Role of BMP-4 and Its Signaling Pathways in Cultured Human Melanocytes

Bone 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 wer...

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Main Authors: Hee-Young Park, Christina Wu, Mina Yaar, Christina M. Stachur, Marita Kosmadaki, Barbara A. Gilchrest
Format: Article
Language:English
Published: Wiley 2009-01-01
Series:International Journal of Cell Biology
Online Access:http://dx.doi.org/10.1155/2009/750482
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author Hee-Young Park
Christina Wu
Mina Yaar
Christina M. Stachur
Marita Kosmadaki
Barbara A. Gilchrest
author_facet Hee-Young Park
Christina Wu
Mina Yaar
Christina M. Stachur
Marita Kosmadaki
Barbara A. Gilchrest
author_sort Hee-Young Park
collection DOAJ
description Bone 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 (25 ng/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.
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spelling doaj-art-8b4f1aaf8b754c73b1ff1cdef4ea6b452025-02-03T01:27:11ZengWileyInternational Journal of Cell Biology1687-88761687-88842009-01-01200910.1155/2009/750482750482Role of BMP-4 and Its Signaling Pathways in Cultured Human MelanocytesHee-Young Park0Christina Wu1Mina Yaar2Christina M. Stachur3Marita Kosmadaki4Barbara A. Gilchrest5Department of Dermatology, School of Medicine, Boston University, Boston, MA 02118, USADepartment of Dermatology, School of Medicine, Boston University, Boston, MA 02118, USADepartment of Dermatology, School of Medicine, Boston University, Boston, MA 02118, USADepartment of Dermatology, School of Medicine, Boston University, Boston, MA 02118, USADepartment of Dermatology, School of Medicine, Boston University, Boston, MA 02118, USADepartment of Dermatology, School of Medicine, Boston University, Boston, MA 02118, USABone 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 (25 ng/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.http://dx.doi.org/10.1155/2009/750482
spellingShingle Hee-Young Park
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
title Role of BMP-4 and Its Signaling Pathways in Cultured Human Melanocytes
title_full Role of BMP-4 and Its Signaling Pathways in Cultured Human Melanocytes
title_fullStr Role of BMP-4 and Its Signaling Pathways in Cultured Human Melanocytes
title_full_unstemmed Role of BMP-4 and Its Signaling Pathways in Cultured Human Melanocytes
title_short Role of BMP-4 and Its Signaling Pathways in Cultured Human Melanocytes
title_sort role of bmp 4 and its signaling pathways in cultured human melanocytes
url http://dx.doi.org/10.1155/2009/750482
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