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Titolo:
Characterization of Agouti-related protein binding to melanocortin receptors
Autore:
Yang, YK; Thompson, DA; Dickinson, CJ; Wilken, J; Barsh, GS; Kent, SBH; Gantz, I;
Indirizzi:
Univ Michigan, Med Ctr, Dept Surg, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 , Dept Surg, Ann Arbor, MI 48109 USA Univ Michigan, Med Ctr, Dept Pediat, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 Dept Pediat, Ann Arbor, MI 48109 USA Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA Stanford Univ Stanford CA USA 94305 ghes Med Inst, Stanford, CA 94305 USA Gryphon Sci, S San Francisco, CA 94080 USA Gryphon Sci S San Francisco CAUSA 94080 i, S San Francisco, CA 94080 USA
Titolo Testata:
MOLECULAR ENDOCRINOLOGY
fascicolo: 1, volume: 13, anno: 1999,
pagine: 148 - 155
SICI:
0888-8809(199901)13:1<148:COAPBT>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
MELANOCYTE-STIMULATING-HORMONE; IN-VITRO; LOCALIZATION; EXPRESSION; ANTAGONIST; OBESITY; CELLS; MICE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
26
Recensione:
Indirizzi per estratti:
Indirizzo: Gantz, I 6504 MSRB 1,1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA 6504 MSRB1,1150 W Med Ctr Dr Ann Arbor MI USA 48109 I 48109 USA
Citazione:
Y.K. Yang et al., "Characterization of Agouti-related protein binding to melanocortin receptors", MOL ENDOCR, 13(1), 1999, pp. 148-155

Abstract

Agouti-related protein (AGRP) is a naturally occurring antagonist of melanocortin action that is thought to play an important role in the hypothalamic control of feeding behavior. The exact mechanism of AGRP and Agouti protein action has been difficult to examine, in part because of difficulties inproducing homogeneous forms of these molecules that can be used for directbinding assays. In this report we describe the application of chemical protein synthesis to the construction of two novel AGRP variants. Examination of the biological activity of the AGRP variants demonstrates that a truncated variant, human AGRP(87-132), a 46-amino acid variant based on the carboxyl-terminal cysteine-rich domain of AGRP, is equipotent to an 111-amino acid variant, mouse [Leu127Pro]AGRP (mature AGRP minus its signal sequence), in its ability to dose dependently inhibit alpha-MSH-generated cAMP generation at the cloned melanocortin receptors. Furthermore, deletion of the amino-terminal portion of the full-length variant did not alter the MCR subtype specificity of AGRP(87-132). Finally, iodination of human AGRP(87-132) provided a useful reagent with which the binding properties of AGRP could be analyzed. In both conventional and photoemulsion binding studies [I-125]AGRP(87-132) was observed only to bind to cells expressing melanocortin receptors MC3R, MC4R, and MC5R. These results demonstrate that the residues critical for receptor binding, alpha-MSH inhibition, and melanocortin receptor subtype specificity are all located in the carboxyl terminus of the molecule. Because [Nle(4), D-Phe(7)] (NDP)-MSH displaces the binding of [I-125]AGRP(87-132) to MCRs and AGRP(87-132) displaces the binding of [I-125]NDP-MSH, weconclude that these molecules bind in a competitive fashion to melanocortin receptors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/09/20 alle ore 13:39:23