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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gonadotropin (GTH) release in static incubations of dispersed goldfish pituitary cells was stimulated by chicken GTH-releasing hormone II (cGnRH-II), salmon (s)GnRH, phospholipase A2, phospholipase C, phospholipase D, and arachidonic acid (AA). Coincubations with nordihydroguaiaretic acid (NDGA), 5,8,11,14-eicosatetraenoic acid, and indomethacin did not alter the GTH responses to cGnRH-II. In contrast, NDGA reduced sGnRH-stimulated GTH release. Incubation with Ca(2+)-deficient medium abolished the GTH responses to cGnRH-II, reduced sGnRH-stimulated GTH release, but did not alter AA actions on GTH secretion. Apomorphine, a dopamine agonists that had been shown to partially inhibit the GTH responses to sGnRH and to abolish those induced by cGnRH-II, did not affect the hormone response to AA. However, the partial inhibitory actions of NDGA and apomorphine on sGnRH-induced GTH release were additive. These findings suggest the existence of a major difference in cGnRH-II and sGnRH stimulation of GTH release--AA metabolism is not involved in cGnRH-II, as opposed to sGnRH actions. This difference in second messenger activation may also explain the differential sensitivity of the two GnRH peptides to dopamine inhibition and manipulations of extracellular Ca2+ availability. The results further suggest that dopamine and AA affect GTH release via non-overlapping signal transduction pathways.
Mol Cell Endocrinol 1991 Aug
PMID:Lack of involvement of arachidonic acid metabolism in chicken gonadotropin-releasing hormone II (cGnRH-II) stimulation of gonadotropin secretion in dispersed pituitary cells of goldfish, Carassius auratus. Identification of a major difference in salmon GnRH and chicken GnRH-II mechanisms of action. 193 48

Metabolic radiolabeling of adult worms of Schistosoma mansoni with [3H]myristic acid has revealed that the fatty acid is incorporated into more than 15 proteins. We have shown that two of these proteins, a 200-kDa glycoprotein known to be exposed on the surface of the adult worm following praziquantel treatment and a 22-kDa glycoprotein that shows an enhanced immune reactivity with sera of vaccinated mice, are anchored to the adult worm membrane via a glycosylphosphatidylinositol (GPI) linkage. Both antigens partitioned preferentially into the detergent phase of Triton X-114 and were susceptible, following immunoaffinity purification, to hydrolysis by phosphatidylinositol-specific phospholipase C (PIPLC) from Bacillus thuringiensis and phospholipase C from Bacillus cereus. Diacylglycerol (DAG) was released following hydrolysis by bacterial PIPLC; however, Trypanosoma brucei GPIPLC failed to release the diacylglycerol from either protein. Treatment with nitrous acid generated phosphatidylinositol (PI) from both proteins, and phospholipase D from rat serum cleaved phosphatidic acid from the 200-kDa protein. Although the functional significance of these GPI-anchored proteins is unknown, their release from the surface of the schistosome may contribute to immune evasion.
Mol Biochem Parasitol 1990 Jan 15
PMID:Identification and characterization of glycosylphosphatidylinositol-linked Schistosoma mansoni adult worm immunogens. 213 72

The hydrolysis of the minor cell membrane lipid phosphatidylinositol-4,5-bisphosphate mediates the action of many growth factors and hormones. As an approach to the development of specific inhibitors of this process, we have synthesized a series of analogs of myo-inositol and have evaluated their ability to serve as substrates for phosphatidylinositol synthetase. Modification at the 2-, 3-, or 4-positions produced compounds unable to serve as substrates, but several 5-modified analogs retained activity as substrates of phosphatidylinositol synthetase. The product formed from 5-deoxy-5-fluoro-myo-[3H]inositol by phatidylinositol synthetase was hydrolyzed by phospholipase D and gave 5-deoxy-5-fluoro-myo-inositol as the radiolabeled product. Two analogs, 5-deoxy-myo-inositol and 5-deoxy-5-fluoro-myo-inositol, were shown to permeate L1210 leukemia cells and be incorporated into cellular phospholipid. Analysis of the radiolabeled lipids formed on incubation of L1210 cells with 5-deoxy-5-fluoro-myo-[3H]inositol indicated that the fradulent lipid formed was further phosphorylated to the monophosphate but not to the diphosphate form.
Mol Pharmacol 1988 Jun
PMID:Substrate properties of analogs of myo-inositol. 283 38

We examined the effect of phospholipase D (PLD) treatment on the ability of Trypanosoma cruzi to interact with phagocytic and nonphagocytic host cells. The presence of PLD during the incubation of parasites with mouse peritoneal macrophages caused significant increases in both the number of parasites per 100 macrophages and the percentage of macrophages associated with parasites. Parasites pretreated with PLD, washed, and then incubated with untreated macrophages showed a marked increase in parasite-host cell association. In contrast, when only the macrophages were pretreated with PLD, there was no significant change in the association. Parasites required 45 min of PLD treatment before a significant enhancement in parasite-host cell association was observed. The action of PLD could be blocked by the presence of a competitive substrate, phosphatidylethanolamine, during enzyme treatment. The enhancing effect of PLD treatment of the parasites was relatively long lasting since it was still seen 3 h after the enzyme had been removed. The enhancing effect of PLD probably reflected an increased capacity of T. cruzi to associate with host cells rather than increased phagocytosis of PLD-altered parasites by macrophages since similar results were obtained when rat heart myoblasts, which are not phagocytic, were used as host cells. Neither the presence of phospholipids or PLD phospholipid cleavage products during the incubation of T. cruzi with macrophages had any effect on parasite-host cell association. These results show that PLD-mediated alterations to parasite phospholipids increase parasite-host cell association, and suggest that these phospholipids play a role in the initial stages of host cell infection by T. cruzi.
Mol Biochem Parasitol 1985 Nov
PMID:Increased host cell-Trypanosoma cruzi interaction following phospholipase D treatment of the parasite surface. 390 93

The 125I-labeled S-100 specific binding to a Triton X-100 (TX-100) extract of synaptosomal particulate fractions (SYN) was investigated. The results indicate that (a) S-100 binding to the TX-100 extract is partially irreversible after a critical association time at 37 degrees C, while it is fully reversible after any association time at 4 degrees C; (b) trypsin and phospholipase C partially reverse the S-100 binding, while phospholipase D enhances the interaction to some extent, in a dose-dependent way; (c) EDTA and high concentrations of NaCl or KCl are more efficient as inhibitors of the S-100 binding to the TX-100 extract than as 125I-labeled S-100 dissociating agents, in analogy with previous observations with SYN; and (d) two main populations of solubilized S-100 binding sites can be evidenced by gel filtration and sucrose gradient centrifugation when low amounts of the TX-100 extract are processed and/or low S-100 concentrations are used, while two additional molecular species are separated when greater amounts of either factors are tested. These results suggest the possibility that S-100 may be involved in the regulation of some membrane activities.
Cell Mol Neurobiol 1983 Sep
PMID:Biochemical and physicochemical properties of the solubilized S-100 protein binding activity of synaptosomal particulate fractions. 667 Dec 2

In dibutyryl-cAMP-differentiated HL-60 cells, histamine H1 and formyl peptide receptors mediate increases in the cytosolic Ca2+ concentration ([Ca2+]i) via pertussis toxin-sensitive G proteins of the Gi family. We compared the effects of 2-(3-chlorophenyl)-histamine (CPH) [2-[2-(3-chlorophenyl)-1H-imidazol-4-yl] ethanamine], one of the most potent and selective H1 receptor agonists presently available, with those of histamine and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) in these cells. CPH increased [Ca2+]i through Ca2+ mobilization and Ca2+ influx. Unlike histamine-induced rises in [Ca2+]i, those induced by CPH were not desensitized in a homologous manner, and there was no cross-desensitization between CPH and histamine. Like fMLP, CPH activated phospholipases C and D, tyrosine phosphorylation, superoxide anion formation, and azurophilic granule release. The effects of CPH on [Ca2+]i, phospholipase D, and superoxide anion formation were inhibited by pertussis toxin. CPH and fMLP stimulated high affinity GTP hydrolysis by Gi proteins in HL-60 membranes. They also enhanced binding of guanosine-5'-O-(3-thio)triphosphate and GTP azidoanilide to, and cholera toxin-catalyzed ADP-ribosylation of, Gi protein alpha subunits. Histamine receptor antagonists did not inhibit the stimulatory effects of CPH, and CPH did not reduce fMLP binding in HL-60 membranes. Our data suggest that CPH activates Gi proteins in HL-60 cells through a receptor agonist-like mechanism that is, however, independent of known histamine receptor subtypes and formyl peptide receptors. CPH may be an agonist at an as yet unknown histamine receptor subtype or, by analogy with other cationic-amphiphilic substances, may activate G proteins directly. Future studies will have to take into consideration the fact that CPH, in addition to activating H1 receptors, may show other, most unexpected, stimulatory effects on G protein-mediated signal transduction processes.
Mol Pharmacol 1994 Apr
PMID:The H1 receptor agonist 2-(3-chlorophenyl)histamine activates Gi proteins in HL-60 cells through a mechanism that is independent of known histamine receptor subtypes. 751 61

Protein tyrosine kinases (PTKs) of the src family are thought to play an important role in platelet signal transduction, but little is known about the targets of these enzymes in platelets. We determined that exposure of human platelets to pervanadate, an inhibitor of protein tyrosine phosphatases, caused an increase in the activity of phospholipase D (PLD), an enzyme that might be involved in signaling events leading to aggregation or secretion. To further investigate whether tyrosine phosphorylation is a step in the pathway of activation of PLD in response to thrombin, we tested the effects of a series of PTK inhibitors on the activity of platelet PLD. PLD was activated in response to 0.3 U/ml thrombin, and this activation was reduced by several of the PTK inhibitors, especially genistein, methyl 2,5-dihydroxycinnamate (MDHC), ST271, and the tyrphostins A25 and A47. In saponin-permeabilized platelets, we observed a marked inhibition of GTP-gamma S-stimulated PLD by many of the PTK inhibitors, consistent with the possibility that PTKs are involved in the regulation of PLD activity by a G-protein or small GTP-binding protein. MDHC did not affect PLD activity in permeabilized cells, which suggests that this compound might inhibit PLD in intact platelets via another pathway. The inhibitors were also tested for their effects on the phosphorylation of a peptide substrate of src-family PTKs in a platelet membrane preparation and in permeabilized platelets. Several of the compounds partially inhibited peptide phosphorylation in the membrane preparation and in permeabilized platelets, most notably ST271, ST638, and tyrphostin A25.(ABSTRACT TRUNCATED AT 250 WORDS)
Cell Mol Biol (Noisy-le-grand) 1994 Jul
PMID:Inhibition of phospholipase D of human platelets by protein tyrosine kinase inhibitors. 752 16

Stimulation of phospholipase D activity is frequently observed during agonist activation of Ca(2+)-mobilizing receptors, but the cellular functions of this signaling pathway are not well defined. Pituitary gonadotrophs express Ca(2+)-mobilizing receptors for gonadotropin-releasing hormone (GnRH) and endothelin (ET), activation of which stimulates luteinizing hormone secretion and transient expression of c-fos. In pituitary cells and alpha T3-1 gonadotrophs, GnRH action was associated with both initial and sustained diacylglycerol (DG) production, whereas ET-1 induced only a transient DG response. Also, phospholipase D activity, estimated by the production of phosphatidylethanol from phosphatidylcholine in the presence of ethanol, was stimulated by GnRH but not ET-1. Such formation of phosphatidylethanol at the expense of phosphatidic acid (PA) during GnRH-induced activation of phospholipase D significantly reduced the production of PA, DG, and cytidine diphosphate diacylglycerol. Inhibition of PA-phosphohydrolase activity by propranolol also decreased GnRH-induced DG production and, in contrast to ethanol, increased PA and cytidine diphosphate diacylglycerol levels. The fall in DG production caused by ethanol and propranolol was accompanied by inhibition of GnRH-induced c-fos expression, whereas agonist-induced luteinizing hormone release was not affected. In contrast to their inhibitory actions on GnRH-induced early gene expression, neither ethanol nor propranolol affected ET-1-induced c-fos expression, or GnRH- and ET-1-induced inositol trisphosphate/Ca2+ signaling. These findings demonstrate that phospholipase D participates in stimulus-transcription but not stimulus-secretion coupling, and indicate that DG is the primary signal for this action.
Mol Biol Cell 1995 Aug
PMID:Dependence of stimulus-transcription coupling on phospholipase D in agonist-stimulated pituitary cells. 757 6

The contributions of phosphoinositide (PI)- and phosphatidylcholine (PC)-specific phospholipases [PI-specific phospholipase C (PI-PLC), PC-specific phospholipase C (PC-PLC), and phospholipase D (PLD)] to diacylglycerol (DAG) formation and regulation of the enzymes by G proteins, Ca2+, and protein kinase C (PKC) were examined in dispersed intestinal circular and longitudinal muscle cells. DAG formation induced by cholecystokinin was biphasic and paralleled by PKC activity. The initial phase (approximately 1 min) was mediated by PI-PLC in circular muscle cells and by both PI- and PC-PLC in longitudinal muscle cells, whereas the sustained phase was mediated by PC-PLC and PLD in both cell types. PC-PLC activity during the initial phase was identified by rapid formation of the initial products [3H]phosphocholine (5 sec) and [3H]myristate-labeled DAG (approximately 15 sec). PLD activity did not contribute to DAG formation during the initial phase, and PI hydrolysis had no effect on PC-PLC or PLD activity during the initial or sustained phases. PLD activity during the sustained phase was evident by the formation of [3H]phosphatidylethanol, a PLD-specific transphosphatidylation product. Dephosphorylation of phosphatidic acid (PA) by phosphatidate phosphohydrolase (PPH) accounted for about 50% of DAG formation; inhibition of PPH activity by propranolol or suppression of PA formation by ethanol inhibited DAG formation by 59-69% and 57-62%, respectively. Residual DAG in the presence of ethanol was augmented 55-57% by DAG kinase inhibitor, whereas residual PA was inhibited by 60-67%, implying that PA was derived from DAG, and DAG from PLC-mediated PC hydrolysis. In the presence of ethanol, calphostin C inhibited phosphatidylethanol formation but had no effect on PA or DAG levels, implying that only PLD activity was modulated by PKC. Maintenance of resting intracellular Ca2+ concentrations, rather than an agonist-induced increase in the intracellular Ca2+ concentration, was required for optimal PC-PLC and PLD activity. Guanosine-5'-O-(beta-thio)diphosphate abolished DAG and PA formation in reversibly permeabilized muscle cells. We conclude that DAG formation in intestinal muscle is mediated by time-dependent activation of three phospholipases (PI-PLC, PC-PLC, and PLD) and two converting enzymes (DAG kinase and PPH). PC-PLC and PLD are Ca2+ dependent and appear to be G protein coupled; only PLD is PKC sensitive.
Mol Pharmacol 1995 Aug
PMID:Agonist-mediated activation of phosphatidylcholine-specific phospholipase C and D in intestinal smooth muscle. 765 63

We have characterized a membrane-bound phosphatidylcholine (PC) specific phospholipase C (PC-PLC) in plasma membranes from rat cardiac muscle, and have investigated the role of PC-PLC and PC-specific phospholipase D (PC-PLD) activities in the mechanism of action of atrial natriuretic factor (ANF). In purified sarcolemma, ANF stimulated over a wide range of concentrations with a maximum at 10(-11) M the hydrolysis of phosphatidylcholine through PC-PLD giving phosphatidate and choline, whereas higher concentrations of ANF (10(-10) M) preferentially stimulated PC breakdown through PC-PLC to form diacylglycerol and phosphocholine. To confirm the involvement of the PC-PLD in the mechanism of ANF action, we measured the transphosphatidylation reaction, a specific assay for this phospholipase which in the presence of ethanol catalyses the phosphatidylethanol formation from PC. ANF stimulated phosphatidylethanol formation with the same dose-response behavior as phosphatidate formation. The significant diacylglycerol increase at 10(-10) M ANF, in the presence of propranolol, a potent inhibitor of phosphatidate phosphatase which can hydrolyse phosphatidate to give diacylglycerol, suggested a direct involvement of PC-PLC. The use of GTP-gamma-S, a non hydrolysable analog of GTP, and of pertussis toxin showed the involvement of a pertussis toxin insensitive G protein in PC-PLC mediated ANF signal transduction. We suggest a differential effect of ANF on PC breakdown by phospholipases C and D depending on the concentration of the peptide.
J Mol Cell Cardiol 1994 Dec
PMID:Selective activation by atrial natriuretic factor of phosphatidylcholine-specific phospholipase activities in purified heart muscle plasma membranes. 773 Oct 62


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