Document Detail

Melanocortin 1 receptor mutations impact differentially on signalling to the cAMP and the ERK mitogen-activated protein kinase pathways.
MedLine Citation:
PMID:  19755124     Owner:  NLM     Status:  MEDLINE    
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.
Cecilia Herraiz; Celia Jiménez-Cervantes; Paola Zanna; José C García-Borrón
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-09-13
Journal Detail:
Title:  FEBS letters     Volume:  583     ISSN:  1873-3468     ISO Abbreviation:  FEBS Lett.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-10-05     Completed Date:  2009-11-13     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0155157     Medline TA:  FEBS Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  3269-74     Citation Subset:  IM    
Department of Biochemistry and Molecular Biology, School of Medicine, University of Murcia, 30100 Espinardo, Spain.
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MeSH Terms
Cell Line, Tumor
Cyclic AMP / metabolism*
Enzyme Activation
Extracellular Signal-Regulated MAP Kinases / metabolism*
Melanoma / genetics*
Receptor, Melanocortin, Type 1 / genetics,  metabolism*
Signal Transduction / genetics
Reg. No./Substance:
0/Receptor, Melanocortin, Type 1; 60-92-4/Cyclic AMP; EC Signal-Regulated MAP Kinases

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