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Melanocortin‐1 receptor‐mediated signalling pathways activated by NDP‐MSH and HBD3 ligands
Author(s) -
Beaumont Kimberley A.,
Smit Darren J.,
Liu Yan Yan,
Chai Eric,
Patel Mira P.,
Millhauser Glenn L.,
Smith Jennifer J.,
Alewood Paul F.,
Sturm Richard A.
Publication year - 2012
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/j.1755-148x.2012.00990.x
Subject(s) - melanocortin 1 receptor , melanocortin , receptor , signalling , microbiology and biotechnology , g protein coupled receptor , chemistry , signal transduction , biology , biochemistry , gene , phenotype
Summary Binding of melanocortin peptide agonists to the melanocortin‐1 receptor of melanocytes results in eumelanin production, whereas binding of the agouti signalling protein inverse agonist results in pheomelanin synthesis. Recently, a novel melanocortin‐1 receptor ligand was reported. A β‐defensin gene mutation was found to be responsible for black coat colour in domestic dogs. Notably, the human equivalent, β‐defensin 3, was found to bind with high affinity to the melanocortin‐1 receptor; however, the action of β‐defensin as an agonist or antagonist was unknown. Here, we use in vitro assays to show that β‐defensin 3 is able to act as a weak partial agonist for cAMP signalling in human embryonic kidney (HEK) cells expressing human melanocortin‐1 receptor. β‐defensin 3 is also able to activate MAPK signalling in HEK cells stably expressing either wild type or variant melanocortin‐1 receptors. We suggest that β‐defensin 3 may be a novel melanocortin‐1 receptor agonist involved in regulating melanocyte responses in humans.