Signaling Cascades Activated by UVB in Human Melanocytes Lead to the Increased Expression of Melanocyte-receptors, Endothelin B Receptor and c-KIT¶

Abstract

A single exposure of normal human melanocytes (NHMs) to ultraviolet B (UVB) radiation induces a distinct increase in the expression of c-KIT and endothelin B receptor (EDNRB) and up-regulates the expression of microphthalmia-associated transcription factor (MITF). In this review, we clarify the signaling mechanisms by which UVB stimulates the expression of MITF in NHMs, thus leading to up-regulation of those two important melanogenic receptors. The increased expression of MITF in UVB-exposed NHMs is accompanied by a markedly stimulated and prolonged phosphorylation of p38/CREB. The UVB-stimulated expression of c-KIT and EDNRB could be completely abolished by a p38 inhibitor concomitant with a reduced phosphorylation of CREB and a down-regulation of MITF expression. The UVB exposure of NHMs stimulates the phosphorylation of p38 and c-jun N-terminal kinase, but not ERK, followed by the increased phosphorylation of MSK1 and subsequently CREB. Post-irradiation treatment with the MSK1 inhibitor H89 significantly down-regulates the increased mRNA and protein expression of MITF, EDNRB and c-KIT in UVB-exposed NHMs. Our findings indicate for the first time that the increased expression of MITF that leads to the up-regulation of melanocyte-specific proteins in UVB-exposed NHMs is mediated via activation of the p38/MSK1/CREB axis but not the ERK/RSK/CREB axis.

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