title: Characterization of the bioactive motif of neuregulin-1, a fibroblast-derived paracrine factor that regulates the constitutive color and the function of melanocytes in human skin.
abstract: Interactions between melanocytes and neighboring cells in the skin (keratinocytes and fibroblasts) play important roles in regulating human skin color. We recently reported that neuregulin-1 (NRG1) is highly expressed in fibroblasts from Fitzpatrick type VI skin (the darkest) and at least in part determines the constitutive color of human skin. We have now characterized the bioactive motif of NRG1 that is involved in modulating melanin production in human melanocytes. We found that 8-mer motifs (PSRYLCKC and LCKCPNEF) increased melanin production but did not increase the proliferation of melanocytes; the minimum fragment that could elicit that effect was the tetrapeptide LCKC. This smaller bioactive peptide might have an advantage in clinical applications in which it modulates only pigmentation and does not stimulate melanocyte proliferation.
authors.affiliation: Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Wonseon
authors.initials: W
authors.lastname: Choi
authors.forename: Ludger
authors.initials: L
authors.lastname: Kolbe
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Hearing
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D020890:Neuregulin-1 / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D019899:Paracrine Communication / Q000187:drug effects; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010858:Pigmentation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012867:Skin / Q000166:cytology*
chemical_list: D020890:Neuregulin-1; D010455:Peptides; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases