| First Author | Lu D | Year | 1994 |
| Journal | Nature | Volume | 371 |
| Issue | 6500 | Pages | 799-802 |
| PubMed ID | 7935841 | Mgi Jnum | J:21074 |
| Mgi Id | MGI:69123 | Doi | 10.1038/371799a0 |
| Citation | Lu D, et al. (1994) Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor. Nature 371(6500):799-802 |
| abstractText | The genetic loci agouti and extension control the relative amounts of eumelanin (brown-black) and phaeomelanin (yellow-red) pigments in mammals: extension encodes the receptor for melanocyte-stimulating hormone (MSH) and agouti encodes a novel 131-amino-acid protein containing a signal sequence. Agouti, which is produced in the hair follicle, acts on follicular melanocytes 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, a related MSH-binding receptor. Consequently, the obesity caused by ectopic expression of agouti in the lethal yellow (Ay) mouse may be due to the inhibition of melanocortin receptor(s) outside the hair follicle. |
