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| AGOUTI PROTEIN IS AN ANTAGONIST OF THE MELANOCYTE-STIMULATING-HORMONE RECEPTOR |
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| Author(s): LU DS, WILLARD D, PATEL IR, KADWELL S, OVERTON L, KOST T, LUTHER M, CHEN WB, WOYCHIK RP, WILKISON WO, CONE RD |
| Source: NATURE Volume: 371 Issue: 6500 Pages: 799-802 Published: OCT 27 1994 |
| Times Cited: 625 References: 25 |
| Abstract: THE genetic loci agouti and extension control the relative amounts of eumelanin (brown-black) and phaeomelanin (yellow-red) pigments in mammals(1): extension encodes the receptor for melanocyte-stimulating hormone (MSH)(2) and agouti encodes a novel 131-amino-acid protein containing a signal sequence(3,4). Agouti, which is produced in the hair follicle(5), acts on follicular melanocytes(6) to inhibit alpha-MSH-induced eumelanin production, resulting in the subterminal band of phaeomelanin often visible in mammalian fur. Here we use partially purified agouti protein to demonstrate that agouti is a high-affinity antagonist of the MSH receptor and blocks alpha-MSH stimulation of adenylyl cyclase, the effector through which alpha-MSH induces eumelanin synthesis, Agouti was also found to be an antagonist of the melanocortin-4 receptor(7,8), a related MSH-binding receptor. Consequently, the obesity caused by ectopic expression of agouti in the lethal yellow (A(y)) mouse(9) may be due to the inhibition of melanocortin reteptor(s) outside the hair follicle. |
| Document Type: Article |
| Language: English |
Addresses:
1. GLAXO INC, RES INST, DIV MOLEC SCI, RES TRIANGLE PK, NC 27709 USA
2. OREGON HLTH SCI UNIV, VOLLUM INST ADV BIOMED RES, PORTLAND, OR 97201 USA
3. OAK RIDGE NATL LAB, DIV BIOL, OAK RIDGE, TN 37831 USA |
| Publisher: MACMILLAN MAGAZINES LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: PP018 |
| ISSN: 0028-0836 |
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