Browsing by Author "Larrodera, Pilar"
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Item Activation of phosphatidylcholine-specific phospholipase C in cell growth and oncogene transformation.(Biochemical Society Transactions, 1989) Moscat, Jorge; Cornet, María E.; Díaz Meco, María T.; Larrodera, Pilar; López Alanon, Dulce; López Barahona, MónicaItem Kinetic evidence of a rapid activation of phosphatidylcholine hydrolysis by Ki-ras oncogene. Possible involvement in late steps of the mitogenic cascade.(Journal of Biological Chemistry, 1990) López Barahona, Mónica; Kaplan, P.; Cornet, M E; Díaz Meco, María T.; Larrodera, Pilar; Diaz-Laviada, I; Municio, A.; Moscat, JorgeA novel phospholipase C specific for phosphatidylcholine has been shown to be activated by several agonists. Also, recent evidence suggests that transformation mediated by the ras oncogene possibly involves the activation of this novel phospholipid degradative pathway which would account for the increased diacylglycerol levels associated with transformation. Here we use a mutant of Ki-ras which is temperature-sensitive for transformation to investigate the kinetics of activation of the phosphodiesterase-mediated turnover of phosphatidylcholine. Upon shift to the permissive temperature, products of the activated phosphatidylcholine-specific phospholipase C were detected by 30 min and reached maximal levels by 1-2 h. These results suggest that the product of the ras oncogene rapidly activates the phosphodiesteratic hydrolysis of phosphatidylcholine. Furthermore, the fact that at least 4 h are required for serum to activate this phospholipase C strongly suggests that the ras oncogene product might be involved in late steps of the mitogenic signaling cascade.Item Phospholipase C-mediated hydrolysis of phosphatidlycholine is an important step in PDGF-stimulated DNA synthesis.(Cell, 1990) Larrodera, Pilar; Cornet, María E.; Díaz Meco, María T.; Henrik Guddal, Per; Johansen, Terje; López Barahona, Mónica; Diaz-Laviada, Inés; Moscat, JorgeRecent evidence suggests the involvement of phosphatidylcholine (PC) hydrolysis both in the control of normal cell growth and in transformation. We show here that the simple exogenous addition of Bacillus cereus PC-hydrolyzing phospholipase C (PC-PLC) is sufficient to elicit a potent mitogenic response in Swiss 3T3 fibroblasts by a mechanism that is independent of protein kinase C. Our results on the additivity and synergism between B. cereus PC-PLC, PDGF, and insulin in the mitogenic response indicate that this novel phospholipid degradative pathway may be important in the mitogenic signaling cascade activated by PDGF.Item Phospholipase C-mediated hydrolysis of phosphatidylcholine is activated by muscarinic agonists.(Biochemical Journal, 1989) Díaz Meco, María T.; Larrodera, Pilar; López Barahona, Mónica; Cornet, María E.; Barreno, P.; Moscat, JorgeThe phospholipase C-catalysed breakdown of inositol-containing phospholipids is an important source of diacylglycerol in cells stimulated by several agonists. However, recent experimental evidence suggests that major phospholipids such as phosphatidylcholine may also be substrates of the phosphodiesteratic hydrolysis activated by hormones, growth factors and oncogene products. We show here that stimulation of muscarinic agonists activates the release of phosphocholine, which, along with diacylglycerol, is a metabolic product of phospholipase C-mediated hydrolysis of phosphatidylcholine. Fluoroaluminates mimic this muscarinic effect, strongly suggesting that carbachol-activated release of phosphocholine may be mediated by a guanine-nucleotide-binding protein. Evidence for this was obtained from experiments using permeabilized cells in which non-hydrolysable analogues of GTP activated phosphocholine release synergistically with carbachol.