ACTIVATION OF PHOSPHOLIPASE-D BY RAS PROTEINS IS INDEPENDENT OF PROTEIN-KINASE-C

Growth factors activate phospholipases, causing the generation of dive rse lipid metabolites with second messenger function. Among them, the phosphatidylcholine-preferring phospholipase D (PLD) has attracted gre at interest, since in addition to the transient activation by growth f actors stimulation, it is constitutively activated in some of the src- and ras-transformed cells investigated. To establish further the func tional relationship of ras oncogenes with PLD, we have investigated it s mechanism of regulation. Growth factors such as PDGF or FGF activate the PC-PLD enzyme by a common, PKC-dependent mechanism. By contrast, ras oncogenes activate the PC-PLD enzyme by a PKC-independent mechanis m. These results suggest the existence of at least two mechanisms for PLD activation, and ras oncogenes contribute to one of them. (C) 1996 Wiley-Liss, Inc.