Evidence for role of phospholipase A2 in phosphatidic acid-induced signaling to c-fos serum response element activation.
The activity of exogenous phosphatidic acid (PA) to transactivate c-fos serum response element (SRE) was investigated by transient transfection analysis. Incubation of Rat-2 fibroblast cells with exogenous PA caused a stimulation of c-fos SRE-linked luciferase activity in a dose- and time-dependent manner. The SRE stimulation by PA was dramatically reduced by either pre-treatment with mepacrine, an inhibitor of phospholipase A2 (PLA2), or co-transfection with antisense cytosolic phospholipase A2 (cPLA2) oligonucleotide, whereas lysophosphatidic acid (LPA)-induced SRE activation was not affected. Consistent with this specific requirement for PLA2 by PA, the translocation of cPLA2 protein was rapidly induced followed by PA treatment. Together, these results suggest that PLA2, especially cPLA2, plays a critical role in the nuclear signaling cascade of PA in Rat-2 fibroblast cells.
Kim
B C
BC
Department of Molecular and Cellular Genetics, Hallym University, Chun-Cheon, Kangwon-do, Korea.
Ha
K S
KS
Park
J B
JB
Kim
J H
JH
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D008246:Lysophospholipids / Q000494:pharmacology; D009687:Nuclear Proteins / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000494:pharmacology*; D010741:Phospholipases A / Q000502:physiology*; D054467:Phospholipases A2; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D026362:Serum Response Factor; D015398:Signal Transduction / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects*; D014162:Transfection / Q000235:genetics
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D008246:Lysophospholipids; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D010712:Phosphatidic Acids; D026362:Serum Response Factor; D004815:Epidermal Growth Factor; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine