Rapid Production of Platelet-activating Factor Is Induced by Protein Kinase C{alpha}-mediated Phosphorylation of Lysophosphatidylcholine Acyltransferase 2 [Enzymology]

April 17th, 2014 by Morimoto, R., Shindou, H., Tarui, M., Shimizu, T.

Platelet-activating factor (PAF), a potent pro-inflammatory lipid mediator, is rapidly synthesized in response to extracellular stimuli by the activation of acetyl-CoA:lyso-PAF acetyltransferase (lyso-PAFAT). We have previously reported that lyso-PAFAT activity is enhanced in three distinct ways in mouse macrophages: (i) rapid activation (30 seconds) after PAF-stimulation and (ii, iii) minutes to hours after lipopolysaccharide (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 Ser34. Stimulation by either PAF or ATP resulted in protein kinase Cα (PKCα)-mediated phosphorylation of LPCAT2 to enhance lyso-PAFAT activity and rapid PAF production. Biochemical analyses showed that the phosphorylation of Ser34 resulted in augmentation of Vmax with minimal Km change. Our results offer an answer for the previously unknown mechanism of rapid PAF production.
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