Melanocortin 1 receptor mutations impact differentially on signalling to the cAMP and the ERK mitogen-activated protein kinase pathways.
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.
Herraiz
Cecilia
C
Department of Biochemistry and Molecular Biology, School of Medicine, University of Murcia, 30100 Espinardo, Spain.
Jiménez-Cervantes
Celia
C
Zanna
Paola
P
García-Borrón
José C
JC
D000818:Animals; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000378:metabolism*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D051379:Mice; D009154:Mutation; D051381:Rats; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics
D044102:Receptor, Melanocortin, Type 1; D000242:Cyclic AMP; D048049:Extracellular Signal-Regulated MAP Kinases