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)

Phosphoinositide-specific phospholipase C (PLC) activity of human platelet membranes was activated by the nonhydrolyzable guanine nucleotide GTP gamma S. This activation did not occur in either membranes prepared from dibutyryl cyclic AMP-pretreated platelets (A-membranes) or those prepared from untreated cells and subsequently incubated with cyclic AMP (cAMP) (B-membranes). This cAMP-mediated inhibition was abolished in the presence of inhibitors of cAMP-dependent protein kinase (A-kinase), suggesting that the inhibition was due to phosphorylation of (a) protein component(s). No significant differences were observed in the basal PLC activity and the extent of pertussis toxin-catalyzed ADP-ribosylation among control membranes and the two types of phosphorylated membranes (A- and B-membranes). GTP-binding activities of Gs, Gi and GTP-binding proteins of lower molecular masses were not altered by the phosphorylation of the membranes. These findings suggest that a GTP-binding protein is involved in the GTP gamma S-mediated activation of PLC and that cAMP (plus A-kinase) inhibits this activation by phosphorylating a membrane protein (probably a 240-kDa protein), rather than the GTP-binding protein or PLC itself. It is likely that this phosphorylation uncouples the GTP-binding protein from PLC.
...
PMID:Inhibition by cyclic AMP of guanine nucleotide-induced activation of phosphoinositide-specific phospholipase C in human platelets. 253 21

Norepinephrine (NE) stimulated FRTL-5 thyroid cells via an alpha 1-adrenergic receptor, resulting in cytosolic Ca2+ [( Ca2+]i) mobilization and activation of phospholipase C. Adenosine and its receptor agonist, phenylisopropyladenosine (PIA), although not exerting a direct effect, markedly enhanced the NE-induced changes. Basal NE action was not totally abolished whereas the permissive action of adenosine and PIA was completely abolished by pretreatment of the cells with islet-activating protein (IAP), pertussis toxin. The decrease in cAMP level induced by adenosine or PIA is not the cause of their permissive effect, since the effect was not reversed by the addition of cAMP-increasing agents. We conclude that an IAP substrate GTP-binding protein(s) plays a novel role in forming a stimulatory coupling between an adenosine receptor and an alpha 1-adrenergic receptor-coupled phospholipase C system.
...
PMID:Stimulation of adenosine receptor enhances alpha 1-adrenergic receptor-mediated activation of phospholipase C and Ca2+ mobilization in a pertussis toxin-sensitive manner in FRTL-5 thyroid cells. 254 83

The regulation of soluble phosphoinositide-specific phospholipase C from adult human epidermis by guanine nucleotide was investigated. In the presence of physiologic concentrations of Ca++ (1 microM) and Mg++ (1.5 mM), neither phosphatidylinositol (PI) nor phosphatidylinositol-4,5-bisphosphate (PIP2) were appreciably hydrolyzed. Addition of guanosine-5'-triphosphate (GTP) or guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S) significantly stimulated hydrolysis of PIP2, but not PI. Stimulation of PIP2 hydrolysis by GTP was dose-dependent between 1-100 microM GTP. Other nucleoside triphosphates and nucleotide analogues were unable to substitute for GTP or GTP-gamma-S. A GTP-gamma-S-stimulated PIP2 hydrolysis was inhibited by guanosine-5'-O-(2-thiodiphosphate (GDP-beta-S). The phospholipase C preparation specifically bound [35S]GTP-gamma-S and this binding was also inhibited by GDP-beta-S. In addition to a 41,000-dalton pertussis toxin substrate, the phospholipase C preparation contained 3-4 GTP binding proteins with molecular weights between 20,000-30,000. These data demonstrate that human epidermis contains a soluble GTP-dependent phospholipase C activity that specifically hydrolyzes PIP2 and suggest that this reaction is regulated by a GTP-binding protein(s).
...
PMID:GTP-dependent hydrolysis of phosphatidylinositol-4,5-bisphosphate by soluble phospholipase C from adult human epidermis. 254 16

Polymorphonuclear leukocytes (PMNL) release superoxide anions formed by a membrane-bound NADPH oxidase induced by stimulations. Properties of the inducers and their antagonists indicate that Ca2+, GTP-binding protein (G-protein), phospholipase C and Ca2+, phospholipid-dependent protein kinase (C-kinase) are mainly associated with the stimulation of receptors. Low concentrations of ATP induce the oxidase accompanied by the increase in the intracellular Ca2+ due to the flux from the medium and the storage site. ATP-gamma-S, UTP and ITP are effective but mononucleotides, dinucleotides, GTP and CTP are not. Leukotriene B4 (LTB4) which acts as a chemotactic agent and the inducer of the NADPH oxidase is catabolized. It is hydroxylated by a specific cytochrome P450 and then oxidized to a carboxy derivative by a cytosolic alcohol dehydrogenase and a microsomal aldehyde dehydrogenase in PMNL. Active NADPH oxidase was obtained by incubating membrane and cytosolic components of resting PMNL in the presence of sodium dodecyl sulfate (SDS). Two cytosolic components were obtained by an affinity chromatography on 2',5'-ADP Sepharose. One component is active in the presence of GTP or GTP-gamma-S and the other component in the presence of another cytosolic fraction.
...
PMID:Metabolism of stimulated polymorphonuclear leukocytes. 254 77

The mechanism of Ca2+ influx stimulated by arginine vasopressin (AVP) was studied in cultured rat smooth muscle cells. AVP stimulated 45Ca2+ influx even in the presence of nifedipine, a Ca2+ antagonist that inhibits voltage-dependent Ca2+ channel. NaF, a GTP-binding protein activator, mimicked the AVP-stimulated 45Ca2+ influx. The 45Ca2+ influx stimulated by a combination of AVP and NaF was not additive. The affinity of AVP receptor was decreased by guanosine 5'-O-(3-thiotriphosphate). Pertussis toxin failed to affect the AVP-stimulated 45Ca2+ influx. AVP did not stimulate cAMP production, but increased inositol trisphosphate generation. Both AVP-stimulated 45Ca2+ influx and inositol trisphosphate generation were inhibited by neomycin, a phospholipase C inhibitor, in a dose-dependent manner, and the patterns of both inhibitions were similar. These results suggest that, in rat smooth muscle cells, AVP-stimulated Ca2+ influx is mediated exclusively through phosphoinositide hydrolysis.
...
PMID:Ca2+ influx stimulated by vasopressin is mediated by phosphoinositide hydrolysis in rat smooth muscle cells. 254 69

A part of the GTP gamma S-binding activity in murine thymocyte membranes was found to have affinity to a concanavalin A (Con A)-Sepharose column. The material was identified as Gi (inhibitory GTP-binding protein) on the basis of the molecular weight and by islet activating protein-dependent ADP-ribosylation and anti-alpha i (alpha subunit of Gi) immunoblotting. However, when the membranes prepared from Con A-stimulated thymocytes were used, no GTP gamma S-binding activity was detected in the Con A-bound fraction, suggesting that Gi physically and specifically associated with Con A acceptors dissociates upon Con A stimulation. Furthermore, another GTP gamma S-binding protein (25 kDa), which is quite similar to a novel phosphoinositide-specific phospholipase C (PI-PLC)-associated G protein in calf thymocytes (Wang, P., Toyoshima, S., & Osawa, T. (1988) J. Biochem. 103, 137-142), was detected among the Con A-Sepharose-bound proteins with the chemical cross-linking technique. When the 40 kDa and 25 kDa G proteins associated with Con A receptor(s) were isolated and their direct effects on the activity of partially purified PI-PLC as to phosphatidylinositol 4,5-bisphosphate hydrolysis were examined, the 25 kDa G protein was found to enhance the PI-PLC activity more effectively. On the other hand, pretreatment of cells with islet-activating protein completely abolished the inhibitory effect of Con A on the prostaglandin E1 and isoproterenol-induced increases of cellular cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Concanavalin A receptor(s) possibly interacts with at least two kinds of GTP-binding proteins in murine thymocytes. 254 73

Various adenine nucleotides activated phospholipase C of FRTL-5 cell membranes in the following order of activity, ATP gamma S greater than ATP greater than AppNp greater than AppCp = ADP greater than MeSATP. This order was well consistent with that observed in intact cells. Such activation occurred only in the presence of appropriate concentrations of GTP gamma S and Ca2+, in a way similar to the norepinephrine-induced activation. NaF, a non-specific GTP-binding protein (G-protein) activator, also stimulated the enzyme. These adenine nucleotides, norepinephrine and NaF-induced activations were inhibited by GDP beta S. We conclude that a G-protein is involved in the adenine nucleotides-induced activation of phospholipase C via P2-purinergic receptor in FRTL-5 cells.
...
PMID:P2-purinergic agonists activate phospholipase C in a guanine nucleotide- and Ca2+-dependent manner in FRTL-5 thyroid cell membranes. 254 54

Vasopressin V1 receptors were solubilized from rat liver plasma membranes with the detergent lysophosphatidylcholine. [[3H]Arginine]vasopressin (AVP) binding to the solubilized preparations was specific and saturable, with a dissociation constant of 0.6 nM. Cross-linking of [125I]vasopressin to the solubilized fraction, studied by SDS/polyacrylamide-gel-electrophoretic analysis, demonstrated the presence of a 65 kDa band which was specifically labelled with [125I]vasopressin. Specific binding of [3H]AVP to these solubilized receptors was decreased by guanine nucleotides, but not by adenosine 5'-[beta gamma-imido]triphosphate. Addition of vasopressin increased specific binding of 35S-labelled guanosine 5'-[gamma-thio]triphosphate (GTP[35S]) to the solubilized fractions, indicating co-solubilization of GTP-binding protein(s) [G-protein(s)] and vasopressin receptors. The solubilized fraction was insensitive to both cholera- and pertussistoxin treatment. Immunoblotting of the solubilized fraction with antibodies specific for a phosphoinositide-specific phospholipase C (PI-PLC I) demonstrated the presence of a 60 kDa protein. Anti-PI-PLC I antiserum immunoprecipitated solubilized vasopressin-binding sites from rat liver (V1), but not solubilized vasopressin-binding sites from hog kidney (V2). Similar results were obtained with an anti-PI-PLC I IgG affinity column. The solubilized (V1) receptors were enriched by ion-exchange and high-performance gel-filtration liquid chromatography. Vasopressin-binding activity was co-eluted with PI-PLC I and GTP[S]-binding activity on a DEAE-Sepharose column. The major vasopressin- and GTP[35S]-binding activities were co-eluted with PI-PLC I activity at approx. 240 kDa suggesting that vasopressin receptors from rat liver membranes can be solubilized as a complex of receptor-coupler-effector by using the detergent lysophosphatidycholine.
...
PMID:Solubilization of rat liver vasopressin receptors as a complex with a guanine-nucleotide-binding protein and phosphoinositide-specific phospholipase C. 254 66

The action of carbamoylcholine (Cchol), NaF and other agonists on the generation of inositol phosphates (IPs) was studied in dog thyroid slices prelabelled with myo-[2-3H]inositol. The stimulation by Cchol (0.1 microM-0.1 mM) of IPs accumulation through activation of a muscarinic receptor [Graff, Mockel, Laurent, Erneux & Dumont (1987) FEBS Lett. 210, 204-210] was pertussis- and cholera-toxin insensitive. Ins(1,4,5)P3, Ins(1,3,4)P3 and InsP4 were generated. NaF (5-20 mM) also increased IPs generation (Graff et al., 1987); this effect was potentiated by AlCl3 (10 microM) and unaffected by pertussis toxin. Although phorbol dibutyrate (5 microM) abolished the cholinergic stimulation of IPs generation (Graff et al., 1987), it did not affect the fluoride-induced response. Cchol and NaF did not require extracellular Ca2+ to exert their effect, and neither KCl-induced membrane depolarization nor ionophore A23187 (10 microM) had any influence on basal IPs levels, or on cholinergic stimulation. However, more stringent Ca2+ depletion with EGTA (0.1 or 1 mM) decreased basal IPs levels as well as the amplitude of the stimulation by Cchol without abolishing it. Dibutyryl cyclic AMP, forskolin, cholera toxin and prostaglandin E1 had no effect on basal IPs levels and did not decrease the response to Cchol. Iodide (4 or 40 microM) also strongly decreased the cholinergic action on IPs, this inhibition being relieved by methimazole (1 mM). Our data suggest that Cchol activates a phospholipase C hydrolysing PtdIns(4,5)P2 in the dog thyroid cell in a cyclic AMP-independent manner. This activation requires no extracellular Ca2+ and depends on a GTP-binding protein insensitive to both cholera toxin and requires no extracellular Ca2+ and depends on a GTP-binding protein insensitive to both cholera toxin and pertussis toxin. The data are consistent with a rapid metabolism of Ins(1,4,5)P3 to Ins(1,3,4)P3 via the Ins(1,4,5)P3 3-kinase pathway, followed by dephosphorylation by a 5-phosphomonoesterase. Indeed, a Ca2+-sensitive InsP3 3-kinase activity was demonstrated in tissue homogenate. Stimulation of protein kinase C and an organified form of iodine inhibit the Cchol-induced IPs generation. The negative feedback of activated protein kinase C could be exerted at the level of the receptor or of the receptor-G-protein interaction.
...
PMID:Stimulation of generation of inositol phosphates by carbamoylcholine and its inhibition by phorbol esters and iodide in dog thyroid cells. 255 11

The role of guanine nucleotides in catecholamine secretion was investigated in alpha-toxin-permeabilized chromaffin cells. The stable GTP analogues, GTP-gamma-S (guanosine 5'-(gamma-thio)triphosphate) and GMP-PNP (guanosine 5'-(beta,gamma-imido)triphosphate), potentiated calcium-evoked catecholamine release in a dose-dependent manner. This effect was reversed by GDP-beta-S (guanosine 5'-(beta-thio)diphosphate) indicating that a GTP-binding protein plays a modulatory role in the calcium-dependent secretory process in chromaffin cells. Calcium and the phosphorylating nucleotide ATP were both necessary for secretion, even in the presence of GTP analogues, suggesting that the activation of a GTP-regulatory protein alone does not trigger exocytosis in these cells. TPA (12-O-tetradecanoylphorbol-13-acetate), a direct activator of protein kinase C, was found to mimic the effects of the GTP analogues, inducing a dose-dependent potentiation of the calcium-evoked release in alpha-toxin-permeabilized cells. Treatment of the permeabilized cells with sphingosine, a potent inhibitor of protein kinase C, completely abolished the stimulatory effects of both TPA and GTP-gamma-S. Moreover, long term incubation of chromaffin cells with TPA, a treatment which depletes cells of protein kinase C activity, suppressed the stimulatory effects of GTP-gamma-S. Protein kinase C is activated when it becomes membrane-bound in the presence of calcium and diacylglycerol; here, GTP-gamma-S was found to enhance the calcium-induced translocation of protein kinase C to membranes in alpha-toxin-permeabilized cells. These results suggest that guanine nucleotides modulate secretion by activating protein kinase C-linked events in chromaffin cells. Furthermore, the potentiation of calcium-induced secretion in alpha-toxin-permeabilized cells following activation of protein kinase C either directly with TPA or indirectly with GTP analogues provides additional support for the concept that protein kinase C may exert a positive control directly on the intracellular exocytotic machinery.
...
PMID:A reassessment of guanine nucleotide effects on catecholamine secretion from permeabilized adrenal chromaffin cells. 267 32


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

---