Cited by 189melanin and skin pigmentationMelanoma and MAPK PathwaysReceptor Mechanisms and Signaling

MC 1R, the c AMP pathway, and the response to solar UV: extending the horizon beyond pigmentation

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García‐Borrón, Jose C., Abdel‐Malek, Zalfa, Jiménez‐Cervantes, Celia·2014·Pigment Cell & Melanoma Research

Abstract

Summary: The melanocortin 1 receptor (MC 1R) is a G protein‐coupled receptor crucial for the regulation of melanocyte proliferation and function. Upon binding melanocortins, MC 1R activates several signaling cascades, notably the c AMP pathway leading to synthesis of photoprotective eumelanin. Polymorphisms in the MC 1R 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 MC 1R 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 MC 1R structural and functional properties, as well as on its intracellular trafficking and signaling. We also review the current knowledge about the function of MC 1R as a skin cancer, particularly melanoma, susceptibility gene and how it modulates the response of melanocytes to UVR.

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  • In wild-type eumelanic subjects, α-MSH-mediated stimulation of MC1R results in activation of the associated Gs protein, which activates adenyl cyclase and increases cAMP, responsible for effects such as activation of tyrosinase, Tyrp1 and Dct to produce eumelanins.

    “In wild-type eumelanic subjects, α-MSH-mediated stimulation of MC1R results in activation of the associated Gs protein, which activates adenyl cyclase and increases the levels of cellular cyclic adenosine 3’,5’-monophosphate (cAMP), which is responsible for many of the effects of α-MSH, such as activation of tyrosinase (the rate-limiting enzyme in melanogenesis), tyrosinase-related protein 1 (Tyrp”

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Authors
García‐Borrón, J. C., Abdel‐Malek, Z., & Jiménez‐Cervantes, C.
Affiliations
  • Department of Biochemistry and Molecular Biology School of Medicine University of Murcia Murcia Spain
  • University of Cincinnati (US)
  • Instituto Murciano de Investigación Biosanitaria (ES)
Venue
Pigment Cell & Melanoma Research
Publisher
Wiley
Published
2014-05-30
Volume
27
Issue
5
Pages
699-720
ISSN
  • 1755-1471 (ISSN-L)
  • 1755-148X
OpenAlex
W2036734230
Cited by
187
References
256
Citations by year
2026: 12 · 2025: 11 · 2024: 16 · 2023: 14 · 2022: 13 · 2021: 16 · 2020: 24 · 2019: 14 · 2018: 18 · 2017: 16 · 2016: 19 · 2015: 11 · 2014: 2
FWCI
1.60
Type
journal article
Language
en
Open access
Locations
  • Pigment Cell & Melanoma Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
MINECO, Spain (SAF2012-32134)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
MC1R, cAMP signaling, melanocyte proliferation, skin pigmentation, hair color, melanoma susceptibility, skin cancer predisposition, receptor trafficking, G protein-coupled receptor signaling
MeSH terms
Cyclic AMP, Alleles, Animals, DNA Damage, Humans, Ligands, Melanocytes, Melanoma, Mutation, Neoplasms, Radiation-Induced, Phenotype, Pigmentation, Polymorphism, Genetic, Protein Processing, Post-Translational, Skin Neoplasms, Skin Pigmentation, Ultraviolet Rays, Genetic Variation, Signal Transduction, Protein Structure, Tertiary, Genetic Predisposition to Disease, Gene Expression Profiling, Protein Transport, Receptor, Melanocortin, Type 1, Mice

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