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

---

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

The recent identification of the nociceptin receptor-nociceptin system and the description of its role in nociceptive processing has produced numerous investigative studies. A fundamental part of this research is to understand the cellular signaling events (i.e. the building blocks) upon which the pharmacology of this intriguing system is based. As anticipated, nociceptin receptor activation inhibits the formation of cAMP formation via a pertussis toxin-sensitive G-protein. This indicates that nociceptin receptor couples to the G(i)/G(o) class of G-protein(s). However, there is now growing evidence for nociceptin activation of additional signaling pathways, including MAP kinase and phospholipase C/[Ca(2+)](i). These signaling events are discussed in this review.
...
PMID:Cellular actions of nociceptin: transduction mechanisms. 1099 29

The effect of alpha-NeuAc(2-->6)Gal/GalNAc-specific lectin from Sambucus nigra (SNA) on the release of lysozyme from human neutrophils was studied in vitro. Interaction of cells with the lectin was accompanied by dose-dependent release of lysozyme, which was increased in the presence of cytochalasin B. The involvement of intracellular signaling pathways in the lectin-induced degranulation of neutrophils was determined using a panel of specific inhibitors tested at concentrations in the range of 10-100 microM. Aristolochic acid (a phospholipase A2 inhibitor), indomethacin (a cyclooxygenase inhibitor), neomycin sulfate (a phospholipase C inhibitor), trifluoperazine (a calmodulin antagonist/protein kinase C inhibitor), N-ethylmaleimide (a sulfhydryl reagent), and guanosine-5;-O-(2-thiodiphosphate) (a G-protein inhibitor) were found to reduce SNA-induced lysozyme release from neutrophils by 20-45%. The treatment of cells with bisindolylmaleimide (a protein kinase C inhibitor), H-8 (an inhibitor of protein kinases A, C, G and of myosin light chain kinase), PD 98059 (a MAP kinase inhibitor), and (+/-)-methoxyverapamil (a Ca2+-channel blocker) failed to affect the release of lysozyme. These results indicate that only selective intracellular pathways associated with activation of G-proteins and phospholipid metabolism as well as the thiol-dependent signaling systems are apparently involved in the realization of the SNA-induced degranulation response of human neutrophils.
...
PMID:Effect of signaling inhibitors on the release of lysozyme from human neutrophils activated by Sambucus nigra agglutinin. 1100 87

This study was conducted to examine the mechanism(s) of synergistic interaction of histamine- and adrenaline-mediated human platelet aggregation. We found that platelet aggregation mediated by subthreshold concentrations of histamine (1-4 microm) plus adrenaline (0.5-2 microm) is inhibited by both an alpha(2)-adrenoceptor blocker (yohimbine) and a histamine (H1) receptor antagonist (diphenhydramine). In examining the role of the downstream signalling pathway, we found that such an interaction is inhibited by the calcium channel blockers verapamil and diltiazem. However, platelet aggregation by adrenaline plus histamine was inhibited by very low concentrations of the phospholipase C (PLC) inhibitor, U73122 (IC(50)= 1.2 microm), the MEK inhibitor, PD98059 (IC(50)= 1.1 microm) and the cyclo-oxygenase (COX) inhibitor, indomethacin (IC(50)= 7 microm). However the inhibition of receptor tyrosine kinase, protein kinase C and phosphatidylinositol 3-kinase by genistien, chelerythrine and wortmannin, respectively, had no significant effect on aggregation. Similarly the nitric oxide donor (SNAP) had no effect on this synergism. These data suggest that the synergistic effect of histamine and adrenaline during human platelet aggregation is receptor mediated and involves activation of PLC, COX and MAP kinase signalling pathways.
...
PMID:Synergistic interaction of adrenaline and histamine in human platelet aggregation is mediated through activation of phospholipase, map kinase and cyclo-oxygenase pathways. 1102 12

Tumour necrosis factor-alpha (TNFalpha) has been reported to induce potent growth inhibition of committed myeloid progenitor cells, whereas it is a potential growth stimulator of human CD34(+)CD38(-) multipotent haematopoietic cells. The present study was aimed at evaluating the respective role of two phospholipases, phosphatidylcholine-specific phospholipase C (PC-PLC) and phospholipase D (PLD) in the response of the CD34(+) CD38(-) KG1a cells to TNFalpha. In these cells TNFalpha triggered phosphoinositide 3-kinase (PI3K)-dependent PC hydrolysis within 4-8 min with concomitant production of both diacylglycerol (DAG) and phosphocholine (P-chol). DAG and P-chol production was accompanied by extracellular-signal-related protein kinase-1 ('ERK-1') activation and DNA-synthesis stimulation. PC-PLC stimulation was followed by PI3K-independent PLD activation with concomitant phosphatidic acid (PA) production followed by PA-derived DAG accumulation and sustained nuclear factor kappaB (NF-kappaB) activation. PLD/NF-kappaB signalling activation played no role in the TNFalpha proliferative effect and conferred no consistent protection of KG1a cells towards antileukaemic agents. Altogether these results suggest that, in KG1a cells, TNFalpha can stimulate in parallel PC-PLC and PLD, whose lipid products activate in turn mitogen-activated protein kinase (MAP kinase) and NF-kappaB signalling respectively. Finally, our study suggests that PC-PLC, but not PLD, plays a role in the TNFalpha proliferative effect in immature myeloid cells.
...
PMID:Phosphatidylcholine-specific phospholipase C and phospholipase D are respectively implicated in mitogen-activated protein kinase and nuclear factor kappaB activation in tumour-necrosis-factor-alpha-treated immature acute-myeloid-leukaemia cells. 1102 32

We previously reported that sphingosine 1-phosphate (S-1-P), a sphingomyelin metabolite, activates p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase in aortic smooth-muscle A10 cells. In the present study, we investigated the effect of sphingomyelin metabolites on phospholipase C-catalyzing phosphoinositide hydrolysis induced by arginine vasopressin (AVP) in A10 cells. C(2)-ceramide and sphingosine had little effect on inositol phosphate (IP) formation stimulated by AVP. S-1-P, which alone slightly stimulated the IPs formation, dose-dependently amplified the AVP-induced formation of IPs. Tumor necrosis factor-alpha enhanced the AVP-induced formation of IPs. However, S-1-P did not enhance the formation of IPs by NaF, a heterotrimeric GTP-binding protein activator. Pertussis toxin inhibited the effect of S-1-P. PD98059, an inhibitor of the upstream kinase that activates p44/p42 MAP kinase, had little effect on the enhancement by S-1-P. SB203580, an inhibitor of p38 MAP kinase, suppressed the effect of S-1-P on the formation of IPs by AVP. SB203580 inhibited the AVP-induced phosphorylation of p38 MAP kinase. Pertussis toxin suppressed the phosphorylation of p38 MAP kinase by S-1-P. These results indicate that S-1-P amplifies AVP-induced phosphoinositide hydrolysis by phospholipase C through p38 MAP kinase in vascular smooth-muscle cells.
...
PMID:Enhancement by sphingosine 1-phosphate in vasopressin-induced phosphoinositide hydrolysis in aortic smooth-muscle cells: involvement of p38 MAP kinase. 1102 53

Using NIH 3T3 cells, we have investigated nuclear phosphoinositide metabolism in response to insulin, a molecule which acts as a proliferating factor for this cell line and which is known as a powerful activator of the mitogen-activated protein (MAP) kinase pathway. Insulin stimulated inositol lipid metabolism in the nucleus, as demonstrated by measurement of the diacylglycerol mass produced in vivo and by in vitro nuclear phosphoinositide-specific phospholipase C (PI-PLC) activity assay. Despite the fact that nuclei of NIH 3T3 cells contained all of the four isozymes of the beta family of PI-PLC (i.e. beta1, beta2, beta3, and beta4), insulin only activated the beta1 isoform. Insulin also induced nuclear translocation of MAP kinase, as demonstrated by Western blotting analysis, enzyme activity assays, and immunofluorescence staining, and this translocation was blocked by the specific MAP kinase kinase inhibitor PD98059. By means of both a monoclonal antibody recognizing phosphoserine and in vivo labeling with [(32)P]orthophosphate, we ascertained that nuclear PI-PLC-beta1 (and in particular the b subtype) was phosphorylated on serine residues in response to insulin. Both phosphorylation and activation of nuclear PI-PLC-beta1 were substantially reduced by PD98059. Our results conclusively demonstrate that activation of nuclear PI-PLC-beta1 strictly depends on its phosphorylation which is mediated through the MAP kinase pathway.
...
PMID:Insulin selectively stimulates nuclear phosphoinositide-specific phospholipase C (PI-PLC) beta1 activity through a mitogen-activated protein (MAP) kinase-dependent serine phosphorylation. 1111 9

Signaling mechanisms underlying neurotrophic regulation of synaptic transmission are not fully understood. Here we show that neurotrophin-3 (NT3)-induced potentiation of synaptic transmission at the neuromuscular synapses is blocked by inhibition of phosphoinositide-3 kinase, phospholipase C-gamma or the downstream IP3 receptors of phospholipase C-gamma, but not by inhibition of MAP kinase. However, neither stimulation of Ca2+ release from intracellular stores by photolysis of caged IP3, nor expression of a constitutively active phosphoinositide-3 kinase (PI3K*) in presynaptic motoneurons alone is sufficient to enhance transmission. Photo-uncaging of IP3 in neurons expressing PI3K* elicits a marked synaptic potentiation, mimicking the NT3 effect. These results reveal an involvement of PI3 kinase in transmitter release, and suggest that concomitant activation of PI3 kinase and IP3 receptors is both necessary and sufficient to mediate the NT3-induced synaptic potentiation.
...
PMID:PI-3 kinase and IP3 are both necessary and sufficient to mediate NT3-induced synaptic potentiation. 1113 33

Fertilization is accompanied by a rapid and transient calcium release in eggs, which is required for the onset of zygotic developmental program or 'egg activation'. Recently, it was found that Src family tyrosine kinase (SFK)-dependent phospholipase C (PLC) activity is necessary for the calcium transience in fertilized Xenopus eggs. The present study demonstrates that hydrogen peroxide (H2O2) stimulates protein-tyrosine phosphorylation in Xenopus eggs, which occurs primarily in the egg cortex of the animal hemisphere as revealed by indirect immunofluorescence study. Egg SFK was found to be upregulated by H2O2 while the SFK-specific inhibitor PP1 effectively blocked H2O2-induced tyrosine phosphorylation. As in fertilized eggs, PLCgamma, but not Shc, was tyrosine-phosphorylated in H2O2-treated eggs. H2O2 also caused inositol 1,4,5-trisphosphate (IP3) production and sustained calcium release. After limited application of H2O2, elevated SFK activity and tyrosine phosphorylation were quickly reversed. Under such conditions, eggs showed cortical contraction and dephosphorylation of p42 MAP kinase, both of which are indicative of egg activation. These egg activation events, as well as H2O2-induced IP3 production and calcium release, were sensitive to PP1 and PLC inhibitor U-73122. Together, the present study demonstrated that H2O2 can mimic, at least in part, early events of Xenopus egg activation that require an SFK-dependent PLC pathway.
...
PMID:Hydrogen peroxide induces Src family tyrosine kinase-dependent activation of Xenopus eggs. 1114 52

PGF2alpha triggers the demise of the corpus luteum whereby progesterone synthesis is inhibited, the luteal structure regresses, and the estrus cycle resumes. Upon binding to its heterotrimeric G-protein-coupled receptors, PGF2alpha initiates the phospholipase C/diacylglycerol and inositol-1,4,5-trisphosphate/Ca(2+)-protein kinase C (PKC) signaling pathway. More recently, we have demonstrated that PGF2alpha activates extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase signaling through a Raf-dependent mechanism in bovine luteal cells. However, the relationship between PKC and ERK activation in PGF2alpha signaling has not been clearly defined. Moreover, the signaling pathway that PGF2alpha uses to regulate gene expression is unknown. In this report, primary cultures of bovine luteal cells were used to address the role of PKC in ERK activation and the signaling pathway for induction of c-fos and c-jun messenger RNA (mRNA) expression in response to PGF2alpha. By using a PKC inhibitor and a PKC-deficient luteal cell model, we observed that phorbol ester-responsive isoforms of PKC were required for ERK phosphorylation and activation by PGF2alpha (1 microM) or phorbol 12-myristate 13-acetate (PMA) (20 nM). In PGF2alpha- and PMA-treated cells, active ERK MAP kinase was localized in the nucleus. PGF2alpha-induced ERK phosphorylation was dose-dependently inhibited by the MEK1 inhibitor PD098059 (1-50 microM). The expression of c-fos and c-jun mRNA in luteal cells was markedly increased by treatment with PGF2alpha (1 microM) or PMA (20 nM) for 30 min. We also observed that activation of ERK MAP kinase was required for the expression of c-fos and c-jun mRNA in response to PGF2alpha and PMA because it was abrogated by blocking the ERK pathway with PD098059. In addition, PGF2alpha and PMA-induced c-fos and c-jun mRNA expression was abolished in the PKC-deficient cells. Taken together, our data demonstrate that a PKC-dependent ERK MAP kinase pathway mediates the expression of c-fos and c-jun mRNA in PGF2alpha-treated bovine luteal cells.
...
PMID:Induction of c-fos and c-jun messenger ribonucleic acid expression by prostaglandin F2alpha is mediated by a protein kinase C-dependent extracellular signal-regulated kinase mitogen-activated protein kinase pathway in bovine luteal cells. 1115 62

The Ca2+ rise at fertilization of echinoderm eggs is initiated by a process requiring the sequential activation of a Src family kinase, phospholipase C gamma, and the inositol trisphosphate receptor/channel in the endoplasmic reticulum. The consequences of the Ca2+ rise include exocytosis of cortical granules, which establishes a block to polyspermy, and inactivation of MAP kinase, which functions in linking the Ca2+ rise to the reinitiation of the cell cycle.
...
PMID:Ca2+ signalling during fertilization of echinoderm eggs. 1116 46


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---