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:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The glycosyl nature of the receptor for the peptide hormone calcitonin has been investigated in a human breast cancer cell line, T 47D. Studies have been carried out to assess the ability of various lectins and of the antibiotic tunicamycin to inhibit specific binding of calcitonin to the cells, to reduce cross-linking of photoactive calcitonin to a macromolecular receptor component and to influence calcitonin stimulation of cyclic AMP. Pre-incubation of cells with low concentrations of tunicamycin for 72 h resulted in a reduction of total specific binding by approx. 80% and a 40% reduction in calcitonin-stimulated adenylate cyclase; formation of the cross-linked receptor component was also inhibited. Wheat-germ lectin showed the most marked inhibition of total specific binding and cyclic AMP production. However, cross-linking of photoactive calcitonin to receptor component was totally inhibited by this lectin. Soya-bean lectin brought about very little reduction in total specific binding but had more profound effects on calcitonin-stimulated cyclic AMP production and cross-linking of photoactive calcitonin. Concanavalin A and lentil lectin showed some inhibition of all parameters. The data indicate that the calcitonin receptor in T 47D cells is associated with glycosyl moieties, the major contributors of which are N-acetyl-D-glucosamine residues, but N-acetyl-D-galactosamine and mannose residues are also associated.
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PMID:The calcitonin receptor on T 47D breast cancer cells. Evidence for glycosylation. 630 49

The active A1 peptide of cholera toxin was linked by a disulphide bond to the lectin of Wisteria floribunda. The resulting conjugate activated the adenylate cyclase of intact U937 or K562 cells at the same concentrations as native toxin did, but to a greater extent. Activation was inhibited by N-acetyl-D-galactosamine or by antisera to the lectin or peptide. The characteristic lag phase between addition of toxin to cells and activation of cyclase was not found with the conjugate or with free A1 peptide.
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PMID:A conjugate of the A1 peptide of cholera toxin and the lectin of Wisteria floribunda that activates the adenylate cyclase of intact cells. 636 Jul 10

We have utilized the technique of lectin-loading of SDS gels with iodinated concanavalin A and wheat germ agglutinin to identify glycoproteins in prostatic and seminal fluids as well as in prostate tissue fractions. The following subunits which bound both lectins were detected: (a) 50, 43 and 38 kDa subunits common to prostatic and seminal fluids, and an additional 55 kDa subunit which predominates only in prostatic fluid; (b) 78, 55, 50 and 43 kDa subunits in prostatic tissue cytosol and (c) 195, 170, 135, 116 and 95 kDa subunits present in the particulate fractions of prostatic tissue. Immunoblotting using specific rabbit antibodies revealed the 50 kDa band to be prostatic acid phosphatase and the 38 kDa band to be prostate-specific antigen. Interestingly, antibodies directed toward prostatic acid phosphatase were found to cross-react with the 43 kDa band. Fractionation on sucrose gradients showed that several of these particulate glycoproteins were associated with a vesicle fraction enriched in adenylate cyclase activity, implying that they are plasma membrane glycoproteins. Comparison of soluble and particulate fractions of normal and cancerous tissue homogenates was made by densitometric scanning of autoradiograms of lectin-loaded gels. Similar relative intensities of lectin-binding were obtained for corresponding proteins in normal and cancerous tissue fractions. Also, immunoblotting showed no differences in prostatic acid phosphatase or prostate-specific antigen between normal and cancerous soluble homogenate fractions. Our results suggest that major lectin-binding proteins are conserved in the transition from normal to cancerous tissue. These results may be useful in developing a multiple-marker profile of metastatic prostate cancer and for the design of imaging agents, such as monoclonal antibodies, to prominent soluble and particulate prostate glycoproteins.
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PMID:Identification of structural and secretory lectin-binding glycoproteins of normal and cancerous human prostate. 639 53

The signaling mechanisms that regulate lymphokine gene expression in the murine Th2 clone D10.G4.1 were investigated by comparing the steady state mRNA levels of six lymphokine genes in response to cellular treatment with various activators and inhibitors of several key signaling pathways. A surprising degree of differential regulation was found. All of the genes studied (IL-3, IL-4, IL-5, IL-6, IL-10, and granulocyte-macrophage (GM)-CSF) were induced by the lectin Con A and the TCR idiotype-specific mAb 3D3. However, the induction of the IL-3, IL-4, and GM-CSF genes, but not the IL-5, IL-6, and IL-10 genes, was strongly inhibited by cyclosporin A. Furthermore, IL-5, IL-6, and IL-10 genes were independently induced by IL-1 alpha, the phorbol ester PMA, and by forskolin, an activator of adenylate cyclase. Results of studies performed with use of the Ca2+ ionophore A23187 indicated that elevation of intracellular Ca2+ levels is sufficient to fully induce IL-3 and IL-4 gene expression. Protein kinase C activation was also required for full induction of the GM-CSF gene and seemed to be obligatory for maximal IL-5 gene expression. The patterns of mRNA induction by the different stimuli broadly correlated with increased rates of transcription. In addition to their induction by IL-1 alpha, the IL-5, IL-6, and IL-10 genes were also induced by mAbs to CD2 and to CD45. In contrast, adding CD45 mAb strongly inhibited the induction of IL-3, IL-4, and GM-CSF genes through TCR stimulation. These results indicate that distinct groups of lymphokine genes may be differentially regulated by signaling pathways that are activated by stimulation of the TCR and other cell surface molecules.
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PMID:TCR-dependent and -independent signaling mechanisms differentially regulate lymphokine gene expression in the murine T helper clone D10.G4.1. 791 89

The vasoactive intestinal peptide (VIP) receptor from the human melanoma cell line IGR39 has been shown to be a 60-kDa glycoprotein. Using serial lectin affinity chromatography, as well as specific glycosidases, we demonstrate that VIP receptor-linked carbohydrates are predominantly tri- or tetraantennary sialylated N-linked oligosaccharides, 27% of which are fucosylated, and some may have terminal galactose residues. Treatment of 125I-VIP receptor complexes with peptide-N4-(N-acetyl-beta-D-glucosaminyl)asparagine amidase revealed the presence of at least three N-linked carbohydrate chains/receptor polypeptide. To investigate the functional role of the carbohydrate moiety, 125I-VIP binding to IGR39 cell membranes was tested in the presence of soluble lectins. Among the lectins tested, only wheat germ agglutinin (WGA) was found to markedly inhibit VIP binding in a dose-dependent manner. Binding data indicated that the presence of the lectin led to a 3-fold increase in Kd value, from 0.15 to 0.44 nM, without any change in the number of available binding sites. The potent inhibitor of WGA binding, N,N',N"-triacetylchitotriose, completely reversed the effect of the lectin. On the other hand, VIP binding inhibition persisted even after neuraminidase treatment, suggesting that sialic acids were not directly involved. Furthermore, WGA inhibition was not abolished although most, if not all, VIP receptor oligosaccharides were converted to high mannose type structures by treating IGR39 cells with deoxymannojirimycin. Finally, whereas the pharmacological profile of VIP receptor was virtually identical, the presence of WGA greatly reduced the VIP-stimulated cAMP in IGR39 cells, indicating that the lectin alters the ability of the receptor to interact with the adenylate cyclase system.
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PMID:Structural and functional analysis of the human vasoactive intestinal peptide receptor glycosylation. Alteration of receptor function by wheat germ agglutinin. 838 3

Among the various immune abnormalities which characterize active sarcoidosis, a low proliferative response of peripheral blood lymphocytes to mitogenic lectins has long been observed. Since membrane-associated G-proteins are very likely to be crucial elements in lectin signal transduction, we investigated the binding of 5'-guanylylimidodiphosphate (GppNHp), a non hydrolyzable GTP analogue, to blood total lymphocyte membranes and to blood T-lymphocyte membranes from patients with active sarcoidosis, and from healthy control subjects. GppNHp binding was markedly decreased in peripheral cells from patients with sarcoidosis as compared to controls, suggesting the occurrence of a defect at the level of G-protein(s). A further characterization of G-proteins in these cells by means of ADP-ribose-labelling in the presence of bacterial toxins brought forward a significant decrease in the labelling of a 40 kDa protein, the major pertussis toxin substrate, in membranes from sarcoid patients, while the labelling of the major 44 kDa cholera toxin substrate proved to be unchanged with respect to control membranes. It is hypothesized that, in sarcoid lymphocytes, a defect in the negative control of adenylate cyclase mediated by the inhibitory G-protein Gi, prevents the lowering of cAMP necessary to normal mitogenic response of blood lymphocytes to stimulation. cAMP degradation by the specialized enzyme phosphodiesterase constitutes another critical step in the control of cAMP levels. Both cAMP and cGMP phosphodiesterase activities were found decreased in blood total lymphocyte preparations from sarcoid patients. With purified T-cells, although the mean cAMP and cGMP phosphodiesterase activities from sarcoid patients were found more markedly decreased with respect to healthy donors, only the decrease in cGMP phosphodiesterase was found statistically significant. The role these defects in cyclic nucleotide degradation potentially play in the disturbance of blood lymphocytes response associated with sarcoidosis is discussed.
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PMID:Impaired G-proteins and cyclic nucleotide phosphodiesterase activity in T-lymphocytes from patients with sarcoidosis. 838 56

The role of receptor binding in the toxicity, immunogenicity, and adjuvanticity of the heat-labile enterotoxin of Escherichia coli (LT) was examined by comparing native LT and LT(G33D), a B-subunit receptor binding mutant, with respect to the ability to bind to galactose and to GM1, toxicity on mouse Y-1 adrenal tumor cells, the ability to stimulate adenylate cyclase in Caco-2 cells, enterotoxicity in the patent mouse model, and oral immunogenicity and adjuvanticity. In contrast to native LT, LT(G33D) was unable to bind to the galactosyl moiety of Sepharose 4B or GM1 but did retain the lectin-like ability to bind to immobilized galactose on 6% agarose beads. LT(G33D) had no enterotoxicity in the patent mouse model but exhibited residual toxicity on mouse Y-1 adrenal tumor cells and had an ability equivalent to that of native LT to stimulate adenylate cyclase in Caco-2 cells (5,000 versus 6,900 pmol per mg of protein). In addition, LT(G33D) was unable to serve as an effective oral adjuvant for induction of immunoglobulin G or A directed against a coadministered antigen. Furthermore, LT(G33D) elicited negligible serum and mucosal antibody responses against itself. These data indicate that the toxicity, immunogenicity, and oral adjuvanticity of LT are dependent upon binding of the B subunit to ganglioside GM1.
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PMID:Role of receptor binding in toxicity, immunogenicity, and adjuvanticity of Escherichia coli heat-labile enterotoxin. 939 80

Effects of two lectins, wheat germ agglutinin (WGA) and concanavalin A (Con A), on platelet functional reactions and interaction of lectins with the platelet membrane glycoproteins (GPs) have been studied. Both lectins stimulated platelet aggregation and secretion of serotonin from platelet dense granules. The effects of WGA and Con A were blocked by specific sugars, N-acetyl-D-glucosamine and alpha-methyl-D-mannopyranoside, respectively, by adenylate cyclase activator prostaglandin E1, and by anti-GP IIb-IIIa monoclonal antibody (monAB), CRC64, that inhibits platelet interaction with fibrinogen. The data indicate that both lectins interacting with the carbohydrate moiety on the platelet surface stimulated not passive agglutination but fibrinogen--GP IIb-IIIa-dependent platelet aggregation which is coupled with the secretion from granules and activation of the intracellular systems of signal transduction. However, there were significant differences between the stimulatory effects of WGA and Con A. WGA induced more pronounced and quick platelet aggregation and stimulated several times higher serotonin secretion than Con A. In addition, adhesion studies showed that plastic-adsorbed WGA appeared to be a nonadhesive substrate, whereas Con A effectively stimulated platelet adhesion. Unlike Con A-induced platelet aggregation, adhesion to Con A substrate was not inhibited by monAB CRC64, i.e., was not dependent on GP IIb-IIIa--fibrinogen interaction. Binding of lectins with major platelet GPs was studied using immobilized WGA and Con A and platelet lysate as a source of GPs. Platelet lysate was incubated with immobilized lectins and then binding of individual GPs was evaluated using specific mono- and polyclonal antibodies. WGA binds with GP Ib and P-selectin but not with other GPs tested. Interaction of Con A with platelet GPs was less specific. This lectin binds with GP IIb-IIIa, GP Ib, GP IV, and P-selectin. Although GP Ib appeared to be the main protein which bound WGA on platelet surface, anti-GP Ib antibodies failed to affect WGA-induced platelet aggregation, but inhibited WGA-induced agglutination of fixed platelets. Thus, interaction of the WGA with GP Ib could not be considered as a major stimulus initiating WGA-dependent platelet activation and aggregation.
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PMID:Interaction of wheat germ agglutinin and concanavalin A with platelets. Stimulation of platelet functional reactions and binding with membrane glycoproteins. 966 12

The ability of membrane ABH blood group-active glycoconjugates to act as receptors of the heat-labile enterotoxin of Escherichia coli (LTh) was studied in vitro and in vivo when GM1 was blocked by the cholera toxin B subunit. Rabbits were classified as AB or H based on intestinal ABH-antigenic activities. Brush border membranes from AB rabbits contained 4 times more LTh binding sites than the H ones. LTh interaction could be inhibited by lectins that recognize ABH determinants. LTh induced a similar dose-dependent secretory response in ligated ileal loops of both types of animals. Anti-AB antibodies and Ulex europaeus I lectin could significantly reduce the fluid accumulation in AB and H rabbits, respectively. LTh caused adenylate cyclase activation even when GM1 was blocked, and this effect was abolished by the addition of specific ABH ligands. These results suggest that ABH glycoconjugates are involved in the host secretory response to LTh in rabbit intestine.
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PMID:Participation of ABH glycoconjugates in the secretory response to Escherichia coli heat-labile toxin in rabbit intestine. 1039 58

Vasoactive intestinal peptide (VIP) and nitric oxide (NO) are neurotransmitters involved in the regulation of bronchial and pulmonary vascular tone. Published studies of the effects of VIP on airway mucus secretion have yielded conflicting results. The purpose of this study was to determine the effect of VIP on mucus secretion in the ferret trachea and if this effect was influenced by NO. We used a sandwich enzyme-linked lectin assay to measure mucin secretion and a turbidimetric assay to measure lysozyme (serous cell) secretion from ferret tracheal segments. VIP (10(-7) M) increased mucin secretion over 2 h. VIP (10(-9) to 10(-5) M) stimulated mucin secretion in a dose-dependent fashion. VIP-induced mucin secretion was partially blocked by a VIP receptor antagonist (a chimeric VIP-pituitary adenylate cyclase-activating peptide analog, VIP receptor antagonist) at a 10-fold excess concentration. At all concentrations tested, neither NG-nitro-L-arginine methyl ester, an inhibitor of NO synthase, nor S-nitroso-N-acetyl-penicillamine, an NO donor, had any significant effect on constitutive or VIP-induced mucus secretion. We conclude that VIP-stimulated mucin and lysozyme secretion was both time dependent and dose dependent and that NO neither stimulates nor inhibits mucus secretion in the ferret trachea.
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PMID:Vasoactive intestinal peptide stimulates mucus secretion, but nitric oxide has no effect on mucus secretion in the ferret trachea. 1664 89


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