Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.4.3 (phospholipase C)
18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because receptors, G proteins, and phospholipases all exist within a membrane lipid environment, it is not unreasonable to assume that an enzyme capable of changing the lipid environment can affect the coupling relationship among these signal transducing components. Our previous study showed that a muscarinic acetylcholine receptor regulates phosphatidylcholine phospholipase D via a G protein in brain. We demonstrate here that phosphatidylinositol phospholipase C and phosphatidylcholine phospholipase D are simultaneously activated within 15 s by muscarine in the presence of 1 microM GTP gamma S. More important, inhibition of phospholipase D by zinc attenuated carbamylcholine-induced activation of phospholipase C by 30%. Our additional evidence strongly indicates that the receptor-regulated phospholipase D plays an important modulatory role in agonist-stimulated phosphatidylinositol breakdown. This modulatory effect may be achieved by changing the membrane microenvironment in which phospholipase C and phosphoinositol lipids reside, consequently amplifying the inositol phospholipid signaling process. Our results lead us to postulate that the potential interaction between two different signaling pathways may provide a cell with intracellular coordination and enable the cell to achieve functional responses.
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PMID:Cross-talk between receptor-regulated phospholipase D and phospholipase C in brain. 200 91

As assessed by incorporation into liposomes and by adsorption to octyl-Sepharose, the integrity of the membrane anchor for the purified tetrameric forms of alkaline phosphatase from human liver and placenta was intact. Any treatment that resulted in a dimeric enzyme precluded incorporation and adsorption. An intact anchor also allowed incorporation into red cell ghosts. The addition of hydrophobic proteins inhibited incorporation into liposomes to varying degrees. Alkaline phosphatase was 100% releasable from liposomes and red cell ghosts by a phospholipase C specific for phosphatidylinositol. There was no appreciable difference in the rates of release of placental and liver alkaline phosphatases, although both were approximately 250 x slower in liposomes and 100 x slower in red cell ghosts than the enzyme's release from a suspension of cultured osteosarcoma cells. Both enzymes were released by phosphatidylinositol phospholipase C as dimers and would not reincorporate or adsorb to octyl-Sepharose. However, the enzyme incorporated, resolubilized by Triton X-100, and cleansed of the detergent by butanol treatment was tetrameric by gradient gel electrophoresis, was hydrophobic, and could reincorporate into fresh liposomes. A monoclonal antibody to liver alkaline phosphatase inhibited the enzyme's incorporation into liposomes, and abolished its release from liposomes and its conversion to dimers by phosphatidylinositol phospholipase C.
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PMID:Incorporation of human liver and placental alkaline phosphatases into liposomes and membranes is via phosphatidylinositol. 217 99

Bacillus cereus secretes three different phospholipases C. We studied the effect of Pi levels in the growth medium on the production of these exoenzymes. Production of both phosphatidylcholine-preferring phospholipase C and sphingomyelinase C was repressed by Pi in the growth medium, whereas production of phosphatidylinositol phospholipase C was unaffected. We also found that B. cereus secretes a phosphate-repressed alkaline phosphatase activity. Together with a previously reported highly efficient, active uptake system for Pi, these three phosphate-repressed exoenzyme activities seem to be part of a phosphate retrieval mechanism that operates under growth-limiting concentrations of Pi. In natural soil systems, which are the natural habitats of B. cereus, the scarcity of Pi is the major growth-limiting factor. A phosphate-repressed metalloprotease activity was also detected in culture supernatants of B. cereus. It is unclear whether this exoenzyme activity also participates in the proposed phosphate-scavenging system.
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PMID:Apparent phosphate retrieval system in Bacillus cereus. 250 29

Glucocorticoids induce the synthesis of a family of phospholipase inhibitory proteins, lipocortins. This family of lipocortins includes inhibitory proteins on phospholipase A2, phospholipase C and phosphatidylinositol phospholipase C. Hence, glucocorticoids reduce the formation of prostaglandins and leukotrienes by inhibiting cellular phospholipases, enzymes that degrade membrane phospholipids to release arachidonic acid, a precursor. The induction by glucocorticoids requires 1 h for the synthesis of mRNA and 5 h for the synthesis of proteins in various tissues and cells. However, glucocorticoids often exert their suppressive effects before the induction of lipocortins. This is now attributed to the nonenzymic formation of the adducts between glucocorticoids and lipocortins. These adducts are easily inserted into the membranes and more resistant to digestion of proteases, thus being more biologically potent with respect to suppression of the release of arachidonic acid, a precursor of prostaglandins and leukotrienes.
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PMID:Regulation of prostaglandin formation by glucocorticoids and their second messenger, lipocortins. 296 39

The isometric tension developed in response to diffuse application of acetylcholine was recorded in intact soleus muscles of the rat. Purified bacterial phospholipases of the C type, which hydrolyse either phosphatidylinositol or phosphatidylcholine, increased the acetylcholine contracture responses of the muscles. Sciatic nerve cytosol which had been purified over 8-fold with respect to phosphatidylinositol phospholipase C activity also increased these responses. The effect of phospholipase C on the miniature endplate potentials and neurally evoked endplate potentials was investigated in mouse diaphragm in vitro. The amplitude of both the miniature endplate potentials and the evoked endplate potentials was increased by the enzyme. The resting membrane potential, the effective input resistance and the frequency of miniature endplate potentials were not significantly altered by concentrations of the enzyme which increased the endplate responses. It is suggested that phospholipase C could have a trophic role at the neuromuscular junction.
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PMID:Action of phospholipase C at the neuromuscular junction in rodent skeletal muscles. 369 54

Glycosylphosphatidylinositol phospholipase C (GPI-PLC) from Trypanosoma brucei and phosphatidylinositol phospholipase C (PI-PLC) from Bacillus sp. both cleave glycosylphosphatidylinositols (GPIs). However, phosphatidylinositol, which is efficiently cleaved by PI-PLC, is a very poor substrate for GPI-PLC. We examined GPI-PLC substrate requirements using glycoinositol analogs of GPI components as potential inhibitors. Glucosaminyl (alpha 1-->6)-D-myo-inositol (GlcN(alpha 1-->6)Ins), GlcN(alpha 1-->6)Ins 1,2-cyclic phosphate, GlcN(alpha 1-->6)-2-deoxy-Ins, and GlcN(alpha 1-->6)Ins 1-dodecyl phosphonate inhibited GPI-PLC. GlcN(alpha 1-->6)Ins was as effective as Man-(alpha 1-->4)GlcN(alpha 1-->6)Ins; we surmise that GlcN(alpha 1-->6)Ins is the crucial glycan motif for GPI-PLC recognition. Inhibition by GlcN(alpha 1-->6)Ins 1,2-cyclic phosphate suggests product inhibition since GPIs cleaved by GPI-PLC possess a GlcN(alpha 1-->6)Ins 1,2-cyclic phosphate at the terminus of the residual glycan. The effectiveness of GlcN(alpha 1-->6)-2-deoxy-Ins indicates that the D-myo-inositol (Ins) 2-hydroxyl is not required for substrate recognition, although it is probably essential for catalysis. GlcN(alpha 1-->6)-2-deoxy-L-myo-inositol, unlike GlcN(alpha 1-->6)-2- deoxy-Ins, had no effect on GPI-PLC; hence, GPI-PLC can distinguish between the two enantiomers of Ins. Surprisingly, GlcN(alpha 1-->6)Ins 1,2-cyclic phosphate was not a potent inhibitor of Bacillus cereus PI-PLC, and GlcN(alpha 1-->6)Ins had no effect on the enzyme. However, both GlcN(alpha 1-->6)Ins 1-phosphate and GlcN(alpha 1-->6)Ins 1-dodecyl phosphonate were competitive inhibitors of PI-PLC. These observations suggest an important role for a phosphoryl group at the Ins 1-position in PI-PLC recognition of GPIs. Other studies indicate that abstraction of a proton from the Ins 2-hydroxyl is not an early event in PI-PLC cleavage of GPIs. Furthermore, both GlcN(alpha 1-->6)-2-deoxy-Ins 1-phosphate and GlcN(alpha 1-->6)-2-deoxy-L- myo-inositol inhibited PI-PLC without affecting GPI-PLC. Last, the aminoglycoside G418 stimulated PI-PLC, but had no effect on GPI-PLC. Thus, these enzymes represent mechanistic subclasses of GPI phospholipases C, distinguishable by their sensitivity to GlcN(alpha 1-->6)Ins derivatives and aminoglycosides. Possible allosteric regulation of PI-PLC by GlcN(alpha 1-->6)Ins analogs is discussed.
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PMID:Glycan requirements of glycosylphosphatidylinositol phospholipase C from Trypanosoma brucei. Glucosaminylinositol derivatives inhibit phosphatidylinositol phospholipase C. 785 13

We have previously shown that an ectoenzyme, NAD glycohydrolase (NADase) could be solubilized by treatment with bacterial phosphatidylinositol phospholipase C (PIPLC). However, it is unknown whether endogenous PIPLC can cleave this ectoenzyme. In this study, we used mouse peritoneal exudate macrophages which have been known to have relatively high activity of NADase. The results show that release of ecto-NADase was markedly increased when mouse peritoneal macrophages were costimulated with interferon-gamma (IFN-gamma) and bacterial lipopolysaccharide (LPS), compared to unstimulated cells. This increase was preceded by markedly enhanced activity of endogenous glycosylphosphatidylinositol phospholipase C (GPIPLC). The cross-reacting determinant (CRD) of the glycosylphosphatidylinositol anchor in released NADase from activated macrophages was detected by immunoblotting with anti-CRD antibody. Taken together, ecto-NADase is release from peritoneal exudate macrophages during IFN-gamma/LPS-induced activation and endogenous GPIPLC is involved in the NADase release from the activated macrophages.
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PMID:Glycosylphosphatidylinositol-anchored NAD glycohydrolase is released from peritoneal macrophages activated by interferon-gamma and lipopolysaccharide. 799 54

Rat liver cells were homogenized and subsequently fractionated by a simplified method based on microfiltration, which proved to give a high recovery of membrane-bound phosphatidylinositol phospholipase C (PI-PLC) activity. The effects of insulin, acetylcholine (AC), epinephrine (EN) and bacterial phospholipase C (bPLC) on the PI-PLC activity were studied after in vitro treatment of isolated membranes or after in situ application in rat liver. A dose-dependent increase of membranous PI-PLC (up to 3-fold) and corresponding 36 to 72% decline of the cytosolic activity were established upon treatment with supraphysiological doses of insulin or with bPLC, respectively. AC induced a biphasic response with a maximal stimulation in the micromolar range. On the other hand EN promoted a slight but significant dose-dependent inhibition of PI-PLC in both cytosol and membranes. Sodium fluoride was also a potent inhibitor of the membrane-associated PI-PLC with an EC50 value of about 5 mM. The combined assay with NaF and EN revealed no additivity between their inhibitory effects, suggesting a common step in the mechanism(s) of inhibition caused by the two agents. The stimulatory effects of insulin and AC were partially reduced by soluble cytosolic factors, which still remain to be identified. When insulin and AC were applied in combination in the presence of cytosol, this resulted in a 56% inhibition of PI-PLC below the control level.
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PMID:Altered levels of phosphatidylinositol phospholipase C activity in rat liver cells in response to insulin, epinephrine, acetylcholine and bacterial phospholipase C. 838 21

Tc-85, an 85-kDa surface glycoprotein specific for the trypomastigote stage of Trypanosoma cruzi, has been implicated in the invasion of host cells by the parasite. Radioactive palmitic acid was incorporated into Tc-85 immunoprecipitated from the culture medium with the H1A10 monoclonal antibody, suggesting that shedding occurs with Tc-85 bearing its GPI anchor. In contrast to the glycoprotein remaining in the parasites, the glycosylphosphatidylinositol moiety in shed Tc-85 is resistant to phosphatidylinositol phospholipase C and becomes susceptible to the enzyme following alkali treatment. An alkylglycerol was identified by thin layer chromatography of an ether extract after the enzymatic reaction. Resistance to cleavage by phospholipase C is due to fatty acid esterification of the inositol residue in shed Tc-85. This is the first example of inositol modification in anchors from a glycoprotein of Trypanosoma cruzi.
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PMID:Trypanosoma cruzi: the Tc-85 surface glycoprotein shed by trypomastigotes bears a modified glycosylphosphatidylinositol anchor. 863 80

The glycosylphosphatidylinositol phospholipase C (GPI-PLC) from Trypanosoma brucei is particularly effective in hydrolysing the GPI-anchors of some proteins. The enzyme is inhibited by Zn2+ and p-chloromercurylphenylsulphonic acid, both of which can act as sulphydryl reagents, suggesting that a cysteine residue may be important in catalysis. Single cysteine to serine mutants have been produced for all eight cysteines in GPI-PLC; all the mutants were fully active in vitro and were still susceptible to p-chloromercurylphenylsulphonic acid inhibition. In contrast, a single histidine 34 to glutamine mutation totally inactivated GPI-PLC. The histidine was chosen after a sequence alignment with the Bacillus cereus phosphatidylinositol phospholipase C (PI-PLC) suggested a conservation of active site residues, including histidine 34 which is central to the proposed reaction mechanism (Heinz D.W., Ryan M., Bullock T.L., Griffith O.H. EMBO J 1995;14:3855-3863). The results suggest that the GPI-PLC and bacterial PI-PLCs have conserved active sites and that the inhibition of GPI-PLC by sulphydryl reagents can occur through more than one residue.
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PMID:Mutagenesis study of the glycosylphosphatidylinositol phospholipase C of Trypanosoma brucei. 947 90


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