P38 MAPK signal transduction in melanogenesis

Model of contribution of p38 MAPK signal transduction in melanogenesis. The activation of p38 by UV irradiation could directly stimulate melanogenesis increasing Usf-1-dependent transcription of tyrosinase gene (). Elevation of cAMP content leads to PKA activation and stimulation of Mitf transcription resulting in stimulation of tyrosinase, TRP-1, and DCT gene expression. Stimulation of MC1R activates ERK1/2 cascade promoting Mitf transcriptional activity and its degradation at the same time. Stimulation of MC1R by α-MSH also phosphorylates p38 MAPK. We propose that similar to ERK1/2, p38 activation could repress melanin synthesis, preventing excessive production of melanin synthesis through the accelerate degradation of melanogenic enzymes (dotted lines/arrows). p38, as well as ERK1/2, might represent a feedback system that controls tyrosinase family protein turnover, balancing the strong induction via the cAMP/PKA pathway.

Publication

p38 Regulates Pigmentation via Proteasomal Degradation of Tyrosinase. (2010) Barbara Bellei, et al. J Biol Chem. 2010 Mar 5;285(10):7288-7299. Figure: F9. All organisms Homo sapiens Mus musculus Danio rerio

Disease mentions