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.
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Liang et al. described marked reduction in MC2R activation with some of these peptides.
“In this work, they described the marked reduction in MC2R activation observed with some of these peptides”
From ACTH Antagonists (2016) · cites this paper as [56]
Liang et al. described peptide analogs of ACTH based on alanine and histidine substitutions around the HFRW region and in the spacing between this and the tetrabasic region.
“Liang et al. has described a number of peptide analogs of ACTH based on alanine and histidine substitutions around the HFRW region and in the spacing between this and the tetrabasic region (56).”
From ACTH Antagonists (2016) · cites this paper as [56]
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- Authors
- Liang, L., Angleson, J. K., & Dores, R. M.
- Affiliations
- University of Denver (US)
- Corresponding author
- Dores, Robert M.
- Venue
- General and Comparative Endocrinology
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 181
- Pages
- 203-210
- ISSN
- 0016-6480 (ISSN-L)
- OpenAlex
- W2104871657
- Cited by
- 35
- References
- 41
- Citations by year
- 2024: 2 · 2023: 2 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 2 · 2014: 9 · 2013: 5
- FWCI
- 0.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- General and Comparative Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (IOB 0516958)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- melanocortin 2 receptor, ACTH1-24, hormone-receptor interaction, receptor activation, melanocortin peptides, melanocortin receptors, familial glucocorticoid deficiency, structure-function relationship
- MeSH terms
- Adrenocorticotropic Hormone, Animals, Humans, Receptor, Melanocortin, Type 2
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