S,gnal transducuon reduced by epidermal growth factor (EGF) vm ,ts receptor revolves two second messengers, chacylglycerol (DG) and momtol msphosphate, both products of phosphandylmo~to|-specdic phosphohpase C wluch seem to pamctpate m the regulauon of cellular prohferauon by EGF We observed that A431 cells and HeL~ cells m response to EGF accumulate substanual amounts of phosphauchc actd (PA), the potenual product of DG kmase However, PA appears earher and stays longer elevated than expected from DG avadabxhty thus rinsing the poss~bd~ty of an EGF-mduced acuvatxon of a phosphohpase D (PLD) In the presence of prm=ry alcohols PLD effects the phosphandyl transfer reacuon producmg PA-alcohol, a reacuon known to be excluszvely ~ by PLD m mtact cells A431 cells and cells prelabeled w~th [14C]-oleate produce m the presence of ethanol (0 5%) or l-butanol (0 2%) substanual amounts of labeled PA-alcohol m response to EGF These results mchcate that acuvauon of PLD had occurred Acuvauon of PLD may x~present a novel mgnal transducing pathway wluch may pamctpate m the regulauon of cell prohferauon by EGF -a hypothes~s presently mvesugated m thts laboratory Supported by the Deutsche Forschungsgememschaft.