The Cloning of a Family of Genes That Encode the Melanocortin Receptors

Abstract

Melanocyte-stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH) regulate pigmentation and adrenal cortical function, respectively. These peptides also have a variety of biological activities in other areas, including the brain, the pituitary, and the immune system. A complete understanding of the biological activities of these hormones requires the isolation and characterization of their corresponding receptors. The murine and human MSH receptors (MSH-Rs) and a human ACTH receptor (ACTH-R) were cloned. These receptors define a subfamily of receptors coupled to guanine nucleotide-binding proteins that may include the cannabinoid receptor.

Anti-inflammatory and anti-invasive effects of α-melanocyte-stimulating hormone in human melanoma cells

“…No immunoreactivity was observed for cells incubated with isotype control serum. Western immunoblotting using the same primary anti-MC-1R antibody revealed a reactive band at 35 kDa molecular mass for the HBL, A375-SM and C8161 melanoma cell lines ( Figure 1B); close to the predicted size of MC-1R, based on sequencing information (Mountjoy et al, 1992). The extracts of HEK293 cells did not reveal a similar band.…”

“…Five receptors (MC-1R -MC-5R) have been cloned to date (Mountjoy et al, 1992) and MC-1R is expressed on human keratinocytes, melanocytes and melanoma cells (Donatien et al, 1992;De Luca et al, 1993;Bohm et al, 1999). Loss-of-function polymorphic variants exist (Valverde et al, 1995) and are associated with red-haired individuals who pigment poorly (Schiöth et al, 1999).…”

Two cysteine substitutions in the MC1R generate the blue variant of the arctic fox (Alopex lagopus) and prevent expression of the white winter coat

“…Sequence comparison for MC1R regions that span amino acid 5 (amino acid 1-9 in the left box) and 280 (region 276-284, or 274-282 in mouse which has a two aa deletion). For the regions illustrated, additional species have been shown to be identical to species included in this figure [5,[10][11][12]16,18,25,26]. rable to the TM2/TM3 -mutations might be foreseen.…”

Structure–activity studies of new melanocortin peptides containing an aromatic amino acid at the N-terminal position

“…There are five known melanocortin receptor (MCR) subtypes, all of which belong to the family of seven transmembrane G-protein coupled receptors (GPCRs), and whose activation is linked to the generation of intracellular cAMP [3,7,8,12,[14][15][16]22,31,34,38]. Importantly, the interaction of the melanocortin peptides with their receptors can be modified by two endogenous protein antagonists, agouti, and agouti-related protein, which are the products of two distinct genes [33,35].…”