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Melanocortin 1 receptor mutations impact differentially on signalling to the cAMP and the ERK mitogen‐activated protein kinase pathways
Author(s) -
Herraiz Cecilia,
Jiménez-Cervantes Celia,
Zanna Paola,
García-Borrón José C.
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.09.023
Subject(s) - melanocortin 1 receptor , mapk/erk pathway , protein kinase a , receptor , mitogen activated protein kinase , biology , kinase , endocrinology , medicine , microbiology and biotechnology , cancer research , biochemistry , gene , allele
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.