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FEBS Lett. 2009 Oct 6;583(19):3269-74. Epub 2009 Sep 13.
Melanocortin 1 receptor mutations impact differentially on signalling to
the cAMP and the ERK mitogen-activated protein kinase pathways.
Herraiz C, Jimenez-Cervantes C, Zanna P, Garcia-Borron JC.
Department of Biochemistry and Molecular Biology, School of Medicine,
University of Murcia, 30100 Espinardo, Spain.
Melanocortin 1 receptor (MC1R), a Gs protein-coupled receptor expressed
in melanocytes, is a major determinant of skin pigmentation, phototype
and cancer risk. MC1R activates cAMP and mitogen-activated protein
kinase ERK1/ERK2 signalling. When expressed in rat pheochromocytoma cell
line cells, the R151C, R160W and D294H MC1R variants associated with
melanoma and impaired cAMP signalling mediated ERK activation and
ERK-dependent, agonist-induced neurite outgrowth comparable with
wild-type. Dose-response curves for ERK activation and cAMP production
indicated higher sensitivity of the ERK response. Thus, the
melanoma-associated MC1R mutations impact differently on cAMP and ERK
signalling, suggesting that cAMP is not responsible for functional
coupling of MC1R to the ERK cascade.
Publication Types:
* Research Support, Non-U.S. Gov't
PMID: 19755124 |
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