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: Hyo-Soon Jeong, Kyoung-Chan Park, Dong-Seok Kim
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 367 Issue 1-2 Pg. 43-9 (Aug 2012) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 22544520 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Activators
• Flavonoids
• Melanins
• sphingosine phosphorylcholine
• Phosphorylcholine
• Extracellular Signal-Regulated MAP Kinases
• Protein Phosphatase 2
• Dual Specificity Phosphatase 6
• Dusp6 protein, mouse
• Sphingosine
• 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Topics

• Animals
• Cell Line
• Dual Specificity Phosphatase 6 (metabolism)
• Enzyme Activation
• Enzyme Activators (pharmacology)
• Extracellular Signal-Regulated MAP Kinases (antagonists & inhibitors, metabolism)
• Flavonoids (pharmacology)
• Hypopigmentation (chemically induced, enzymology)
• MAP Kinase Signaling System
• Melanins (biosynthesis)
• Mice
• Phosphorylation
• Phosphorylcholine (analogs & derivatives)
• Protein Phosphatase 2 (metabolism)
• Protein Processing, Post-Translational
• Sphingosine (analogs & derivatives)