Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 289, Issue 22, Pages 15566-15576Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M114.558874
Keywords
Enzyme Catalysis; Inflammation; Macrophages; Membrane Lipids; Phosphorylation; Protein Kinase C (PKC); Platelet-activating Factor; Lysophospholipid Acyltransferase
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Funding
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan
- National Center for Global Health and Medicine [24-001, 25-201]
- Takeda Science Foundation
- Cell Science Research Foundation
- CREST, the Japan Science and Technology Agency
- Gushinkai
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Platelet-activating factor (PAF), a potent proinflammatory lipid mediator, is synthesized rapidly in response to extracellular stimuli by the activation of acetyl-CoA:lyso-PAF acetyltransferase (lyso-PAFAT). We have reported previously that lyso-PAFAT activity is enhanced in three distinct ways in mouse macrophages: rapid activation (30 s) after PAF stimulation and minutes to hours after LPS stimulation. Lysophosphatidylcholine acyltransferase 2 (LPCAT2) was later identified as a Ca2+-dependent lyso-PAFAT. However, the mechanism of rapid lyso-PAFAT activation within 30 s has not been elucidated. Here we show a new signaling pathway for rapid biosynthesis of PAF that is mediated by phosphorylation of LPCAT2 at Ser-34. Stimulation by either PAF or ATP resulted in PKC-mediated phosphorylation of LPCAT2 to enhance lyso-PAFAT activity and rapid PAF production. Biochemical analyses showed that the phosphorylation of Ser-34 resulted in augmentation of V-max with minimal K-m change. Our results offer an answer for the previously unknown mechanism of rapid PAF production.
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