Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wheat germ agglutinin, but not concanavalin A or soybean lectin, inhibited the basal-and stimulated-adenylate cyclase activity which was present in a plasma membrane preparation from the rat pancreas. The inhibition by wheat germ agglutinin was rapid and sustained. It was of the non-competitive type and never exceeded 20% for Gpp (NH) p- and NaF-stimulated adenylate cyclase activity. The inhibition of secretin-stimulated activity was also non-competitive but more pronounced (57% inhibition at a wheat germ agglutinin concentration of 20 microgram/ml). For the C-terminal octapeptide of cholecystokinin-pancreozymin (OC-PZ)-stimulated cyclase, the inhibition amounted to 68% and was of a mixed type (both competitive and non-competitive). This last observation might be explained by the competitive inhibition exerted by wheat germ agglutinin on the binding of peptides of the OC-PZ family to their membrane specific receptors. The various inhibitory effects of wheat germ agglutinin were completely suppressed by incubating the membranes in the presence of ovomucoid, a N-acetyl-D-glucosamine rich glycoprotein. The possible functional implication of these results is discussed.
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PMID:Wheat germ agglutinin inhibits basal- and stimulated-adenylate cyclase activity as well as the binding of [3H] caerulein to rat pancreatic plasma membranes. 56 9

Bordetella pertussis, the pathogen responsible for whooping cough, releases a soluble calmodulin-sensitive adenylate cyclase into its culture medium. Several investigators have shown that the partially purified adenylate cyclase is capable of entering animal cells and elevating intracellular cAMP levels [Confer, D. L., & Eaton, J. W. (1982) Science 217, 948-950; Shattuck, R. L., & Storm, D. R. (1985) Biochemistry 24,6323-6328]. However, the mechanism for entry of the catalytic subunit of the adenylate cyclase into animal cells is unknown. Recently, it was determined that the purified catalytic subunit of the enzyme is unable to enter animal cells [Masure, H. R., Oldenburg, D. J., Donovan, M. G., Shattuck, R. L., & Storm, D. R. (1988) J. Biol. Chem. 263, 6933-6940]. On the basis of these data and other observations, we hypothesized that the culture medium of B. pertussis contains one or more additional polypeptides which facilitate entry of the adenylate cyclase catalytic subunit into animal cells. In this study, we report that a cell-invasive preparation of B. pertussis adenylate cyclase was rendered noninvasive after passage through a wheat germ lectin-agarose column. A fraction was eluted from the wheat germ lectin-agarose column with N-acetyl-D-glucosamine. This fraction, when combined with the noninvasive adenylate cyclase, was able to restore the ability of the adenylate cyclase preparation to enter neuroblastoma cells and increase intracellular cAMP levels. Furthermore, the fraction eluted from the wheat germ lectin-agarose column was found to be trypsin and chymotrypsin sensitive, suggesting that this material was proteinaceous.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Isolation of a protein fraction from Bordetella pertussis that facilitates entry of the calmodulin-sensitive adenylate cyclase into animal cells. 255 96

Covalent labeling of the canine renal parathyroid hormone receptor with [125I]bPTH(1-34) reveals several major binding components that display characteristics consistent with a physiologically relevant adenylate cyclase linked receptor. Through the use of the specific glycosidases neuraminidase and endoglycosidase F and affinity chromatography on lectin-agarose gels, we show here that the receptor is a glycoprotein that contains several complex N-linked carbohydrate chains consisting of terminal sialic acid and penultimate galactose in a beta 1,4 linkage to N-acetyl-D-glucosamine. No high mannose chains or O-linked glycans appear to be present. The peptide molecular weight of the deglycosylated labeled receptor is 62,000 [or 58,000 if the mass of bPTH(1-34) is excluded]. The binding of [125I]bPTH(1-34) to the receptor is inhibited in a dose-dependent fashion by wheat-germ agglutinin, but not by either succinylated wheat-germ agglutinin or Ricinus communis lectin, suggesting that terminal sialic acid may be involved in agonist binding. A combination of lectin affinity chromatography and immunoaffinity chromatography affords a 200-fold purification of the covalently labeled receptor.
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PMID:The canine renal parathyroid hormone receptor is a glycoprotein: characterization and partial purification. 282 60

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

We have examined the interaction of certain forms of mouse (m) tumor and bovine (b) pituitary TSH with standard bTSH on the activation of adenylate cyclase in human thyroid membranes. Tumor extract, serum from tumor-bearing mice, culture medium from dispersed cell incubations, and two preparations of purified bTSH (Sigma and Pierce) were fractionated on Sephadex G-100 (1.2 X 200 cm). For each fraction, TSH bioactivity was measured by stimulation of adenylate cyclase activity in human thyroid membranes, and immunoactivity was determined by RIA. On G-100, Pierce bTSH had multiple immunoactive components with partition coefficients (Kav) of 0.28-0.32 and ratios of biological over immunological activity (B/I) of 0.59-1.42. Sigma bTSH, mouse tumor, serum, and medium were even more heterogeneous (Kav = 0.23-0.32), with a lower range of B/I (0.04-1.0). When single doses (125-2000 ng) of those fractions with the highest Kav (0.30-0.32) and lowest B/I (0.04-0.51) were mixed with multiple doses (200-10,000 microU) of Armour TSH standard (B/I = 1), there was 30-56% inhibition of adenylate cyclase activity stimulation. Double reciprocal plots showed competitive inhibition for the low B/I forms from all sources, except for a medium form which showed mixed inhibition. The medium form had the highest inhibitory activity. There were no inhibitors in G-100 fractions from the Kav regions devoid of TSH immunoactivity or from the same Kav regions of normal mouse serum. To determine the chemical differences between different forms, affinity chromatography on Concanavalin A, wheat germ agglutinin, and soybean agglutinin was employed. Compared with the apparent higher molecular weight form with higher B/I, the apparent lower molecular weight form with lower B/I contained decreased amounts or availability of alpha-mannose and increased amounts or availability of beta-N-acetyl-D-galactosamine and/or beta-galactose; both forms appear to contain similar beta-N-acetyl-D-glucosamine residues, presumably in the inner core.
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PMID:Naturally occurring forms of thyrotropin with low bioactivity and altered carbohydrate content act as competitive antagonists to more bioactive forms. 664 28

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

Although Vibrio cholerae is a human pathogen its primary habitat are aquatic environments. In this environment, V.cholerae takes advantage of the abundance of zooplankton, whose chitinous exoskeletons provide a nutritious surface. Chitin also induces the developmental programme of natural competence in several species of the genus Vibrio. Because the chitin surface can serve as the sole carbon source for V.cholerae, the link between carbon catabolite repression and chitin-induced natural competence for transformation was investigated in this study. Provision of competing phosphoenolpyruvate: carbohydrate phosphotransferase system (PTS)-dependent carbon sources in addition to chitin significantly lowered natural transformability. These sugars are known to interfere with the accumulation of 3',5'-cyclic AMP (cAMP); therefore, the contributions of the cAMP-producing enzyme, adenylate cyclase and the cAMP receptor protein (CRP) to chitin surface colonization, chitin degradation and natural transformation were also analysed. The results provided here indicate that cAMP and CRP are important in at least three interlinked areas of the chitin-induced natural competence programme. First, cAMP and CRP are required for the efficient colonization of the chitin surface; second both contribute to chitin degradation and utilization, and third, cAMP plus CRP play a role in increasing competence gene expression. These findings highlight the complex regulatory circuit of chitin-induced natural competence in V.cholerae.
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PMID:Chitin colonization, chitin degradation and chitin-induced natural competence of Vibrio cholerae are subject to catabolite repression. 2222