Park, Hee-YoungWu, ChristinaYaar, MinaStachur, Christina M.Kosmadaki, MaritaGilchrest, Barbara A.2012-01-122012-01-1220092009-12-30Park, Hee-Young, Christina Wu, Mina Yaar, Christina M. Stachur, Marita Kosmadaki, Barbara A. Gilchrest. "Role of BMP-4 and Its Signaling Pathways in Cultured Human Melanocytes" International Journal of Cell Biology 2009:750482.1687-8884https://hdl.handle.net/2144/3403Bone Morphogenetic Protein (BMP-4) was shown to down-regulate melanogenesis, in part, by decreasing the level of tyrosinase [Yaar et al. (2006) JBC:281]. Results presented here show that BMP-4 down-regulated the protein levels of TRP-1, PKC-β, and MCI-R. When paired cultures of human melanocytes were treated with vehicle or BMP-4 (25ng/ml), MAPK/ERK were phosphorylated within one hour of BMP-4 treatment. Then the activated MAPK/ERK caused an acute phosphorylation of MITF, followed by proteosome-mediated degradation of MITF, the key transcription factor for melanogenic proteins [Wu et al. (2000) Gene & Development:14]. However, prolonged exposure of melanocytes to BMP-4 (up to 48 hours) caused a decrease in the level of MITF-M transcript. In addition, BMP-4 decreased the intracellular level of cAMP, the key regulator of MITF expression. These results demonstrate that BMP-4 activates MAPK/ERK signaling pathway to transiently activate MITF; however, chronic treatment of BMP-4 to melanocytes causes a down-regulation of the expression of MITF, possibly in a cAMP-dependent pathway.enCopyright 2009 Hee-Young Park et al.Article10.1155/2009/750482201308212814237