A single UVB exposure increases the expression of functional KIT in human melanocytes by up-regulating MITF expression through the phosphorylation of p38/CREB.
KIT is an essential receptor that modulates melanocyte function and whose function is disrupted in several pigmentary disorders. However, little is known about the effects of a single UVB exposure on the expression of KIT and two important regulatory transcription factors, MITF and AP-2 alpha, in human melanocytes. We found that a single UVB exposure of human melanocytes induces an early decrease and a subsequent increase in functional KIT expression in concert with up-regulated MITF expression. The increased MITF expression was accompanied by a markedly stimulated and prolonged phosphorylation of p38/CREB. The UVB-stimulated expression of KIT could be completely abolished by a p38 inhibitor, concomitant with a reduced phosphorylation of CREB and a down-regulation of MITF expression. Interestingly, in non-UVB exposed human melanocytes, a MEK inhibitor stimulated the phosphorylation of p38/CREB which was associated with an increased production of MITF and KIT in a pattern similar to that induced by UVB. These findings indicate that UVB stimulates functional KIT expression in human melanocytes via the up-regulation of MITF which is, in turn, due to the activation of p38 and CREB.
Mizutani
Yuki
Y
Department of Dermatology, Tokyo Women's Medical University, 8-1 Kawadacho, Shinjyuku, Tokyo, 162-8666, Japan.
Hayashi
Nobukazu
N
Kawashima
Makoto
M
Imokawa
Genji
G
D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D020930:MAP Kinase Kinase Kinases; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D051739:Microphthalmia-Associated Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000528:radiation effects; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000528:radiation effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D051739:Microphthalmia-Associated Transcription Factor; D019009:Proto-Oncogene Proteins c-kit; D048051:p38 Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases