Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inositol phosphate responses to substance P, bombesin, cholecystokinin, and the muscarinic cholinergic agonist methacholine were examined in the rat pancreatoma cell line AR4-2J. It was found that each agonist produced a distinct temporal pattern of inositol phosphate formation. Furthermore, these different response patterns resulted, at least in part, from different patterns of homologous receptor desensitization. The response to substance P desensitized rapidly and completely within 90 sec. After a 10-15-min refractory period, the response recovered with a t1/2 of approximately 1 hr. The response to methacholine also completely desensitized. However, in this case desensitization developed slowly over the course of 40 min, and no recovery of responsiveness was detected for up to 45 min after the cessation of stimulation. The inositol phosphate responses to bombesin and cholecystokinin were similar to one another and appeared to be composed of two phases. Initially, there was a robust activation of phospholipase C. This initial phase was followed within 20 sec by a second phase of lesser magnitude. For bombesin, attenuation of the initial phase was due to rapid, but only partial, desensitization of the response. Furthermore, the concentration of bombesin required to maintain the second phase of the response was about 100-fold lower than that required to maximally activate the initial phase of the response. These results may indicate multiple mechanisms for the regulation of different phospholipase C-linked receptors in this cell line.
Mol Pharmacol 1991 Nov
PMID:Different modes of regulation for receptors activating phospholipase C in the rat pancreatoma cell line AR4-2J. 171 68

Cells expressing mutant epidermal growth factor (EGF) receptors have been used to study mechanisms through which EGF increases phospholipase C (PLC) activity. C-terminal truncation mutant EGF receptors are markedly impaired in their ability to increase inositol phosphate formation compared with wild-type EGF receptors. Mutation of the single tyrosine self-phosphorylation site at residue 992 to phenylalanine in an EGF receptor truncated at residue 1000 abolished the ability of EGF to increase inositol phosphate formation. C-terminal deletion mutant receptors that are impaired in their ability to increase inositol phosphate formation effectively phosphorylate PLC-gamma at the same tyrosine residues as do wild-type EGF receptors. EGF enhances PLC-gamma association with wild-type EGF receptors but not with mutant receptors lacking sites of tyrosine phosphorylation. These results indicate that formation of a complex between self-phosphorylated EGF receptors and PLC-gamma is necessary for enzyme activation in vivo. We propose that both binding of PLC-gamma to activated EGF receptors and tyrosine phosphorylation of the enzyme are necessary to elicit biological responses. Kinase-active EGF receptors lacking sites of tyrosine phosphorylation are unable to signal increased inositol phosphate formation and increases in cytosolic Ca2+ concentration.
Mol Cell Biol 1992 Jan
PMID:A site of tyrosine phosphorylation in the C terminus of the epidermal growth factor receptor is required to activate phospholipase C. 172 95

The role of membrane phospholipids in porcine testicular androgen and 16-androstene biosynthesis was examined by monitoring the effects of phospholipase treatments on the activities of the steroid transforming enzymes. Untreated (control) microsomes from immature pig testes converted pregnenolone to 17-hydroxypregnenolone and DHA to 5,16-androstadien-3 beta-ol (andien-beta) and 4,16-androstadien-3-one (dienone) in the 16-androstene pathway, these metabolites accounting for most (65%) of the pregnenolone converted. The 4-ene steroids in the androgen pathway (progesterone, 17-hydroxyprogesterone, androstenedione and testosterone) totalled less than 10% of the pregnenolone metabolites. No estrogens or 5 alpha-reduced metabolites were detected. Treatment with phospholipase A2 or C, decreased the conversion of pregnenolone to 4-ene-3-oxo steroids but did not decrease the quantities of 5-ene-3 beta-hydroxysteroids. Confirmation of these findings was obtained by measuring the individual enzymatic steps. Phospholipases A2 and C significantly reduced the conversion of DHA to androstenedione and andien-beta to dienone but did not affect 17-hydroxylase or 'andien-beta-synthetase'. However, when the C-17, 20 lyase step was measured alone, phospholipase C decreased the quantity of androstenedione produced indicating that the side-chain cleavage reaction may involve a lipid component. The different effects of phospholipases on these enzymes suggests that pregnenolone metabolism may be regulated by alterations in the membrane microenvironment.
J Steroid Biochem Mol Biol 1992 Jan
PMID:Phospholipases modulate immature pig testicular androgen and 16-androstene biosynthetic pathways in vitro. 173 40

The simple method is proposed for isolation and purification of staphylococcal alpha-toxin that permits one to obtain the homogeneous toxic protein with high activity. The time necessary for maximal toxin production at cultivation has been defined. The thermostability and interferonogenic characteristics of the obtained alpha-toxin were studied.
Mol Gen Mikrobiol Virusol 1991 Sep
PMID:[A simple method of purifying staphylococcal alpha-toxin and a study of its properties]. 174 73

Quantitatively, the major phospholipid in the muscle of the nematode Ascaris suum was found to be phosphatidylcholine (lecithin). Stimulation of Ascaris muscle with acetylcholine or the agonists carbachol and levamisole increased the level of phosphorylcholine, 1,2-diacylglycerides and phosphatidic acid. Increased levels of these compounds, together with the demonstration of phospholipase C activity, suggest that phospholipid hydrolysis may be associated with the ACh response of the muscle via second messenger pathways. In other tissues, diacylglycerides and phosphatidic acid have been reported to regulate protein kinase C activity. Protein kinase C activity also was demonstrated in the muscle of Ascaris. For optimal activity the kinase was dependent upon Ca2+, unsaturated 1,2-diacylglyceride and phospholipid. All of the data are in accord with the possible involvement of a second messenger system being operative in the ACh-stimulated contraction of Ascaris muscle.
Mol Biochem Parasitol 1991 Oct
PMID:Phospholipids and protein kinase C in acetylcholine-dependent signal transduction in Ascaris suum. 176 27

Although stimulated [3H] inositol phosphate turnover has been demonstrated in isolated, perfused [3H] inositol prelabelled rat hearts, there is still no information regarding Ins (1,4,5)P3 levels in intact cardiac muscle. Using a D-myo-Ins(1,4,5)P3 assay system, Ins(1,4,5)P3 levels were determined in isolated perfused rats hearts during ischaemia, reperfusion and alpha 1-adrenergic stimulation via noradrenaline (3 x 10(-5) M). Control hearts contained +/- 674 pmols Ins(1,4,5)P3/g dry heart weight. Myocardial Ins(1,4,5)P3 levels were significantly decreased (+/- 389 pmols/g dry heart weight) after exposure to 20 mins of normothermic ischaemic cardiac arrest (NICA). Reperfusion produced a marked increase in Ins(1,4,5,)P3 levels (+/- 1,115 pmols/g dry heart weight) after only 30 s. Noradrenaline caused a 3-4 fold increase in tissue Ins(1,4,5)P3 levels within 30 s. After 20 mins stimulation with noradrenaline, the Ins(1,4,5)P3 levels were still significantly elevated. The rise in tissue Ins(1,4,5)P3 levels during reperfusion as well as during noradrenaline administration was counteracted by neomycin (0.5 x 10(-3) M), an inhibitor of phosphoinositidase specific phospholipase C. In both events neomycin restored the Ins(1,4,5)P3 levels to control values. For correlation of tissue Ins(1,4,5)P3 levels with mechanical events, noradrenaline (3 x 10(-5) M), in the presence of 10 mM LiCl, 10(-7) M propranolol and 10(-7) M atropine, was administered to isolated perfused rat hearts and the mechanical performance recorded over a period of 20 mins. Noradrenaline caused a significant increase in peak systolic pressure and work performance which was maintained for at least 10 mins, suggesting that the positive inotropic effects of noradrenaline may be provoked by Ins(1,4,5)P3. Furthermore, the finding that 20 min NICA followed by 30 s reperfusion causes an immediate significant increase in Ins(1,4,5)P3 content suggests a role for the phosphatidylinositol pathway in the intracellular Ca2+ overloading, characteristic of ischaemia-reperfusion.
J Mol Cell Cardiol 1991 Jul
PMID:Increased myocardial inositol trisphosphate levels during alpha 1-adrenergic stimulation and reperfusion of ischaemic rat heart. 179 34

Staphylococcus aureus alpha-toxin was treated with trypsin, which inactivates the toxin. Two-dimensional crystals of the modified protein were produced on preformed lipid layers. The projection structure obtained by electron crystallographic analysis of a large number of crystals showed tetragonal p4 symmetry and a resolution of approximately 12 A. The fragments of the toxin, 17 and 18 kDa large, were arranged in a way resembling those observed earlier for the native protein (Olofsson et al., J. Mol. Biol. 214, 299-306, 1990). However, after trypsin treatment the stain-deficient region corresponding to one alpha-toxin monomer shows two separated subdomains of similar size. This separation is probably related to the inability of the modified toxin to undergo the conformational change thought to be essential for the membrane-damaging effect.
 ...
PMID:The structure of Staphylococcus aureus alpha-toxin: effects of trypsin treatment. 180 78

To investigate the effects of guanine nucleotide-binding regulatory proteins (G proteins) on hormonal regulation of prolactin (PRL) synthesis and secretion, the qualitative distribution of G protein alpha-subunits and their mRNAs was studied in three functionally different pituitary tumour cell lines (GH cells) and normal rat pituitary tissue. Levels of basal and modulated adenylyl cyclase (AC) and phospholipase C (PLC) activities are also included. GH cells and pituitary tissue contained various amounts of mRNAs and protein for Gs alpha, Gi-2 alpha, Gi-3 alpha and Go alpha, while mRNA for Gi-1 alpha was only detected in normal pituitary tissue. Gz alpha/Gx alpha mRNA was expressed in all pituitary cell lines as well as in pituitary tissue. Go alpha mRNA and Gz alpha/G x alpha mRNA displayed size heterogeneity. These findings may have importance in the understanding of hormone regulation of second messenger systems.
Mol Cell Endocrinol 1991 Apr
PMID:Cell specific distribution of guanine nucleotide-binding regulatory proteins in rat pituitary tumour cell lines. 182 Sep 76

Although many cells anchor surface proteins via moieties that are sensitive to phosphatidylinositol-specific phospholipase C (PI-PLC), the anchor moieties of surface proteins of mouse L929 cells resist PI-PLC. By constructing stable hybrids between L929 and lymphoma cells that express glycolipid-anchored proteins in a PI-PLC-sensitive form, we show that PI-PLC resistance behaves as a recessive trait. Since putative mannolipid precursors of the lipid anchors bear alkali-labile substituents which make them resist PI-PLC, these observations are most simply interpreted by postulating that L929 lacks a critical anchor deacylase. Unlike the L929 cell line, two of its descendants, the LM cell line and its thymidine kinase-negative variant (LM-TK-), do not express glycolipid-anchored proteins on their surface. Moreover, unlike L929 cells, LM-TK- cells rapidly inactivate at least one lipid-anchored enzyme in a compartment sensitive to acidotropic amines and leupeptin. By fusion of LM-TK- cells to mouse Thy-1- lymphoma mutants and monitoring of surface expression of lipid-anchored proteins, we assign LM-TK- to lymphoma mutant complementation group H. This genetic assignment is matched by analysis of mannolipids of L929, LM-TK-, wild-type, and class H lymphoma mutant cells: striking similarities are seen between the two wild-type cells by contrast to the mutants. Since the differences pertain to lipids which have properties consistent with their being anchor precursors, we suggest that LM-TK- has a lesion in the synthesis of anchor precursor mannolipids.
Mol Cell Biol 1991 May
PMID:Anchoring and degradation of glycolipid-anchored membrane proteins by L929 versus by LM-TK- mouse fibroblasts: implications for anchor biosynthesis. 182 59

In a previous study, we have shown that freshly isolated glomerulosa cells possess dopamine (DA) receptors from both DA-1 and DA-2 subclasses, whereas in cultured conditions, cells exhibit dopamine receptors from the DA-1 subclass only. In the present work, we have studied the effect of DA on angiotensin-stimulated glomerulosa cells in these two experimental conditions. Our results demonstrate that in isolated cells, angiotensin II (AT) stimulates inositol phosphate accumulation, calcium influx and steroid secretion. Treatment with pertussis toxin completely blocks AT-stimulated steroid secretion and calcium influx and partially reduces inositol phosphate accumulation. DA alone has no effect on cAMP accumulation. However, in the presence of a specific DA-1 antagonist (SCH 23390), DA reduces intracellular cAMP content. Similarly, DA-like pertussis toxin produces the same inhibitory effects on AT-stimulated cells. The combined influence of DA and pertussis toxin is not additive suggesting that a 'Gi' GTP-binding protein is involved in the DA action. Specific DA antagonists indicate that these inhibitory processes are mediated through the DA-2 receptor subtype. DA may act by decreasing the intracellular calcium concentration since it reduces AT-stimulated Ca2+ influx and that both phospholipase C (PLC) and steroid accumulation are calcium dependent. Yet a direct inhibitory coupling between the DA-2 receptor and PLC may represent a second alternative since DA inhibitory effects are always present when calcium influx is artificially increased or decreased. In cultured cells, we observe an additive effect of DA and AT on aldosterone secretion, which is the result of additive interactions of the second messengers involved, namely cAMP for dopamine and inositol phosphates for angiotensin II. From these studies, we conclude that DA may exert a more versatile effect on aldosterone secretion than previously suspected.
Mol Cell Endocrinol 1991 Oct
PMID:Mechanisms involved in the interaction of dopamine with angiotensin II on aldosterone secretion in isolated and cultured rat adrenal glomerulosa cells. 183 52


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