title: PP2A and DUSP6 are involved in sphingosylphosphorylcholine-induced hypopigmentation.
abstract: Activation of extracellular signal-related kinase (ERK) is involved in decreased melanogenesis by sphingosylphosphorylcholine (SPC). In the present study, we confirmed that SPC activated ERK and that a specific inhibitor of the ERK pathway (PD98059) recovered SPC-induced hypopigmentation. Moreover, we found that SPC significantly reduces protein phosphatase 2A (PP2A) activity in Mel-Ab cells, and that PP2A activator treatment abrogated SPC-induced hypopigmentation. We determined that α-melanocyte-stimulating hormone (α-MSH) increased the expression of dual-specificity phosphatase 6 (DUSP6), an ERK phosphatase, in a time-dependent manner. In contrast, SPC decreased the level of DUSP6 in Mel-Ab cells. Furthermore, inhibiting DUSP6 increased ERK activation and subsequently augmented the SPC-induced hypopigmenting effects. Taken together, our data suggest that SPC-induced phosphatase inhibition is also responsible for the hypopigmentary effects.
authors.affiliation: Department of Biochemistry, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyo-Soon
authors.initials: HS
authors.lastname: Jeong
authors.forename: Kyoung-Chan
authors.initials: KC
authors.lastname: Park
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Kim
mesh_terms: D000818:Animals; D002460:Cell Line; D054642:Dual Specificity Phosphatase 6 / Q000378:metabolism*; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D017496:Hypopigmentation / Q000139:chemically induced / Q000201:enzymology*; D020935:MAP Kinase Signaling System; D008543:Melanins / Q000096:biosynthesis; D051379:Mice; D010766:Phosphorylation; D010767:Phosphorylcholine / Q000031:analogs & derivatives; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D013110:Sphingosine / Q000031:analogs & derivatives
chemical_list: D020536:Enzyme Activators; D005419:Flavonoids; D008543:Melanins; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D048049:Extracellular Signal-Regulated MAP Kinases; D054648:Protein Phosphatase 2; D054642:Dual Specificity Phosphatase 6; C517036:Dusp6 protein, mouse; D013110:Sphingosine; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one