Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene for the hole-forming toxin aerolysin from Aeromonas hydrophila was sequenced. Although most of the sequence seems unrelated to that of Staphylococcus aureus alpha-toxin, both proteins are very hydrophilic, and they each contain a nearly identical string of 10 amino acids.
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PMID:Nucleotide sequence of the gene for the hole-forming toxin aerolysin of Aeromonas hydrophila. 358 74

With a view to obtaining a better understanding of the structural determinants of P1 glutamate specificity in glutamate-specific endopeptidases (GSEs), the active sites and specificity pockets of such enzymes from Bacillus licheniformis (gse-bl), Bacillus subtilis (mpr) and Staphylococcus aureus (v8 protease) were modelled. This approach was extended to the epidermolytic toxins (ETs), responsible for the staphylococcal scalded skin syndrome. We identify a canonical structure for the S1 subsite, composed of H213 and T190, both of which we predict to interact directly with the P1 glutamate. The possible importance of R30 (for gse-bl and mpr) and of the N-terminus (for gse-bl, mpr and v8 protease) was also examined. In the case of mpr, a G193C substitution is predicted to participate in a novel disulphide bridge which stabilizes C193 in such a way as to maintain the oxyanion hole. In v8, the loss or substitution of several important structural components around D102 of the catalytic triad probably explains its reduced catalytic efficiency in comparison with other GSEs. In the case of the epidermolytic toxins K216 may be important for the previously reported phospholipase C-like activity, since the model predicts that it may stabilize the negative charge on the phosphonyl group.
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PMID:Novel features of serine protease active sites and specificity pockets: sequence analysis and modelling studies of glutamate-specific endopeptidases and epidermolytic toxins. 884 31

The purpose of this study was to test the hypothesis that tyrosine phosphorylation signaling events and protein kinase C (PKC) activation mediate vascular endothelial growth factor-A(165) (VEGF)-induced endothelial cell (EC) proliferation and barrier dysfunction in bovine pulmonary artery EC monolayers. A size-selective permeability assay showed that VEGF stimulated a delayed, prolonged (6-45 h), concentration-dependent (50-200 ng/ml, approximately 1-4 nM) increase in the number of predominantly small-"pore" transport pathways (<60 A) across EC monolayers. The tyrosine kinase inhibitor herbimycin A (HA) and the selective PKC inhibitor bisindolylmaleimide (BIM) prevented this phenomenon. After 6-24 h, VEGF-treated monolayers displayed an HA- and BIM-sensitive reorganization of beta-catenin adherens junctions with fingerlike projections and the loss of beta-catenin at sites of small paracellular hole formation. HA and BIM prevented the VEGF-induced increase in EC growth. HA blocked the VEGF-induced rapid and prolonged (10 min-45 h) increases in the phosphotyrosine (PY) contents of VEGF receptor 2, phospholipase C-gamma1, paxillin, and beta-catenin as well as approximately 140- and 128- to 117-kDa proteins, whereas BIM inhibited only the tyrosine phosphorylation of beta-catenin. These data suggest that VEGF initiates increased EC growth and chronic, small-pore endothelial barrier dysfunction by PY signaling through beta-catenin that depends on PKC.
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PMID:VEGF stimulates tyrosine phosphorylation of beta-catenin and small-pore endothelial barrier dysfunction. 1056 61

The isolated rotor cylinder of the ATP synthase from Ilyobacter tartaricus was reconstituted into two-dimensional crystalline arrays. Atomic force microscopy imaging indicated a central cavity on one side of the rotor and a central plug protruding from the other side. Upon incubation with phospholipase C, the plug disappeared, but the appearance of the surrounding c subunit oligomer was not affected. This indicates that the plug consists of phospholipids. As the detergent-purified c cylinder is completely devoid of phospholipids, these are incorporated into the central hole from one side of the cylinder during the reconstitution procedure.
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PMID:The central plug in the reconstituted undecameric c cylinder of a bacterial ATP synthase consists of phospholipids. 1157 27

The cellular events involved in muscarinic analgesia were investigated in the mouse hot-plate test. Intracerebroventricular (i.c.v.) pretreatment with antisense oligonucleotides (aODNs) against the alpha subunit of G(q) and G(11) proteins prevented the analgesia induced by physostigmine and oxotremorine. Furthermore, administration of the phospholipase C (PLC) inhibitor U-73122, as well as the injection of an aODN complementary to the sequence of PLCbeta(1), antagonized the increase of the pain threshold induced by both cholinomimetic drugs. In mice undergoing treatment with LiCl, which impairs phosphatidylinositol synthesis, or treatment with heparin, an IP(3) receptor antagonist, the antinociception induced by physostigmine and oxotremorine was dose-dependently antagonized. I.c.v. pretreatment with TMB-8, a blocker of Ca(2+) release from intracellular stores, prevented the increase of pain threshold induced by the investigated cholinomimetic drugs. Coadministration of Ca(2+) restored the muscarinic analgesia in LiCl, heparin, and TMB-8-preatreated mice. On the other hand, i.c.v. pretreatment with the selective protein kinase C (PKC) inhibitor calphostin C, resulted in a dose-dependent enhancement of physostigmine- and oxotremorine-induced antinociception. The administration of PKC activators, such as PMA and PDBu, dose dependently prevented the cholinomimetic drug-induced increase of pain threshold. Neither aODNs nor pharmacological treatments employed produced any behavioral impairment of mice as revealed by the rota-rod and hole-board tests. These results indicate a role for the PLC-IP(3) pathway in central muscarinic analgesia in mice. Furthermore, activation of PKC by cholinomimetic drugs may represent a pathway of negative modulation of muscarinic antinociception.
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PMID:The phospholipase C-IP3 pathway is involved in muscarinic antinociception. 1273 33

The cellular events involved in acetyl-L-carnitine (ALCAR) analgesia were investigated in the mouse hot plate test. I.c.v. pretreatment with aODNs against the alpha subunit of G(q) and G(11) proteins prevented the analgesia induced by ALCAR (100 mg kg(-1) s.c. twice daily for 7 days). Administration of the phospholipase C (PLC) inhibitors U-73122 and neomycin, as well as the injection of an aODN complementary to the sequence of PLCbeta(1), antagonized the increase of the pain threshold induced by ALCAR. Pretreatment with U-73343, an analogue of U-73112 inactive on PLC, did not modify ALCAR analgesic effect. In mice undergoing treatment with LiCl, which impairs phosphatidylinositol synthesis, or pretreatment with TMB-8, a blocker of Ca(++) release from intracellular stores, the antinociception induced by ALCAR was dose-dependently antagonized. I.c.v. treatment with heparin, an IP(3) receptor antagonist, prevented the increase of pain threshold induced by the investigated compound, analgesia that was restored by co-administration of D-myo-inositol. On the other hand, i.c.v. pretreatment with the selective protein kinase C (PKC) inhibitors calphostin C and cheleritryne, resulted in a dose-dependent potentiation of ALCAR antinociception. The administration of PKC activators, such as PMA and PDBu, dose-dependently prevented the ALCAR-induced increase of pain threshold. Neither aODNs nor pharmacological treatments produced any behavioral impairment of mice as revealed by the rota-rod and hole board tests. These results indicate that central ALCAR analgesia in mice requires the activation of the PLC-IP(3) pathway. By contrast, the simultaneous activation of PKC may represent a pathway of negative modulation of ALCAR antinociception.
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PMID:Acetyl-L-carnitine requires phospholipase C-IP3 pathway activation to induce antinociception. 1522 7

The supraspinal cellular events involved in H(1)-mediated hyperalgesia were investigated in a condition of acute thermal pain by means of the mouse hot-plate test. I.c.v. administration of the phospholipase C (PLC) inhibitors U-73122 and neomycin antagonized the hyperalgesia induced by the selective H(1) agonist FMPH. By contrast, U-73343, an analogue of U-73122 used as negative control, was unable to modify the reduction of the pain threshold induced by FMPH. In mice undergoing treatment with LiCl, which impairs phosphatidylinositol synthesis, or treatment with heparin, an IP(3)-receptor antagonist, the hyperalgesia induced by the H(1)-receptor agonist remained unchanged. Similarly, pretreatment with D-myo inositol did not alter the H(1)-induced hypernociceptive response. Neither i.c.v. pretreatment with TMB-8, a blocker of Ca(2+) release from intracellular stores, nor pretreatment with thapsigargin, a depletor of Ca(2+) intracellular stores, prevented the decrease of pain threshold induced by FMPH. On the other hand, i.c.v. pretreatment with the selective protein kinase C (PKC) inhibitors calphostin C and chelerytrine resulted in a dose-dependent prevention of the H(1)-receptor agonist-induced hyperalgesia. The administration of PKC activators, such as PMA and PDBu, did not produce any effect on FMPH effect. The pharmacological treatments employed did not produce any behavioral impairment of mice as revealed by the rota-rod and hole-board tests. These results indicate a role for the PLC-PKC pathway in central H(1)-induced hyperalgesia in mice. Furthermore, activation of PLC-IP(3) did not appear to play a major role in the modulation of pain perception by H(1)-receptor agonists.
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PMID:H1-receptor stimulation induces hyperalgesia through activation of the phospholipase C-PKC pathway. 1522 8