Lysophosphatidylcholine stimulates activator protein 1 and the c-Jun N-terminal kinase activity

J Biol Chem. 1997 May 23;272(21):13683-9. doi: 10.1074/jbc.272.21.13683.

Abstract

Lysophosphatidylcholine (lyso-PC), a natural lipid generated through the action of phospholipase A2 on membrane phosphatidylcholine, has been implicated in atherogenesis and the inflammatory process. In vitro studies have established a role for lyso-PC in modulation of gene expression and other cellular responses including differentiation and proliferation. There is also evidence that lyso-PC may act as an intracellular second messenger transducing signals elicited from membrane-associated receptors. The mechanisms behind the diverse activities of lyso-PC are poorly understood. We report, in this study, that treatment of cultured cells with exogenous lyso-PC, at nontoxic concentrations, potently induced activator protein-1 (AP-1) DNA binding and transcriptional activity independent of well known AP-1 activators, protein kinase C or mitogen-activated protein kinases ERK1 and ERK2. Lyso-PC also activated the c-Jun N-terminal kinase (JNK/SAPK), a recently characterized member of the mitogen-activated protein kinase family, known to activate AP-1. The stimulated JNK and AP-1 activities probably mediate or contribute to some bioactive effects of lyso-PC.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • DNA / metabolism
  • Enzyme Activation / drug effects
  • Genes, jun / drug effects
  • HeLa Cells
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • Lysophosphatidylcholines / pharmacology*
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases*
  • Protein Kinase C / metabolism
  • Rats
  • Signal Transduction / drug effects
  • Transcription Factor AP-1 / metabolism*
  • Transcription, Genetic / drug effects

Substances

  • Lysophosphatidylcholines
  • Transcription Factor AP-1
  • DNA
  • Protein Kinase C
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases