Activation of phospholipase D by ras proteins is independent of protein kinase C.
Growth factors activate phospholipases, causing the generation of diverse lipid metabolites with second messenger function. Among them, the phosphatidylcholine-preferring phospholipase D (PLD) has attracted great interest, since in addition to the transient activation by growth factors stimulation, it is constitutively activated in some of the src- and ras-transformed cells investigated. To establish further the functional relationship of ras oncogenes with PLD, we have investigated its 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 mechanism. These results suggest that existence of at least two mechanisms for PLD activation, and ras oncogenes contribute to one of them.
del Peso
L
L
Instituto de Investigaciones Biomédicas, Madrid, Spain.
Hernández
R
R
Esteve
P
P
Lacal
J C
JC
D016475:3T3 Cells; D000818:Animals; D000077214:Becaplermin; D002461:Cell Line, Transformed; D002794:Choline / Q000032:analysis; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D011905:Genes, ras; D016391:Genes, src; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D051379:Mice; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010739:Phospholipase D / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011493:Protein Kinase C / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D020574:Proto-Oncogene Proteins c-sis; D018631:ras Proteins / Q000502:physiology*
D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D010739:Phospholipase D; D018631:ras Proteins; C088060:bisindolylmaleimide; D002794:Choline