Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism for hydrogen peroxide (H2O2)-induced phospholipase D (PLD) activation was investigated in [3H]palmitic acid-labeled PC12 cells. In the presence of butanol, H2O2 caused a great accumulation of [3H]phosphatidylbutanol in a concentration- or time-dependent manner. However, treatment with H2O2 of cell lysates exerted no effect on PLD activity. Treatment with H2O2 had only a marginal effect on phospholipase C (PLC) activation. A protein kinase C (PKC) inhibitor, Ro 31-8220, did not inhibit but rather slightly enhanced H2O2-induced PLD activity. Thus, H2O2-induced PLD activation is considered to be independent of the PLC-PKC pathway in PC12 cells. In contrast, pretreatment with tyrosine kinase inhibitor herbimycin A, genistein, or ST638 resulted in a concentration-dependent inhibition of H2O2-induced PLD activation. Western blot analysis revealed several apparent tyrosine-phosphorylated protein bands after the H2O2 treatment and tyrosine phosphorylation of these proteins was inhibited by these tyrosine kinase inhibitors. Moreover, depletion of extracellular Ca2+ abolished H2O2-induced PLD activation and protein tyrosine phosphorylation. Extracellular Ca2+ potentiated H2O2-induced PLD activation in a concentration-dependent manner. Taken together, these results suggest that a certain Ca2+-dependent protein tyrosine kinase(s) somehow participates in H2O2-induced PLD activation in PC12 cells.
 ...
PMID:Hydrogen peroxide-induced phospholipase D activation in rat pheochromocytoma PC12 cells: possible involvement of Ca2+-dependent protein tyrosine kinase. 923 33

cAMP-induced Ca2+ influx in Dictyostelium follows two pathways: a G-protein-dependent pathway where influx is reduced by 50-70% in Galpha2 and Gbeta-negative strains and a heterotrimeric G-protein-independent pathway. Using a pharmacological approach, we found that phospholipase A2 (PLA2) is the target of both pathways. The products of PLA2 activity, arachidonic acid (AA) and palmitic acid, induced Ca2+ influx to a similar extent as cAMP. Half-maximal activation occurred at 3 microM AA and saturation at 10 microM AA. The response to AA was quantitatively similar throughout early differentiation and thus independent of cAMP-receptor concentration. Synergy experiments revealed that cAMP and AA acted through identical pathways. The PLA2-activating peptide, a peptide with sequence similarity to the G-protein beta-subunit, activated Ca2+ influx. The G-protein-independent pathway was sensitive to genistein but not to blockers of protein kinase C and other kinases, suggesting that tyrosine kinase may directly or indirectly activate PLA2 in this case.
 ...
PMID:Mechanism of cAMP-induced Ca2+ influx in Dictyostelium: role of phospholipase A2. 935 57

The individual and combined effects of the saturated diacylglycerol (DAG) dipalmitin (DP) and saturated or polyunsaturated unesterified fatty acids (PUFAs) on both the structure of phosphatidylcholine/phosphatidylserine (PC/PS; 4:1 mol/mol) bilayers and on protein kinase C (PKC) activity were studied using 2H nuclear magnetic resonance (NMR) and enzyme activity assays. In the absence of DP, PUFAs only slightly activated PKC whereas palmitic acid had no effect. In the absence of fatty acids, DP induced lateral phase separation of the bilayer into liquid-crystalline and gel phases. Under these conditions virtually all DP was sequestered into the gel phase and no activation of PKC was observed. The addition of polyunsaturated arachidonic or docosahexaenoic acids to the DP-containing bilayers significantly increased the relative amounts of DP and other lipid components in the liquid-crystalline phase, correlating with a dramatic increase in PKC activity. Furthermore, the effect was greater with PS, resulting in an enrichment of PS in the liquid-crystalline domains. In the presence of DP, palmitic acid did not decrease the amount of gel phase lipid and had no effect on PKC activity. The results explain the observed lack of PKC-activating capacity of long-chain saturated DAGs as due to the sequestration of DAG into gel domains wherein it is complexed with phospholipids and thus not available for the required interaction with the enzyme.
 ...
PMID:Effects of dipalmitoylglycerol and fatty acids on membrane structure and protein kinase C activity. 937 Apr 55

Silica may act as a stimulator of pulmonary inflammation and fibrosis. The effect of silica on phospholipase D (PLD) activity assayed as accumulation of [3H]phosphatidylethanol ([3H]PtdEt) was examined in [3H]palmitic acid-labeled primary cultures of rat alveolar macrophages. Silica induced a rapid accumulation of [3H]PtdEt in a time (0, 15, 30 and 45 min)- and concentration (0.5, 1.0, 2.5 and 5.0 mg/ml)-dependent manner indicating PLD activation. This silica-stimulated PLD activity was attenuated by the pretreatment with calcium chelator ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA) or/and 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid acetoxymethyl ester (BAPTA/AM) (EGTA: 54.3 +/- 8.6%, BAPTA/AM: 67.5 +/- 7.8% and EGTA + BAPTA/AM: 35.8 +/- 2.9, respectively). Also, silica-induced PLD activation was partially inhibited by the pretreatment with nonspecific phospholipase C (PLC) and PLD inhibitor (neomycin; 66.4 +/- 4.8%) or specific PLC inhibitor (U73122; 70.8 +/- 4.6%). Sphingosine as a protein kinase C (PKC) inhibitor did not change silica-induced PLD activity indicating that PKC might not play a role in PLD activation by silica. Based on these results, we concluded that a silica-stimulated phospholipase D activity is present in the rat alveolar macrophages and is predominantly regulated by PLC-mediated intracellular calcium.
 ...
PMID:Effect of silica on phospholipase D activity in rat alveolar macrophages. 970 5

Effects of fatty acids on translocation of the gamma- and epsilon-subspecies of protein kinase C (PKC) in living cells were investigated using their proteins fused with green fluorescent protein (GFP). gamma-PKC-GFP and epsilon-PKC-GFP predominated in the cytoplasm, but only a small amount of gamma-PKC-GFP was found in the nucleus. Except at a high concentration of linoleic acid, all the fatty acids examined induced the translocation of gamma-PKC-GFP from the cytoplasm to the plasma membrane within 30 s with a return to the cytoplasm in 3 min, but they had no effect on gamma-PKC-GFP in the nucleus. Arachidonic and linoleic acids induced slow translocation of epsilon-PKC-GFP from the cytoplasm to the perinuclear region, whereas the other fatty acids (except for palmitic acid) induced rapid translocation to the plasma membrane. The target site of the slower translocation of epsilon-PKC-GFP by arachidonic acid was identified as the Golgi network. The critical concentration of fatty acid that induced translocation varied among the 11 fatty acids tested. In general, a higher concentration was required to induce the translocation of epsilon-PKC-GFP than that of gamma-PKC-GFP, the exceptions being tridecanoic acid, linoleic acid, and arachidonic acid. Furthermore, arachidonic acid and the diacylglycerol analogue (DiC8) had synergistic effects on the translocation of gamma-PKC-GFP. Simultaneous application of arachidonic acid (25 MicroM) and DiC8 (10 microM) elicited a slow, irreversible translocation of gamma-PKC- GFP from the cytoplasm to the plasma membrane after rapid, reversible translocation, but a single application of arachidonic acid or DiC8 at the same concentration induced no translocation. These findings confirm the involvement of fatty acids in the translocation of gamma- and epsilon-PKC, and they also indicate that each subspecies has a specific targeting mechanism that depends on the extracellular signals and that a combination of intracellular activators alters the target site of PKCs.
 ...
PMID:Distinct effects of fatty acids on translocation of gamma- and epsilon-subspecies of protein kinase C. 978 59

Phospholipase D (PLD) is a phosphodiesterase that catalyses hydrolysis of phosphatidylcholine to produce phosphatidic acid and choline. In the presence of ethanol, PLD also catalyses the formation of phosphatidylethanol, which is a unique characteristic of this enzyme. Muscarinic receptor-induced changes in the activity of PLD were investigated in porcine tracheal smooth muscle by measuring the formation of [3H]phosphatidic acid ([3H]PA) and [3H]phosphatidylethanol ([3H]PEth) after labeling the muscle strips with [3H]palmitic acid. The cholinergic receptor agonist acetylcholine (Ach) significantly but transiently increased formation of both [3H]PA and [3H]PEth in a concentration-dependent manner (>105-400% vs. controls in the presence of 10(-6) to 10(-4) M Ach) when pretreated with 100 mM ethanol. The Ach receptor-mediated increase in PLD activity was inhibited by atropine (10(-6) M), indicating that activation of PLD occurred via muscarinic receptors. Activation of protein kinase C (PKC) by phorbol-12-myristate-13-acetate (PMA) increased PLD activity that was effectively blocked by the PKC inhibitors calphostin C (10(-8) to 10(-6) M) and GFX (10(-8) to 10(-6) M). Ach-induced increases in PLD activity were also significantly, but incompletely, inhibited by both GFX and calphostin C. From the present data, we conclude that in tracheal smooth muscle, muscarinic acetylcholine receptor-induced PLD activation is transient in nature and coupled to these receptors via PKC. However, PKC activation is not solely responsible for Ach-induced activation of PLD in porcine tracheal smooth muscle.
 ...
PMID:Activation of muscarinic receptors in porcine airway smooth muscle elicits a transient increase in phospholipase D activity. 1008 40

Prior studies have shown that 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3] plays a major role in resting zone chondrocyte differentiation and that this vitamin D metabolite regulates both phospholipase A2 and protein kinase C (PKC) specific activities. Arachidonic acid is the product of phospholipase A2 action and has been shown in other systems to affect a variety of cellular functions, including PKC activity. The aim of the present study was to examine the interrelationship between arachidonic acid and 24,25-(OH)2D3 on markers of proliferation, differentiation, and matrix production in resting zone chondrocytes and to characterize the mechanisms by which arachidonic acid regulates PKC, which was shown previously to mediate the rapid effects of 24,25-(OH)2D3 and arachidonic acid on these cells. Confluent, fourth passage resting zone cells from rat costochondral cartilage were used to evaluate these mechanisms. The addition of arachidonic acid to resting zone cultures stimulated [3H]thymidine incorporation and inhibited the activity of alkaline phosphatase and PKC, but had no effect on proteoglycan sulfation. In contrast, 24,25-(OH)2D3 inhibited [3H]thymidine incorporation and stimulated alkaline phosphatase, proteoglycan sulfation, and PKC activity. In cultures treated with both agents, the effects of 24,25-(OH)2D3 were reversed by arachidonic acid. The PKC isoform affected by arachidonic acid was PKCalpha; cytosolic levels were decreased, but membrane levels were unaffected, indicating that translocation did not occur. Arachidonic acid had a direct effect on PKC in isolated plasma membranes and matrix vesicles, indicating a nongenomic mechanism. Plasma membrane PKCalpha was inhibited, and matrix vesicle PKCzeta was stimulated; these effects were blocked by 24,25-(OH)2D3. Studies using cyclooxygenase and lipoxygenase inhibitors indicate that the effects of arachidonic acid are due in part to PG production, but not to leukotriene production. This is supported by the fact that H8-dependent inhibition of protein kinase A, which mediates the effects of PGE2, had no effect on the direct action of arachidonic acid but did mediate the role of arachidonic acid in the cell response to 24,25-(OH)2D3. Diacylglycerol does not appear to be involved, indicating that phospholipase C and/or D do not play a role. Gamma-linolenic acid, an unsaturated precursor of arachidonic acid, elicited a similar response in matrix vesicles but not plasma membranes, whereas palmitic acid, a saturated fatty acid, had no effect. These data suggest that arachidonic acid may act as a negative regulator of 24,25-(OH)2D3 action in resting zone chondrocytes.
 ...
PMID:Arachidonic acid directly mediates the rapid effects of 24,25-dihydroxyvitamin D3 via protein kinase C and indirectly through prostaglandin production in resting zone chondrocytes. 1038 91

In the present study we investigate the effect of exogenous sphingosine, sphingosine 1-phosphate and sphingosylphosphorylcholine on phospholipase D (PLD) activity in glioma C6 cells. The cells were prelabeled with [1-14C]palmitic acid and PLD-mediated synthesis of [14C]phosphatidylethanol was measured. Sphingosine 1-phosphate and sphingosylphosphorylcholine did not stimulate [14C]phosphatidylethanol formation either at low (0.1-10 microM) or high (25-100 microM) concentrations. On the other hand, sphingosine at concentrations of 100-250 microM strongly stimulated PLD activity as compared to the effect of phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), known as a PLD activator. The effect of TPA on PLD is linked to the activation of protein kinase C. The present study also shows that sphingosine additively enhances TPA-mediated PLD activity. This is in contrast to the postulated role of sphingosine as a protein kinase C inhibitor. These results demonstrate that in glioma C6 cells sphingosine not only affects PLD independently of its effect on protein kinase C, but also is unable to block TPA-mediated PLD activity.
 ...
PMID:Exogenous sphingosine 1-phosphate and sphingosylphosphorylcholine do not stimulate phospholipase D in C6 glioma cells. 1045 85

In has been found that sphingosine, propranolol, imipramine and phorbol ester (12-O-tetradecanoylphorbol-13-acetate, TPA) have a stimulatory effect on phospholipase D activity in glioma C6 cells. The cells were prelabelled with [1-(14)C]palmitic acid and phospholipase D-mediated synthesis of [(14)C]phosphatidylethanol was measured. The enhancing effect of TPA was almost completely blocked by a specific protein kinase C inhibitor, GF 109203X. In contrast, GF 109203X failed to inhibit the sphingosine, imipramine and propranolol stimulatory effects, indicating that their stimulation was independent of protein kinase C. The effect of TPA on phospholipase D was also blocked by imipramine and propranolol, whereas sphingosine additively potentiated TPA-mediated phospholipase D activity, both at shorter and longer (2-60 min) times of incubation. These results suggest that in glioma C6 cells, sphingosine is not only involved in a different phospholipase D activation than the TPA regulatory system, but also that it operates in a different compartment of the cell.
 ...
PMID:Different regulation of phospholipase D activity in glioma C6 cells by sphingosine, propranolol, imipramine and phorbol ester. 1088 69

GLP-1 (glucagon-like peptide-1) is a potent insulin secretagogue released from L cells in the intestine. The regulation of GLP-1 secretion has been described both in vivo and in vitro in several animal species, but data from human cellular models are lacking. For this purpose, factors and cell-signaling pathways regulating GLP-1 secretion were investigated in the NCI-H716 human intestinal cell line. After differentiation, these cells homogeneously produced 16.8 pmol GLP-1/mg protein with a basal release of 4.2% during a 2-h incubation period. Nutrients, such as palmitic acid, oleic acid, and meat hydrolysate, stimulated GLP-1 secretion in a dose-dependent manner, as did the cholinergic agonist carbachol and the neuromediator gastrin-releasing peptide. Along with stimulating GLP-1 release, gastrin-releasing peptide, like ionomycin, increased intracellular calcium levels. Activators of PKA and PKC were able to increase GLP-1 secretion in NCI-H716 cells. However, neither PKA activators nor meat hydrolysate increased proglucagon mRNA levels. These findings indicate that the NCI-H716 cell line constitutes a unique model to study the cellular mechanism of GLP-1 secretion in humans and suggest potential interspecies divergence in the regulation of proglucagon gene expression in enteroendocrine cells.
 ...
PMID:A human cellular model for studying the regulation of glucagon-like peptide-1 secretion. 1156 18


<< Previous 1 2 3 4 5 6 7 8 Next >>