c-Fos, a transcription factor. associates to endoplasmic reticulum and modulates phospholipid biosynthesis. Its surface thermodynamic properties allow it to differentially interact with phospholipid monolayers with a selective dependence on the lipid polar head group and the lateral Surface pressure. We explored the c-Fos ability to modulate phospholipid degradation by phospholipases (ppPLA(2). Bacillus cereus PLC. and sphingomyelinase) using the monolayer technique. Experiments conducted under constant packing conditions show that c-Fos modulates phospholipase activity in a finely tuned way, depending on the membrane intermolecular packing. Surface lateral pressures above 12-16 mN/m induce c-Fos to activate phospholipase A(2) and sphingomyelinase, and abolish phospholipase C activity. The effects of c-Fos on other steps of the catalytic process. lag-time and extent, are synergic with those on activity. We show for the first time that c-Fos participates in modulating phospholipid degradation and that it can affect the fort-nation of lipid second messenger products by PLA(2). PLC. and sphingomyelinase. (C) 2002 Elsevier Science (USA). All rights reserved.