Molecular cloning, expression, and gene localization of a fourth melanocortin receptor

Pituitary neuropeptides and B lymphocyte function

“…82 At the time of identification of these two receptors, studies of genomic DNA suggested the presence of several other related genes in humans. These were identified in fairly rapid succession as: MC3R, 83,84 a receptor expressed in brain and placenta which exhibited equivalent responses to ACTH, α-MSH, β-MSH and γ-MSH; MC4R, 85 a second brain MCR with relative specificity for α-MSH and ACTH; and MC5R, [86][87][88][89] a widely expressed receptor (in skin, muscle, thymus, spleen, adrenal, bone marrow and cerebellum) with ligand binding characteristics similar to those of MC1R. Recent studies of cAMP responses in cell lines overexpressing the five different MCRs have shown evidence of a distinct profile of MCR engagement by RCI compared to synthetic ACTH analogues.…”

“…To complement these observations on MCR expression, we recently queried the RNA-Seq data sets from previously published studies 5,6 for additional information on MCR mRNA expression in human B cells. 35 MC1R mRNA was the most abundant melanocortin receptor transcript expressed T A B L E 3 The melanocortin receptors and their ligand specificities [80][81][82][83][84][85][86][87][88][89] 4A). The MCRassociated proteins MRAP1 and MRAP2 were either undetectable or expressed at levels below threshold for valid statistical comparisons in samples from cells cultured under either basal or stimulated conditions.…”

Melanocortin-4 Receptor Polymorphisms in Turkish Pediatric Obese Patients

“…12 In 1998, 2 groups first reported heterozygous MC4R frameshift mutations associated with autosomal dominant earlyonset severe obesity. 13 Since then, several mutations have been reported in various study populations with severe obesity. 6 To date, more than 50 mutations have been reported.…”

“…A signal for the surface expression of the receptor is present in the C-terminal tail of the receptor, and other substitution mutations occurring throughout the receptor also result in impaired cell surface expression and could potentially affect receptor folding. 6,13,14 The most common MC4R missense variant is the Val103Ileu polymorphism (rs2229616), which is related to obesity. However, limited studies have evaluated the effect of the Val103Ile polymorphism of the MC4R gene on energy expenditure.…”

Pharmacological modulation of dual melanocortin‐4 receptor signaling by melanocortin receptor accessory proteins in the Xenopus laevis

“…Melanocyte stimulating hormone (α‐MSH) and agouti‐related protein (AgRP) are two classic endogenous regulators of MC4R in the arcuate nucleus neurons (Cone, 2005; Flier, 2004). α‐MSH activates its signaling to inhibit appetite and improve energy expenditure while AgRP antagonizes MC4R signaling by competitive binding with α‐MSH (Gantz et al, 1993; Ollmann et al, 1997; Shutter et al, 1997). Recently, osteoblast‐secreted lipocalin 2 (LCN2) was identified as a new endogenous agonist with the capability to cross the blood–brain barrier and suppress appetite through hypothalamic MC4R signaling (Mosialou et al, 2017).…”