Arachidonic acid, a principal product of Rac-activated phospholipase A(2), stimulates c-fos serum response element via Rho-dependent mechanism

Previously, we have reported that phospholipase Az (PLA(2)) is one of the major downstream targets by which Rac GTPase mediates the activation of c-fas 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 PLA(2), 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 Pac-induced SRE activation, suggesting that Rho activity is critical for the signaling cascade of 'Rac-PLA(2)-AA' to c-fos SRE. Thus, Pac signaling to the nucleus appears to be, at least partly, mediated by it 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, kil induces a rapid translocation of RhoA. (C) 1997 Federation of European Biochemical Societies.