terminus and the first extracytoplasmic: loop (exoloop) of the MC4R, with homologous domains of the MC1R had no effect on AGRP (87-132) binding affinityor inhibitory activity (the ability to inhibit melanocortin-stimulated cAMP generation). In contrast, cassette substitutions of exoloops 2 and 3 of the MC4R with the homologous exoloops of the MC1R resulted in a substantial loss of AGRP binding affinity and inhibitory activity. Conversely, the exchange of exoloops 2 land 3 of the MC1R with the homologous exoloops of the MC4R was found to confer AGRP binding and inhibitory activity to the basic structure of the MC1R. Importantly, these substitutions did not affect the ability of the alpha-melanocyte stimulating: hormone analogue [Nle(4),D-Phe(7)] melanocyte stimulating hormone to bind or activate the chimeric receptors. These data indicate that exoloops 2 and 3 of the melanocortin receptorsare important for AGRP binding.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/09/20 alle ore 23:47:45