Lysophosphatidylcholine stimulates activator protein 1 and the c-Jun N-terminal kinase activity.
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.
Fang
X
X
Division of Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Gibson
S
S
Flowers
M
M
Furui
T
T
Bast
R C
RC
Mills
G B
GB
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
D008244:Lysophosphatidylcholines; D018808:Transcription Factor AP-1; D004247:DNA; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases