title: Melanocortin-1 receptor-mediated signalling pathways activated by NDP-MSH and HBD3 ligands.
abstract: 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.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Qld, Australia.
authors.forename: Kimberley A
authors.initials: KA
authors.lastname: Beaumont
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Smit
authors.forename: Yan Yan
authors.initials: YY
authors.lastname: Liu
authors.forename: Eric
authors.initials: E
authors.lastname: Chai
authors.forename: Mira P
authors.initials: MP
authors.lastname: Patel
authors.forename: Glenn L
authors.initials: GL
authors.lastname: Millhauser
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Smith
authors.forename: Paul F
authors.initials: PF
authors.lastname: Alewood
authors.forename: Richard A
authors.initials: RA
authors.lastname: Sturm
mesh_terms: D054366:Agouti Signaling Protein / Q000494:pharmacology; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D044102:Receptor, Melanocortin, Type 1 / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000494:pharmacology; D023083:beta-Defensins / Q000819:agonists / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D054366:Agouti Signaling Protein; D016588:Anticarcinogenic Agents; C422950:DEFB103A protein, human; D008024:Ligands; D044102:Receptor, Melanocortin, Type 1; D023083:beta-Defensins; D000521:alpha-MSH; C027756:MSH, 4-Nle-7-Phe-alpha-; D000242:Cyclic AMP