Arachidonic acid, a principal product of Rac-activated phospholipase A2, stimulates c-fos serum response element via Rho-dependent mechanism.
Previously, we have reported that phospholipase A2 (PLA2) is one of the major downstream targets by which Rac GTPase mediates the activation of c-fos serum response element (SRE) in response to agonists such as EGF [FEBS Lett. 407 (1997) 7-12]. Thus, the potential activity of arachidonic acid (AA), a principal product of Rac-activated PLA2, on c-fos SRE stimulation has been suggested. Here, we provide evidence about the biological activity of AA on c-fos SRE activation. Further, we observed that co-transfection with expression plasmid of either RhoN19, a dominant negative RhoA mutant, or botulinum C3 transferase which inhibits Rho via ADP ribosylation, selectively repressed AA- or Rac-induced SRE activation, suggesting that Rho activity is critical for the signaling cascade of 'Rac-PLA2-AA' to c-fos SRE. Thus, Rac signaling to the nucleus appears to be, at least partly, mediated by a Rho-linked pathway and this Rac-Rho signaling connection is mediated by AA. In accordance with the role of Rho as a potential mediator of AA signaling to the nucleus, AA induces a rapid translocation of RhoA.
Kim
B C
BC
Laboratory of Molecular and Cellular Genetics, Institute of Environment and Life Science, Hallym University, Chun-Cheon, South Korea.
Lim
C J
CJ
Kim
J H
JH
D036002:ADP Ribose Transferases / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology*; D015153:Blotting, Western; D001905:Botulinum Toxins; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005347:Fibroblasts; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D017930:Genes, Reporter / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010957:Plasmids / Q000235:genetics; D051381:Rats; D026362:Serum Response Factor; D015398:Signal Transduction; D014162:Transfection; D020744:rac GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D026362:Serum Response Factor; D016718:Arachidonic Acid; D004815:Epidermal Growth Factor; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D010741:Phospholipases A; D054467:Phospholipases A2; D001905:Botulinum Toxins; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020744:rac GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein