ArticleInternational journal of biological sciences2015
Biased signaling in naturally occurring mutations in human melanocortin-3 receptor gene.
Article in International journal of biological sciences, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 34 citations in OpenAlex.
- Neural Melanocortin Receptors in Fish: Insights into Growth Regulation and Aquaculture Advancement.Biomolecules · 2026Review
- Melanocortin 3 Receptors Do Not Specifically Localize to Primary Cilia in Cultured Human and Rodent Neurons.Cell biochemistry and function · 2026Article
- Cross-species studies implicate the melanocortin 3 receptor more strongly in the control of pubertal development than energy balance.Molecular metabolism · 2026Article
- Molecular cloning and functional characterization of melanocortin-3 receptor in grass carp (Ctenopharyngodon idella).Fish physiology and biochemistry · 2023Article
- Melanocortin-5 Receptor: Pharmacology and Its Regulation of Energy Metabolism.International journal of molecular sciences · 2022Review
- Structural Elements Directing G Proteins and β-Arrestin Interactions with the Human Melatonin Type 2 Receptor Revealed by Natural Variants.ACS pharmacology & translational science · 2022Article
- Biased signaling in naturally occurring mutations of G protein-coupled receptors associated with diverse human diseases.Biochimica et biophysica acta. Molecular basis of disease · 2021Review
- Melanocortin Regulation of Inflammation.Frontiers in endocrinology · 2019Review
- Biased signaling at neural melanocortin receptors in regulation of energy homeostasis.Biochimica et biophysica acta. Molecular basis of disease · 2017Review
- Polymorphisms and mutations in the melanocortin-3 receptor and their relation to human obesity.Biochimica et biophysica acta. Molecular basis of disease · 2017Review
- Functions of DPLIY motif and helix 8 of human melanocortin-3 receptor.Journal of molecular endocrinology · 2015Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The melanocortin-3 receptor (MC3R) is primarily expressed in the hypothalamus and plays an important role in the regulation of energy homeostasis. Recently, some studies demonstrated that MC3R also signals through mitogen-activated protein kinases (MAPKs), especially extracellular signal-regulated kinases 1 and 2 (ERK1/2). ERK1/2 signaling is known to alter gene expression, potentially contributing to the prolonged action of melanocortins on energy homeostasis regulation. In the present study, we performed detailed functional studies on 8 novel naturally occurring MC3R mutations recently reported, and the effects of endogenous MC3R agonist, α-melanocyte stimulating hormone (MSH), on ERK1/2 signaling on all 22 naturally occurring MC3R mutations reported to date. We found that mutants D158Y and L299V were potential pathogenic causes to obesity. Four residues, F82, D158, L249 and L299, played critical roles in different aspects of MC3R function. α-MSH exhibited balanced activity in Gs-cAMP and ERK1/2 signaling pathways in 15 of the 22 mutant MC3Rs. The other 7 mutant MC3Rs were biased to either one of the signaling pathways. In summary, we provided novel data about the structure-function relationship of MC3R, identifying residues important for receptor function. We also demonstrated that some mutations exhibited biased signaling, preferentially activating one intracellular signaling pathway, adding a new layer of complexity to MC3R pharmacology.
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