title: Using the human melanocortin-2 receptor as a model for analyzing hormone/receptor interactions between a mammalian MC2 receptor and ACTH(1-24).
abstract: When considering the interactions between the melanocortin peptides (i.e., ACTH, α-MSH, β-MSH, γ-MSH) and the melanocortin receptors (i.e., MC1R, MC2R, MC3R, MC4R, MC5R), it appears that the structure/function relationship between ACTH and MC2R is the most complicated. Human ACTH(1-24) and the human melanocortin-2 receptor provide a useful model system for understanding how ACTH emerged as the sole ligand for the melanocortin-2 receptor of bony vertebrates. This review will discuss how studies utilizing analogs of hACTH(1-24) have revealed two critical amino acid motifs in this ligand (HFRW and KKRRP) which are required for activation of the melanocortin-2 receptor. In addition, observations on the unique activation features of the melanocortin-2 receptor, as revealed from studies on Familial Glucocorticoid Deficiency, will be considered. Finally, the evolutionary implications of the relationship between MC2R and MRAP1 will be discussed.
authors.affiliation: University of Denver, Department of Biological Sciences, Denver, CO 80210, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Liang
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Angleson
authors.forename: Robert M
authors.initials: RM
authors.lastname: Dores
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives / Q000378:metabolism*; D000818:Animals; D006801:Humans; D044103:Receptor, Melanocortin, Type 2 / Q000378:metabolism*
chemical_list: D044103:Receptor, Melanocortin, Type 2; D000324:Adrenocorticotropic Hormone