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Signal transduction in EJ‐H‐ ras ‐transformed cells: De novo synthesis of diacylglycerol and subversion of agonist‐stimulated inositol lipid metabolism
Author(s) -
Chiarugi Vincenzo P.,
Magnelli Lucia,
Pasquali Franca,
Basi Gabriele,
Ruggiero Marco
Publication year - 1989
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(89)80904-4
Subject(s) - diacylglycerol kinase , inositol , diglyceride , arachidonic acid , biology , signal transduction , biochemistry , second messenger system , diacylglycerol lipase , endocrinology , microbiology and biotechnology , medicine , receptor , protein kinase c , fatty acid , enzyme
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 [ 3 H]glycerol, [ 3 H]inositol, [ 14C ]glucose, [ 14 C]arachidonic acid, and [ 14 ]palmitic acid. Steady‐state level of diacylglycerol was increased in ras ‐transformed cells prelabelled with radioactive glycerol, glucose and palmitic acid. Steady‐state level of inositol phosphates, however, was the same in control and transformed cells. Diacylglycerol labelling by [ 14 C]arachidonic acid was the same in control and transformed cells. Insulin dramatically increased diacylglycerol labelling by [ 14 C]glucose in normal cells, wheras 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.