Rapid production of platelet-activating factor is induced by protein kinase Cα-mediated phosphorylation of lysophosphatidylcholine acyltransferase 2 protein.
J Biol Chem
; 289(22): 15566-76, 2014 May 30.
Article
en En
| MEDLINE
| ID: mdl-24742674
ABSTRACT
Platelet-activating factor (PAF), a potent proinflammatory lipid mediator, is synthesized rapidly in response to extracellular stimuli by the activation of acetyl-CoAlyso-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 Ca(2+)-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 PKCα-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 Vmax with minimal Km change. Our results offer an answer for the previously unknown mechanism of rapid PAF production.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Factor de Activación Plaquetaria
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Macrófagos Peritoneales
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Proteína Quinasa C-alfa
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Inflamación
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1-Acilglicerofosfocolina O-Aciltransferasa
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Biol Chem
Año:
2014
Tipo del documento:
Article