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

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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)

The effect of phospholipases and proteases on the membrane-bound and solubilized A1 adenosine receptor has been studied. Phospholipids modulate the [3H]N6-(R)-phenylisopropyladenosine binding to A1 adenosine receptors in crude membranes and in soluble preparations, because changes in the phospholipid environment decrease both the binding capacity and the affinity for the ligand. It has become clear that 1) there is co-solubilization of receptor and phospholipids; 2) the phospholipid requirements are different for the coupled and the uncoupled receptor; 3) a net charge in the polar head produced by phospholipase D prevents the agonist binding to the receptor-G protein complex; alternatively, when the whole polar head is removed by phospholipase C the uncoupled receptor is altered; and 4) the protease action upon the receptor suggests that receptor coupled to G protein is more protected by the membrane than the uncoupled receptor. In kinetic experiments performed on membranes it was demonstrated that phospholipase C and trypsin increased the Kd value of the high-affinity state by modifying both k1 and k-1. In contrast they only modified the dissociation constant of the low-affinity state. In conclusion it should be noted that phospholipids play a key role for the binding of R-PIA to A1 adenosine receptor. Also, a different disposition within the membrane of the coupled and uncoupled receptor is encountered.
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PMID:Effect of phospholipases and proteases on the [3H]N6-(R)-phenylisopropyladenosine ([3H]R-PIA) binding to A1 adenosine receptors from pig cerebral cortex. 179 Nov 89

Investigations have been carried out on the lipid dependence of membrane-bound phosphatidylinositol-specific phospholipase C in rat liver plasma membranes. For this purpose the phospholipid composition of rat liver plasma membranes has been modified in two different ways. The first method included enrichment of plasma membranes with different phospholipids in the presence of lipid transfer proteins, and the second a partial delipidation by means of exogenous phospholipases A2 and C and selective enrichment with different phospholipids. The results indicated that almost all used phospholipids induced activation of phosphatidylinositol-specific phospholipase C except sphingomyelin. Phosphatidylethanolamine and egg yolk phosphatidylcholine were observed to be most effective in phospholipase C activation.
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PMID:Phospholipid dependence of phospholipase C in rat liver plasma membranes. 179 53

Earlier studies have shown that bradykinin stimulated release of catecholamines from chromaffin cells by an influx of calcium through dihydropyridine-insensitive channels, and also that bradykinin stimulated (poly)phosphoinositide hydrolysis. To investigate membrane-bound second messengers in chromaffin cells, and to elucidate any role these may play in stimulus-secretion coupling, we have studied the influence of bradykinin on diacylglycerol and phosphatidic acid (PA). Using equilibrium labelling of primary cultures of chromaffin cells with [3H]arachidonic acid or [3H]glycerol, we found no influence of bradykinin (10 nM) on labelled diacylglycerol formation, either in the presence or absence of inhibitors of diacylglycerol lipase or kinase. However, when we used cells prelabelled with 32Pi for 2.5 h, we found that bradykinin produced a substantial stimulation of label found in PA, with an EC50 value of about 1 nM. This bradykinin stimulation of [32P]PA formation was only partially dependent on extracellular calcium, in contrast to the smaller response to nicotine, which was completely dependent on extracellular calcium. Short (10 min) pretreatment with tetradecanoylphorbol acetate (TPA) almost completely eliminated the bradykinin-stimulated formation of inositol phosphates, but failed to affect bradykinin stimulation of label in PA, suggesting that PA production in response to bradykinin is not downstream of phospholipase C activation. TPA alone failed to stimulate [32P]PA substantially, whereas long-term (24 or 48 h) treatment with TPA failed to attenuate the response to bradykinin. Diacylglycerol kinase inhibitors were also without effect on the bradykinin stimulation of [32P]PA. These results suggest that bradykinin stimulates PA production by a mechanism independent of the activation of protein kinase C.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of bradykinin on diacylglycerol and phosphatidic acid accumulation in cultured bovine adrenal chromaffin cells. 186 Nov 47

CD14, expressed on the surface of monocytes as a phospholipid-linked protein, is a receptor for serum LPS binding protein/LPS complex. It was specifically down-modulated after stimulation of monocytes by physiologic activating/differentiating agents such as bacterial LPS and IFN-gamma, by the pharmacologic agents PMA and calcium ionophore A23187, and by anti-CD14 antibodies. The down-modulation was almost totally blocked at 4 degrees C or at pH 4.5 and markedly inhibited by the protease inhibitors diisopropylfluorophosphate and PMSF. A soluble labeled CD14 was isolated from culture supernatant of surface iodinated monocytes after their activation, indicating that CD14 is shed from the cell surface rather than internalized. The size of the soluble CD14 shed from the monocytes in vitro was smaller than that of either the membrane-bound form or a soluble CD14 cleaved from the cell surface by phosphatidyl inositol-specific phospholipase C, but identical to the size of one of the two major soluble CD14 forms normally found in human serum. These data suggest that CD14 shedding induced by monocyte stimulation may play an important role in the regulation of surface CD14 expression.
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PMID:Shedding as a mechanism of down-modulation of CD14 on stimulated human monocytes. 188 Apr 16

Histamine H2 receptor (H2R) has been shown to be coupled to adenylate cyclase. However, we have previously demonstrated that H2R-specific stimulation also activated phospholipase C in human HL-60 promyelocytic leukemia cells (Mitsuhashi M. et al. J. Biol. Chem. 264:18356, 1989). We have extended these studies on HL-60 cells to investigate whether histamine-bovine serum albumin conjugates (HA-BSA) specifically recognize H2R and activate phospholipase C pathways. Both histamine (HA) and HA-BSA increased intracellular concentrations of calcium in a H2R specific manner. However, HA-induced calcium mobilization was transient and returned to the basal level within 1-2 min, whereas HA-BSA-induced calcium mobilization was sustained for more than 10 min as a result of the additional influx of extracellular calcium. More interestingly, fluorescein (FITC) labeled HA-BSA was less incorporated into cytosols and present in the membrane fractions for more than 60 min, whereas membrane-bound FITC-HA was rapidly incorporated into cytosols. Furthermore, the levels of inositol 1,3,4,5-tetrakisphosphate, which is known to activate calcium channels were more sustained after HA-BSA stimulation than those of HA alone. These data suggest that H2R activation mechanism is more complex and may be modified by this slowly metabolized "compound ligand".
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PMID:Multiple signaling pathways of histamine H2 receptors. 190 5

NADPH oxidase is a superoxide-generating, membrane-bound complex activated in stimulated phagocytes or in a reconstituted system consisting of membranes, cytosolic components and arachidonate or SDS. To delineate mechanism of oxidase activation in the cell-free system, hydrolysis of phosphoinositides in the combined membrane-cytosol oxidase mixture was investigated. Arachidonate promoted hydrolysis of membrane-[3H]-phosphatidylinositol by cytosolic phospholipase C. PI hydrolysis was similarly supported by other unsaturated fatty acids and by SDS. Unlike activation of the NADPH oxidase, PI hydrolysis required the presence of calcium ions. Implications of these findings to the mechanism of NADPH oxidase activation are discussed.
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PMID:Arachidonate supports hydrolysis of phosphatidylinositol by neutrophil cytosolic phospholipase C: relation to NADPH oxidase. 190 42

Murine T cells synthesize and express a cell-surface glycophospholipid anchored 40 kDa and a secreted water-soluble 39 kDa Qa-2 polypeptide. We have examined the biosynthetic pathways which lead to the production of the membrane-bound and water-soluble isoforms of the Qa-2 molecule. Using the detergent TX-114, both detergent (membrane)-bound and soluble Qa-2 polypeptides can be identified in cell lysates and can be distinguished by charge and molecular weight. Two membrane-bound forms, a 40-kDa Endo H resistant cell-surface form and a 38 kDa-Endo H sensitive form can be identified, both of which can be biosynthetically labeled with 3H-ethanolamine and can be converted to water soluble forms by digestion with a phosphatidylinositol specific phospholipase C. In addition, several water soluble polypeptides at 39, 37, 35 kDa, and a minor species at 33 kDa were identified, none of which radiolabel with 3H-ethanolamine. While the 39-kDa polypeptide was Endo H resistant, the other isoforms were sensitive to Endo H digestion. Pulse chase experiments and molecular weights of the deglycosylated core polypeptides suggest a precursor to product relationship between the intracellular water-soluble species and the mature 39-kDa secreted Qa-2 molecule. This relationship is supported by the observation that murine L cells transfected with the Qa-2 encoding class I gene Q7 fail to express membrane-bound Qa-2 molecules yet synthesize both intracellular water-soluble and secreted Qa-2 molecules. These findings argue for a pathway in which secreted soluble Qa-2 molecules are derived from intracellular precursors.
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PMID:Biosynthesis of glycophospholipid bound and secreted murine class I Qa-2 polypeptides. 196 Dec 2

The alpha 1-adrenergic receptor exists as at least two distinct subtypes, alpha 1a and alpha 1b. Based on hydrophobic exclusion studies and limited proteolysis of the cloned receptor, it appears to possess characteristics analogous to other membrane-bound receptors including seven membrane spanning domains, three extracellular, and three intracellular loops, with extensive glycosylation near the extracellular amino terminus. Although the receptor is coupled to phospholipase C in cardiac myocytes, with activation resulting in the production of inositol trisphosphate (IP3) and diacylglycerol, recent findings suggest that the receptor may also be linked to phospholipase A2, phospholipase D, and cyclic nucleotide phosphodiesterase. The alpha 1-adrenergic receptor has been shown to increase in response to myocardial ischemia in a number of different species and to mediate not only positive inotropic effects, but also to contribute substantially to arrhythmogenesis. The increase in alpha 1-adrenergic receptors can also occur in isolated adult ventricular myocytes in response to hypoxia, a mechanism which appears to be secondary to the sarcolemmal accumulation of long-chain acylcarnitines. This increase in alpha 1-adrenergic receptors in hypoxic myocytes is also linked to an enhanced increase in IP3 in response to receptor stimulation. These and other findings obtained in vivo during ischemia suggest that alpha 1-adrenergic mechanisms can become prominent in myocardium under pathophysiologic conditions in which a depressed contractile state exists and may therefore serve as a secondary inotropic system. However, the arrhythmogenic effects of stimulation of the alpha 1-adrenergic receptor in the ischemic heart in man may contribute substantially to arrhythmogenesis and, thereby, to the incidence of sudden cardiac death.
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PMID:Modulation of alpha-adrenergic receptors and their intracellular coupling in the ischemic heart. 196 2

We report the quantification of a membrane-bound phospholipase C in human epidermis which is active against the physiologically relevant substrate, phosphatidylinositol 4,5-bisphosphate. The level of this enzyme is significantly increased in the psoriatic lesion, both on a weight and protein basis. Etiological implications of this observation are discussed.
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PMID:Membrane-bound phospholipase C activity in normal and psoriatic epidermis. 196 75

G proteins are membrane-bound molecules involved in coupling of surface receptors with signal transduction effector systems in multiple cell types including T lymphocytes. Given that mature T cells which lack antigen receptors (CDl-Ti) are refractory to stimulation through CD2 or other accessory molecules, T cell receptor components likely play a critical role in coupling surface receptors with signal transduction effectors. It has recently been proposed that modulation of T cell receptor components with MAbs results in a physical loss or functional inactivation of G protein(s). In view of the importance of the T cell activation process, we herein examined G proteins in untreated or antibody-modulated Jurkat T cells as well as in genetic variants lacking either CD3-Ti or CD2 surface receptors. 43- and 41-kDa G protein alpha chains are ADP ribosylated with cholera (CTX) and pertussis (PTX) toxins, respectively, in wild type and receptor minus cell populations. In the wild type Jurkat cell line as well as in CD3- and CD2- variants, AlF4- can activate the G protein(s) presumably associated with phospholipase C to generate polyphosphoinositide turnover as well as an increase in cytoplasmic free calcium ions. Furthermore, G protein(s) linked to adenylylcyclase, a pathway which inhibits T lymphocyte activation, can be directly activated with CTX in the absence of CD3-Ti or CD2 on the membrane. Importantly, AlF4- can also induce polyphosphoinositide turnover in Jurkat cells whose T cell receptor proteins have been modulated with anti-CD3 MAb. These data provide functional and biochemical evidence that at least certain G proteins are intact in the absence of surface expression of CD3-Ti or CD2 molecules and imply that CD3-Ti desensitization is not singularly due to G protein loss.
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PMID:Characterization of functional GTP binding proteins in Jurkat T cell mutants lacking either CD3-Ti or CD2 surface receptors. 197 60


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