| 背景 | Melanocortin receptor 4 (MC4R) is a ~36 kDa protein. G protein-coupled receptor that binds melanocyte-stimulating hormones (alpha- and beta-MSH) and corticotropin/ACTH, which are peptide products of the POMC precursor. Functions as a central component of the leptin-melanocortin pathway, which is essential for maintaining energy homeostasis. Upon activation, couples to G(s) protein, stimulating adenylate cyclase and the cAMP-dependent signaling pathway, which promotes anorexogenic signaling in the hypothalamus and contributes to a negative energy balance. Regulates food intake: activation by agonists suppresses appetite, whereas the antagonist Agouti-related protein/AGRP precludes agonist-induced signaling, thereby stimulating appetite. Modulates the firing activity of neurons in paraventricular nucleus (PVN) of the hypothalamus via alpha-MSH and AGRP regulation of inwardly rectifying potassium channel KCNJ13 closure, independently of G(s) signaling. 1. Farooqi, IS. et al. (2003) The New England journal of medicine 348, 1085-95. PMID: 126466652. Valli-Jaakola, K. et al. (2004) The Journal of clinical endocrinology and metabolism 89, 940-5. PMID: 147648183. Delhanty, PJ. et al. (2014) Molecular biology reports 41, 7967-72. PMID: 251636324. Yu, J. et al. (2020) Science (New York, N.Y.) 368, 428-433. PMID: 323275985. Israeli, H. et al. (2021) Science (New York, N.Y.) 372, 808-814. PMID: 338589926. Gantz, I. et al. (1993) The Journal of biological chemistry 268, 15174-9. PMID: 83920677. Yeo, GS. et al. (2003) Human molecular genetics 12, 561-74. PMID: 125888038. Ollmann, MM. et al. (1997) Science (New York, N.Y.) 278, 135-8. PMID: 9311920 |
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