Signal transduction in EJ-H-ras-transformed cells: de novo synthesis of diacylglycerol and subversion of agonist-stimulated inositol lipid metabolism.
We examined the level of 1,2-diacylglycerol and inositol phosphates in normal and EJ-H-ras-transformed BALB/3T3 fibroblasts by prelabelling the cells with [3H]glycerol, [3H]inositol, [14C]glucose, [14C]arachidonic acid, and [14C]palmitic acid. Steady-state level of inositol phosphates, however, was the same in control and transformed cells. Diacyglycerol labelling by [14C]arachidonic acid was the same in control and transformed cells. Insulin dramatically increased diacylglycerol labeling by [14C]glucose in normal cells, whereas it did not affect ras-transformed fibroblasts. Neurotransmitter-induced inositol lipid turnover was greatly enhanced in ras-transformed cells; conversely, platelet-derived growth factor and thrombin-stimulated normal cells to a greater extent than transformed fibroblasts. Taken together these results suggest that ras transformation may induce multifarious effects on signal transduction: it may cause de novo synthesis of diacylglycerol and subversion of neurotransmitter and growth factor receptor coupling to inositol lipid metabolism.
Chiarugi
V P
VP
Laboratory of Molecular Biology, University of Firenze, Italy.
Magnelli
L
L
Pasquali
F
F
Basi
G
G
Ruggiero
M
M
D000818:Animals; D002461:Cell Line, Transformed; D004075:Diglycerides / Q000096:biosynthesis* / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects; D011905:Genes, ras; D005989:Glycerides / Q000096:biosynthesis*; D007294:Inositol / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D050356:Lipid Metabolism; D051379:Mice; D010712:Phosphatidic Acids / Q000378:metabolism; D015398:Signal Transduction
D004075:Diglycerides; D005989:Glycerides; D007295:Inositol Phosphates; D007328:Insulin; D010712:Phosphatidic Acids; D007294:Inositol