Angiotensin stimulates phosphatidylcholine synthesis via a pathway involving diacylglycerol, protein kinase C, ERK1/2, and CTP:phosphocholine cytidylyltransferase

2006 ◽  
Vol 1761 (2) ◽  
pp. 272-279 ◽  
Author(s):  
Theresa E. Kitos ◽  
Chrystal M.Y. Choi ◽  
Rosemary B. Cornell
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Ctp:Phosphocholine Cytidylyltransferase ◽  
Kinase C ◽  
Phosphatidylcholine Synthesis

scholarly journals Stimulation of the hydrolysis of phosphatidylinositol 4,5-bisphosphate and phosphatidylcholine by endothelin, a complete mitogen for Rat-1 fibroblasts

1990 ◽  
Vol 272 (3) ◽  
pp. 761-766 ◽  
Author(s):  
E E MacNulty ◽  
R Plevin ◽  
M J O Wakelam
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Endothelin 1 ◽  
Kinase C ◽  
Choline Phosphate ◽  
Rapid Generation ◽  
Endothelin 3 ◽  
Hydrolysis Of ◽  
Phosphatidylcholine Synthesis ◽  
Stimulation Of

The mitogenic activity of endothelin and its ability to stimulate PtdIns(4,5)P2 and phosphatidylcholine turnover in Rat-1 fibroblasts was studied. Stimulated incorporation of [3H]thymidine occurred in the absence of any other added growth factors. The endothelins stimulated rapid generation of both Ins(1,4,5)P3 and choline. Endothelin-1 and endothelin-2 were equipotent in stimulating both responses, but endothelin-3 was less potent. Endothelin-1-stimulated Ins(1,4,5)P3 generation reached a maximum at 5 s and then declined; however, the response was long-lived, with a 4.5-fold elevation over basal still observed after 15 min. Endothelin-stimulated choline generation was observed with no increase in choline phosphate; indeed, the apparent level of this metabolite fell after 30 min of stimulation, presumably due to the observed stimulation of phosphatidylcholine synthesis. The endothelin-stimulated increase in choline generation was abolished in cells where protein kinase C was down-regulated. However, endothelin-stimulated choline generation was greater than that observed in response to a protein kinase C-activating phorbol ester, raising the possibility that the peptide activates phospholipase D by both protein kinase C-dependent and -independent mechanisms.

scholarly journals 1,2-Diacylglycerols overcome cyclic AMP-mediated inhibition of phosphatidylcholine synthesis in GH3 pituitary cells

1990 ◽  
Vol 267 (1) ◽  
pp. 17-22 ◽  
Author(s):  
R N Kolesnick
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Phorbol Esters ◽  
Pituitary Cells ◽  
Dibutyryl Cyclic Amp ◽  
Kinase C ◽  
Low Concentrations ◽  
High Concentrations ◽  
Phosphatidylcholine Synthesis

Previous studies showed that phorbol esters and thyrotropin-releasing hormone (TRH) stimulated phosphatidylcholine synthesis via protein kinase C in GH3 pituitary cells [Kolesnick (1987) J. Biol. Chem. 262, 14525-14530]. In contrast, 1,2-diacylglycerol-stimulated phosphatidylcholine synthesis appeared independent of protein kinase C. The present studies compare phosphatidylcholine synthesis stimulated by these agents with inhibition via the cyclic AMP system. The potent phorbol ester phorbol 12-myristate 13-acetate (PMA, 10 nM) increased [32P]Pi incorporation into phosphatidylcholine at 30 min to 159 +/- 6% of control. The adenylate cyclase activator cholera toxin (CT; 10 nM) and the cyclic AMP analogue dibutyryl cyclic AMP (1 mM) abolished this effect. CT similarly abolished TRH-induced phosphatidylcholine, but not phosphatidylinositol, synthesis. This is the first report of inhibiton of receptor-mediated phosphatidylcholine synthesis by the cyclic AMP system. The 1,2-diacylglycerol 1,2-dioctanoylglycerol (diC8) also stimulated concentration-dependent phosphatidylcholine synthesis. DiC8 (3 micrograms/ml) induced an effect quantitatively similar to that of maximal concentrations of PMA and TRH, whereas a maximal diC8 concentration (30 micrograms/ml) stimulated an effect 3-4-fold greater than these other agents. CT decreased the effect of diC8 (3 micrograms/ml) by 80%. Higher diC8 concentrations overcame the CT inhibition. Similar results were obtained with dibutyryl cyclic AMP. Additional differences were found between low and high concentrations of diC8. Low concentrations of diC8 failed to induce additive phosphatidylcholine synthesis with maximal concentrations of PMA, whereas high concentrations were additive. Hence, low concentrations of 1,2-diacylglycerols appear to be regulated similarly to phorbol esters, and higher concentrations appear to act via a pathway unavailable to phorbol esters.

CTP:phosphocholine cytidylyltransferase inhibition by ceramide via PKC-α, p38 MAPK, cPLA2, and 5-lipoxygenase

2001 ◽  
Vol 281 (1) ◽  
pp. L108-L118 ◽  
Author(s):  
Shanjana Awasthi ◽  
Jeevalatha Vivekananda ◽  
Vibhudutta Awasthi ◽  
Dolphin Smith ◽  
Richard J. King
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
De Novo ◽  
Cell Types ◽  
Companion Paper ◽  
Mitogen Activated Protein Kinase ◽  
Ctp:Phosphocholine Cytidylyltransferase ◽  
Kinase C ◽  
Tnf Α ◽  
Mitogen Activated Protein

In a companion paper (Vivekananda J, Smith D, and King RJ. Am J Physiol Lung Cell Mol Physiol 281: L98–L107, 2001), we demonstrated that tumor necrosis factor (TNF)-α inhibited the activity of CTP:phosphocholine cytidylyltransferase (CT), the rate-limiting enzyme in the de novo synthesis of phosphatidylcholine (PC), and that its actions were likely exerted through a metabolite of sphingomyelin. In this paper, we explore the signaling pathway employed by TNF-α using C2 ceramide as a cell-penetrating sphingolipid representative of the metabolites induced by TNF-α. We found that in H441 cells, as reported in other cell types, cytosolic phospholipase A2 (cPLA2) is activated by TNF-α. We also observed that the inhibiting action of C2ceramide on CT requires protein kinase C-α, p38 mitogen-activated protein kinase, and cPLA2. The actions of C2ceramide on CT activity can be duplicated by adding 2 μM lysoPC to these cells. Furthermore, we found that the effects of C2ceramide are dependent on 5-lipoxygenase but that cyclooxygenase II is unimportant. We hypothesize that CT activity is inhibited by the lysoPC generated as a consequence of the activation of cPLA2 by protein kinase C-α and p38 mitogen-activated protein kinase. The other product of the activation of cPLA2, arachidonic acid, is a substrate for the synthesis of leukotrienes, which raise intracellular Ca2+ levels and complete the activation of cPLA2.

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