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)

We have isolated and characterized a developmentally regulated gene in Trypanosoma brucei, arbitrarily termed BS2. BS2 mRNA is substantially more abundant in bloodstream-form trypanosomes than in procyclic culture forms. Its nucleotide sequence reveals a single contiguous open-reading frame of 497 codons and is predicted to encode a protein of approximately 55.5 kilodaltons. A search of the NBRF protein data base revealed that within the predicted amino acid sequence are two of the evolutionarily conserved redox sites typified by thioredoxin of bacteria. Of this family of proteins, the recently sequenced rat genes encoding protein-disulfide isomerase (PDI) and form I phosphoinositide-specific phospholipase C (PIPLC) showed homology extending over the length of all three proteins (i.e., between BS2, PDI, and PIPLC). Although this homology includes the acidic C-terminus characteristic of proteins localized to the lumen of the endoplasmic reticulum, the BS2 product is predicted to possess multiple sites for N-linked glycosylation while PDI and PIPLC have none. Possible roles of the BS2 gene product in trypanosome physiology are discussed.
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PMID:A developmentally regulated gene of trypanosomes encodes a homologue of rat protein-disulfide isomerase and phosphoinositol-phospholipase C. 255 75

The vesicular stomatitis virus glycoprotein forms noncovalently linked trimers in the endoplasmic reticulum before being transported to the Golgi apparatus. The experiments reported here were designed to determine if the extracellular domain of the glycoprotein contains structural information sufficient to direct trimer formation. To accomplish this, we generated a construct encoding G protein with the normal transmembrane and anchor sequences replaced with the sequence encoding 53 C-terminal amino acids from the Thy-1.1 glycoprotein. We show here that these sequences were able to specify glycolipid addition to the truncated G protein, probably after cleavage of 31 amino acids derived from Thy-1.1. The glycolipid-anchored G protein formed trimers and was expressed on the cell surface in a form that could be cleaved by phosphoinositol-specific phospholipase C. However, the rate of transport was reduced, compared with that of wild-type G protein. A second form of the G protein was generated by deletion of only the transmembrane and cytoplasmic domains. This mutant protein also formed trimers with relatively high efficiency and was secreted slowly from cells.
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PMID:Oligomerization of glycolipid-anchored and soluble forms of the vesicular stomatitis virus glycoprotein. 255 57

The inhibitory effect of the highly effective drug staurosporine on the early activation signal Ca2+ flux was investigated via multiparameter flow cytometry in human peripheral blood T lymphocytes. Staurosporine has been reported to be a specific inhibitor of protein kinase C. However, we show that it inhibits the Ca2+ influx in anti-CD3 and phytohemagglutinin-stimulated human CD4+ and CD8+ lymphocytes at concentrations between 1.0 and 10.0 ng/ml. Staurosporine decreases the number of Ca2+-positive CD4+ and CD8+ lymphocytes as well as the Ca2+ influx per cell; the drug also delays the time of the maximum response to polyclonal stimulation. In addition, we demonstrate that staurosporine affects the primary Ca2+ response via inhibition of the release of the membrane-bound Ca2+ from the endoplasmic reticulum in CD4+ and CD8+ lymphocytes. Binding studies of the anti-CD3 antibody to T lymphocytes indicate normal binding capacities in the presence of staurosporine. With respect to the classical scheme of T cell activation via phospholipase C, our data suggest that staurosporine may inhibit T cell activation primarily by its effect on the early Ca2+ flux signal.
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PMID:Complex Ca2+ flux inhibition as primary mechanism of staurosporine-induced impairment of T cell activation. 257 Jul 2

Activation of vascular smooth muscle by angiotensin II results in the phospholipase C-mediated generation of two second messengers, inositol trisphosphate (IP3) and diacylglycerol (DG). IP3 is responsible for mobilizing calcium from endoplasmic reticulum whereas DG activates protein kinase C and ultimately Na+/H+ exchange, leading to intracellular alkalinization. The IP3/calcium signal is transient, most likely serving to initiate calcium-mediated events leading to contraction, and is attenuated by activation of protein kinase C. DG formation/protein kinase C activation is sustained and may be enhanced by the concurrent intracellular alkalinization. The delay in induction of the sustained response appears to be related to cellular processing of the angiotensin II-receptor complex. Phospholipase C activity is also modulated by a cholera toxin-sensitive, pertussis toxin-insensitive guanine nucleotide regulatory protein. This guanine nucleotide regulatory protein, movement of the receptor-ligand complex, and the signals generated by the two second messengers, IP3 and DG, interact in a complex manner to cause an integrated response of vascular smooth muscle to angiotensin II stimulation.
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PMID:Angiotensin II stimulation of vascular smooth muscle cells. Secondary signalling mechanisms. 267 2

In the present study we have determinated the acetylcholinesterase molecular forms present in rat liver hepatocytes; we have also studied the association of acetylcholinesterase with the cell surface of the hepatocytes. Subcellular fractionation indicated that rough endoplasmic reticulum and plasma-membrane-enriched fractions contains G4 and G2 acetylcholinesterase forms bound to membranes. Hepatocytes incubated with phosphatidylinositol-specific phospholipase C released about 70% of the surface acetylcholinesterase. Sedimentation analysis showed that all the solubilized acetylcholinesterase activity comes exclusively from a G2 dimer. The G4 hydrophobic form of acetylcholinesterase accounts for the additional cell-surface activity. The existence of these two forms of acetylcholinesterase on the surface of hepatocytes was further established by analyzing the phosphatidylinositol-specific phospholipase C sensitivity of the acetylcholinesterase molecular forms present in isolated rat liver plasma membranes.
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PMID:Different membrane-bound forms of acetylcholinesterase are present at the cell surface of hepatocytes. 273 51

It has been reported that the incubation of isolated rat liver nuclear matrices with phospholipase C causes the digestion of the matrix-bound phospholipids and the release of most matrix-linked RNAs (Cocco et al., 1980). In this paper, the presence of phospholipids in nuclear substructures and the effects of their removal by phospholipase C digestion have been investigated by means of enzyme-colloidal gold cytochemistry. The nuclear phospholipids appear to be localized in the interchromatin areas and in the nucleolus and are virtually absent in the heterochromatin, when labelled with phospholipase C-colloidal gold. The double labelling test with ribonuclease A and phospholipase C conjugated with gold particles of different diameters shows that the nuclear phospholipids are co-localized with RNA-containing structures. The enzymatic digestion of phospholipids on thin sections of either isolated nuclei or pancreas embedded in LR White resin results in the decrease of the RNase-A colloidal gold labelling of nuclear RNA-containing structures, but not of the rough endoplasmic reticulum. The data confirm the presence of phospholipids in the nucleus in the absence of possible translocation due to isolation procedures and strengthen the hypothesis that they are involved in interactions between nucleic acids and proteins of the nuclear matrix.
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PMID:Phospholipase C digestion induces the removal of nuclear RNA: a cytochemical quantitative study. 280 84

Several aspects of the phosphoinositide signalling system recently studied in our Laboratory are considered here. 1. The formation of inositol 1:2-cyclic-4,5-trisphosphate (IcP3) and inositol 1:2-cyclic-4-bisphosphate (IcP2) have been shown here to occur in pancreatic minilobules stimulated with carbamylcholine. Identification is based on mobility on ionophoresis on paper and on HPLC, acid lability, and conversion of the inositol cyclic phosphates to their respective non-cyclic inositol phosphates on treatment with acid. The levels of inositol 1:2-cyclic phosphate (IcP), IcP2, and IcP3 were 0.7%, 6.8%, and 29.8% of their respective non-cyclic inositol phosphates. The level of IcP3 is sufficient to evoke release of calcium from the endoplasmic reticulum. 2. In a previous study, we demonstrated that on agonist stimulation of pancreatic minilobules prelabelled with [14C]arachidonate, [14C]stearate, or [3H]glycerol, there was a substantial release of all three of these compounds, amounting to approximately 50% of the total PI loss, which was up to 70% of the total cellular PI (7). It was shown that this loss in PI was due to the sequential actions of phospholipase C and diacylglycerol (DG) lipase. Evidence against the phospholipase A2 pathway was no formation of lysophosphatidylinositol. Further evidence against the phospholipase A2 pathway shown here is the lack of stimulation by agonist of glycerophosphorylinositol formation. We also show here that the stimulation of PI loss in guinea pig brain cortex slices is likely also to be via the sequential actions of phospholipase C and DG-lipase, i.e., there was an increase in the steady-state level of monoacylglycerol and a rise in free arachidonate on stimulation with acetylcholine. The formation of prostaglandin E and prostaglandin F was also increased in brain cortex, corpus striatum, and hippocampus. The effects of acetylcholine were abolished by atropine. 3. Previous studies showed that the DG-lipase inhibitor, RHC 80267, inhibited agonist-stimulated formation of glycerol and fatty acids and raised the steady-state level of DG (7). We have now used RHC 80267 as a tool to elevate the level of DG and to lower the level of arachidonate to see if either of these products might modulate the carbamylcholine-stimulated cGMP levels in pancreatic minilobules. RHC 80267 inhibited formation of cGMP. Addition of arachidonate did not affect this inhibition, nor did addition of free arachidonate to control minilobules have any effect, thus suggesting that liberation of free arachidonate by carbamylcholine was not responsible for the carbamylcholine-induced rise in cGMP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Biochemical aspects of the phosphoinositide signalling system with special reference to the formation of inositol cyclic phosphates and arachidonic acid and metabolites on agonist stimulation. 282 45

Hyperthermia causes a large (three-to fivefold) increase in intracellular free calcium ([Ca2+]i) in HA-1 fibroblasts. Increased [Ca2+]i appears initially to be due to release of Ca2+ from an internal store, probably located in the endoplasmic reticulum. A subsequent influx of Ca2+ from the extracellular medium is then observed. These heat-induced changes in Ca2+ homeostasis are correlated with turnover of the phosphoinositides (PI), a class of phospholipids whose metabolism has been shown to regulate Ca2+ in a wide variety of cells (M. J. Berridge and R. F. Irvine, Nature 312, 315 (1984]. Hyperthermia induces rapid release of inositol 1,4,5-trisphosphate (IP3) within 1 min at 45 degrees C; IP3 release precedes the heat-induced rise in [Ca2+]i. IP3 release, a result of phosphatidylinositol 4,5-bisphosphate hydrolysis by phospholipase C, is the initial step in PI turnover. Later accumulation of phosphatidic acid, another metabolite in the PI pathway, is correlated with the delayed, heat-induced influx of 45Ca2+ from the extracellular environment. The data thus indicate that heat-induced changes in Ca2+ homeostasis are correlated with activation of PI turnover. They indicate that this class of lipids may be closely involved in heat-induced changes in cellular Ca2+ homeostasis. Cell Ca2+ appears to be important in some aspects of the cellular response to heat.
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PMID:Effects of heat on cell calcium and inositol lipid metabolism. 283 58

The attachment of glycolipid anchors to the Thy-1 glycoprotein during biosynthesis was followed by the change of detergent-binding properties of biosynthetically labelled Thy-1 precursors upon phospholipase C treatment in the murine thymoma lines BW5147 and S1A. In S1A, 80% of the Thy-1 molecules were phospholipase-C-sensitive after a 2 min pulse with [35S]methionine, indicating that these molecules were already anchored via a glycolipid tail. In BW5147, 47% of the Thy-1 molecules had phospholipase-C-sensitive anchors attached after a 1.5 min labelling and, with longer pulses, this percentage rose to 76%. Tunicamycin did not block the addition of glycolipid anchors, and glycolipid attachment also occurred at 21 degrees C. The findings suggest that the attachment of glycolipid anchors occurs in the rough endoplasmic reticulum.
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PMID:Glycolipid anchors are attached to Thy-1 glycoprotein rapidly after translation. 289 53

After a 3-h incubation of Krebs II ascitic cells in the presence of phospholipase C from Clostridium welchii under nonlytic conditions, the incorporation of [3H] choline into phosphatidylcholine was increased 1.7-fold as compared to untreated cells. The total amounts of phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin were unchanged up to 3 h of incubation. The limiting step in phosphatidylcholine biosynthesis was the formation of CDP-choline catalyzed by CTP:choline-phosphate cytidylyltransferase (EC 2.7.7.15) as monitored by the decrease in phosphocholine labeling following phospholipase C treatment of cells prelabeled with [3H]choline. The specific activity of homogenate cytidylyltransferase was increased about 1.6-fold in phospholipase C-treated cells. Specific activity of the membrane fraction was increased 2-fold, whereas cytosolic specific activity decreased in phospholipase C-treated cells. The activation of cytidylyltransferase was concomitant with translocation of the enzyme from the cytosol to the membrane fraction. The latter was further fractionated using a Percoll gradient that allowed an efficient separation between endoplasmic reticulum and other subcellular membranes. In control cells, particulate cytidylyltransferase activity co-migrated with the endoplasmic reticulum and ribosome markers and not with the plasma membrane. Also, in treated cells, the stimulation of cytidylyltransferase activity occurred at the endoplasmic reticulum level and did not involve either the external cell membrane or other cellular organelles including the Golgi apparatus, lysosomes, or mitochondria. Thus, our results demonstrate that a stimulus acting on the plasma membrane promotes the translocation of the soluble form of cytidylyltransferase specifically to the endoplasmic reticulum.
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PMID:Intracellular processing of cytidylyltransferase in Krebs II cells during stimulation of phosphatidylcholine synthesis. Evidence that a plasma membrane modification promotes enzyme translocation specifically to the endoplasmic reticulum. 289 98


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