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Title: | Agouti protein, mahogunin, and attractin in pheomelanogenesis and melanoblast-like alteration of melanocytes: a cAMP-independent pathway |
Authors: | Hida, Tokimasa; Wakamatsu, Kazumasa; Sviderskaya, Elena V.; Donkin, Andrew J.; Montoliu, Lluís ; Lamoreux, M. Lynn; Yu, Bin; Millhauser, Glenn L.; Ito, Shosuke; Barsh, Gregory S.; Jimbow, Kowichi; Bennett, Dorothy C. |
Keywords: | Pheomelanin Mc1r Melanoblast Attractin Mahogunin Agouti |
Issue Date: | 15-May-2009 |
Publisher: | John Wiley & Sons |
Citation: | Pigment Cell and Melanoma Research 22(5): 623–634 (2009) |
Abstract: | Melanocortin-1 receptor (MC1R) and its ligands, a-melanocyte stimulating hormone (aMSH) and agouti signaling protein (ASIP), regulate switching between eumelanin and pheomelanin synthesis in melanocytes. Here we
investigated biological effects and signaling pathways of ASIP. Melan-a non agouti (a ⁄ a) mouse melanocytes produce
mainly eumelanin, but ASIP combined with phenylthiourea and extra cysteine could induce over 200-fold increases in the pheomelanin to eumelanin ratio, and a tan-yellow color in pelletted cells. Moreover, ASIP-treated cells showed reduced proliferation and a melanoblast-like appearance, seen also in melanocyte lines from yellow (Ay ⁄ a and Mc1re ⁄ Mc1re) mice. However ASIP-YY, a C-terminal fragment of ASIP, induced neither biological nor pigmentary changes. As, like ASIP, ASIP-YY inhibited the cAMP rise induced by aMSH analog NDP-MSH, and reduced cAMP level without added MSH, the morphological changes and depigmentation seemed independent of cAMP signaling. Melanocytes genetically null for ASIP mediators attractin or mahogunin (Atrnmg-3J ⁄ mg-3J or Mgrn1md-nc ⁄ md-nc) also responded to both ASIP and ASIP-YY in cAMP level, while only ASIP altered their proliferation and (in part) shape. Thus, ASIP–MC1R signaling includes a cAMP-independent pathway through attractin and mahogunin, while the known cAMP-dependent component requires neither attractin nor mahogunin. |
Publisher version (URL): | http://dx.doi.org/10.1111/j.1755-148X.2009.00582.x |
URI: | http://hdl.handle.net/10261/40198 |
DOI: | http://dx.doi.org/10.1111/j.1755-148X.2009.00582.x |
ISSN: | 1755-1471 |
E-ISSN: | 1755-148X |
Appears in Collections: | (CNB) Artículos |
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