期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 285, 期 39, 页码 29857-29862出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M110.147025
关键词
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资金
- Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan
- (University of Tokyo) from the Japan Society for Promotion of Sciences
- Center for NanoBio Integration at the University of Tokyo
- Ministry of Health, Labor, and Welfare
- MEXT of Japan
- Uehara Memorial Foundation
- Cell Science Research Foundation
- Grants-in-Aid for Scientific Research [19002011] Funding Source: KAKEN
Platelet-activating factor (PAF) is a potent proinflammatory phospholipid mediator that elicits various cellular functions under physiological and pathological conditions. We have recently identified two enzymes involved in PAF production: lysophosphatidylcholine acyltransferase-1 (LPCAT1) and LPCAT2. We found that LPCAT2 is highly expressed in inflammatory cells and is activated by lipopolysaccharide (LPS) treatment through Toll-like receptor 4. However, the molecular mechanism for the activation remains elusive. In this study, Phos-tag SDS-PAGE revealed the LPS-induced phosphorylation of LPCAT2. Furthermore, mass spectrometry and mutagenesis analyses identified Ser(34) of LPCAT2 as the phosphorylation site to enhance the catalytic activities. The experiments using inhibitors and siRNA against MAPK cascades demonstrated that LPCAT2 phosphorylation through LPS-TLR4 signaling may directly depend on MAPK-activated protein kinase 2 (MAPKAP kinase 2 or MK2). These findings develop a further understanding of both PAF production and phospholipid remodeling triggered by inflammatory stimuli. Specific inhibition of the PAF biosynthetic activity by phosphorylated LPCAT2 will provide a novel target for the regulation of inflammatory disorders.
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