MC1R, the cAMP pathway, and the response to solar UV: extending the horizon beyond pigmentation
- PMID: 24807163
- PMCID: PMC4150834
- DOI: 10.1111/pcmr.12257
MC1R, the cAMP pathway, and the response to solar UV: extending the horizon beyond pigmentation
Abstract
The melanocortin 1 receptor (MC1R) is a G protein-coupled receptor crucial for the regulation of melanocyte proliferation and function. Upon binding melanocortins, MC1R activates several signaling cascades, notably the cAMP pathway leading to synthesis of photoprotective eumelanin. Polymorphisms in the MC1R gene are a major source of normal variation of human hair color and skin pigmentation, response to ultraviolet radiation (UVR), and skin cancer susceptibility. The identification of a surprisingly high number of MC1R natural variants strongly associated with pigmentary phenotypes and increased skin cancer risk has prompted research on the functional properties of the wild-type receptor and frequent mutant alleles. We summarize current knowledge on MC1R structural and functional properties, as well as on its intracellular trafficking and signaling. We also review the current knowledge about the function of MC1R as a skin cancer, particularly melanoma, susceptibility gene and how it modulates the response of melanocytes to UVR.
Keywords: MC1R variants; Melanocortin 1 receptor; cAMP; melanocytes; melanoma; ultraviolet radiation.
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Figures



References
-
- Abdel-Malek ZA, Kadekaro AL, Kavanagh RJ, et al. Melanoma prevention strategy based on using tetrapeptide alpha-MSH analogs that protect human melanocytes from UV-induced DNA damage and cytotoxicity. FASEB J. 2006;20:1561–1563. - PubMed
-
- Abdel-Malek ZA, Ruwe A, Kavanagh-Starner R, Kadekaro AL, Swope V, Haskell-Luevano C, Koikov L, Knittel JJ. alpha-MSH tripeptide analogs activate the melanocortin 1 receptor and reduce UV-induced DNA damage in human melanocytes. Pigment Cell Melanoma Res. 2009;22:635–644. - PubMed
-
- Aberdam E, Bertolotto C, Sviderskaya EV, de TV, Hemesath TJ, Fisher DE, Bennett DC, Ortonne JP, Ballotti R. Involvement of microphthalmia in the inhibition of melanocyte lineage differentiation and of melanogenesis by agouti signal protein. J. Biol. Chem. 1998;273:19560–19565. - PubMed
-
- Abrisqueta M, Herraiz C, Perez Oliva AB, Sanchez-Laorden BL, Olivares C, Jimenez-Cervantes C, Garcia-Borron JC. Differential and competitive regulation of human melanocortin 1 receptor signaling by beta-arrestin isoforms. J. Cell Sci. 2013;126:3724–3737. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources