Distinct signaling pathways mediate induction of c-fos by PGE2 in glomerular mesangial cells.
Prostanoids induce expression of several immediate-early genes but the molecular mechanisms underlying these responses remain poorly characterized. We have studied induction of the proto-oncogenc c-fos by PGE2 in mesangial cells as a model of gene regulation by prostanoids. PGE2 induced marked and transient accumulation of c-fos mRNA. Induction of c-fos by PGE2 and TxA2 did not correlate with induction of phospholipase C. Addition of exogenous cAMP failed to induce c-fos mRNA, suggesting that activation of an EP2 receptor linked to adenylate cyclase did not account for induction of c-fos by PGE2. These data contrast with previous experiments in NIH 3T3 cells where PGE2 induced c-fos by a cAMP-dependent mechanism. We further showed that PGE2 induces the c-fos gene by direct activation of the serum response element. Taken together these experiments provide evidence for a pathway linking a PGE2 receptor on the plasma membrane to transcriptional activation in the nucleus.
Simonson
M S
MS
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Herman
W H
WH
Dunn
M J
MJ
D016475:3T3 Cells; D000818:Animals; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D004790:Enzyme Induction; D016762:Genes, fos / Q000187:drug effects*; D005920:Glomerular Mesangium / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects*; D013928:Thromboxane A2 / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D010738:Type C Phospholipases / Q000096:biosynthesis
D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011994:Recombinant Proteins; D013928:Thromboxane A2; D015500:Chloramphenicol O-Acetyltransferase; D010738:Type C Phospholipases