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 activati on 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 a rachidonic acid (AA), a principal product of Rac-activated PLA(2), on c-fos SRE stimulation has been suggested. Here, we provide evidence ab out the biological activity of AA on c-fos SRE activation. Further, we observed that co-transfection with expression plasmid of either RhoN1 9, a dominant negative RhoA mutant, or botulinum C3 transferase which inhibits Rho via ADP ribosylation, selectively repressed AA-or Pac-ind uced 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-lin ked pathway and this Rac-Rho signaling connection is mediated by AA. I n accordance with the role of Rho as a potential mediator of AA signal ing to the nucleus, kil induces a rapid translocation of RhoA. (C) 199 7 Federation of European Biochemical Societies.