Phospholipase A/Acyltransferase enzyme activity of H-rev107 inhibits the H-RAS signaling pathway

Background: h-rev107,also called hrasls3 or pla2g16,is a member of the hrev107 type ii tumor suppressor gene family. previous studies showed that h-rev107 exhibits phospholipase a/acyltransferase (pla/at) activity and downregulates h-ras expression. however,the mode of action and the site of inhibition of h-ras by h-rev107 are still unknown. results: our results indicate that h-rev107 was co-precipitated with h-ras and downregulated the levels of activated ras (ras-gtp) and elk1-mediated transactivation in epidermal growth factor-stimulated and h-ras-cotransfected htta cervical cancer cells. furthermore,an acyl-biotin exchange assay demonstrated that h-rev107 reduced h-ras palmitoylation. h-rev107 has been shown to be a pla/at that is involved in phospholipid metabolism. treating cells with the pla/at inhibitor arachidonyl trifluoromethyl ketone (aacocf3) or methyl arachidonyl fluorophosphate (mafp) alleviated h-rev107-induced downregulation of the levels of acylated h-ras. aacocf3 and mafp also increased activated ras and elk1-mediated transactivation in h-rev107-expressing htta cells following their treatment with epidermal growth factor. in contrast,treating cells with the acyl-protein thioesterase inhibitor palmostatin b enhanced h-rev107-mediated downregulation of acylated h-ras in h-rev107-expressing cells. palmostatin b had no effect on h-rev107-induced suppression of ras-gtp levels or elk1-mediated transactivation. these results suggest that h-rev107 decreases h-ras activity through its pla/at activity to modulate h-ras acylation. conclusions: we made the novel observation that h-rev107 decrease in the steady state levels of h-ras palmitoylation through the phospholipase a/acyltransferase activity. h-rev107 is likely to suppress activation of the ras signaling pathway by reducing the levels of palmitoylated h-ras,which decreases the levels of gtp-bound h-ras and also the activation of downstream molecules. our study further suggests that the pla/at activity of h-rev107 may play an important role in h-rev107-mediated ras suppression. © 2014 wang et al.; licensee biomed central ltd.