期刊
JOURNAL OF LIPID RESEARCH
卷 53, 期 8, 页码 1513-1521出版社
ELSEVIER
DOI: 10.1194/jlr.M025395
关键词
PP2C; Ser/Thr phosphatases; sphingolipids
资金
- National Institutes of Health grant [CA 87584]
- Grants-in-Aid for Scientific Research [23790366] Funding Source: KAKEN
Ceramide is a bioactive sphingolipid with many associated biological outcomes, yet there is a significant gap in our current understanding of how ceramide mediates these processes. Previously, ceramide has been shown to activate protein phosphatase (PP) 1 and 2A. While continuing this line of work, a late fraction from a Mono-Q column was consistently observed to be activated by ceramide, yet PP1 and PP2A were undetectable in this fraction. Proteomic analysis of this fraction revealed the identity of the phosphatase to be PP2C gamma/PPM1G. This was consistent with our findings that PP2C gamma 1-eluted in a high salt fraction due to its strongly acidic domain, and 2-was insensitive to okadaic acid. Further characterization was performed with PP2C alpha, which showed robust activation by C-6-ceramide. Activation was specific for the erythro conformation of ceramide and the presence of the acyl chain and hydroxyl group at the first carbon. In order to demonstrate more physiological activation of PP2C alpha by ceramide, phospho-p38 delta was utilized as substrate. Indeed, PP2C alpha induced the dephosphorylation of p38 delta only in the presence of C-16-ceramide.(jlr) Taken together, these results show that the PP2C family of phosphatases is activated by ceramide, which may have important consequences in mediating the biological effects of ceramide.-Perry, D. M., K. Kitatani, P. Roddy, M. El-Osta, and Y. A. Hannun. Identification and characterization of protein phosphatase 2C activation by ceramide. J. Lipid Res. 2012. 53: 1513-1521.
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