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)

It has been shown that the human fat cell adenylate cyclase is activated by prostaglandins. Of the prostaglandins tested the E-type by causing about a 3-fold increase of enzyme activity, was more effective than the F-prostaglandins. Prostaglandin A2 had no stimulatory effect. Activation by prostaglandin E1 was not influenced by beta-adrenergic blockade in contrast to stimulation by epinephrine. Pretreatment of fat cells with trypsin resulted in an abolishment of PTH-sensitivity, but had no effect on prostaglandin responsiveness. These results suggest that the human fat cell adenylate cyclase is coupled to at least three distinct types of hormone receptors.
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PMID:Adenylate cyclase of human fat cell ghosts. Stimulation of enzyme activity by prostaglandins. 90 33

Cytosol prepared from rat epididymal fat cells by centrifugation at 100,000 X g for 1 hr was found to enhance the basal and epinephrine-sensitive adenylate cyclase [EC 4.6.1.1; ATP pyrophosphate-lyase (cyclizing)] of fat cell ghosts. Cholera toxin also stimulated adenylate cyclase and increased the response to epinephrine in fat cells. A possible relationship between the adenylate cyclase modifying activities of cytosol and the effects of cholera toxin was sought. Cytosol from freshly prepared fat cells added to ghosts prepared from cells that had been exposed to toxin for varying periods showed a progressive loss of responsiveness to cytosol epinephrine-enhancing activity. The effect appeared within 15 min after toxin exposure, a full 30 min before any direct effect of toxin on adenylate cyclase was seen. Since exposure to toxin decreased membrane response to cytosol epinephrine-enhancing activity, the possibility that epinephrine-enhancing activity in cytosol might be altered by toxin was explored. Cytosol from cells exposed to toxin for varying periods lost epinephrine-enhancing activity to an appreciable degree within 15 min. Examination of these early events after exposure to toxin should clarify the way in which this bacterial substance affects mammalian cells. The cytosol epinephrine-enhancing activity was destroyed by boiling for 3 min and was partially inactivated by trypsin. It was nondialyzable and stable at -70 degrees.
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PMID:Stimulation of epinephrine-sensitive fat cell adenylate cyclase by cytosol: effect of cholera toxin. 105 43

Iodinated derivatives of glucagon containing an average of 1 to 5 g-atoms of 127I per mol have been prepared by reacting the hormone with increasing amounts of iodine monochloride. Their iodoamino acid composition has been determined by ion-exchange chromatography and electrophoresis, following hydrolysis by pronase. Iodination of the two tyrosyl residues occurs first and is nearly complete after addition of a 4-fold molar excess of ICl. Iodination of the single histidyl residue is a later event and does not exceed an average of one atom per residue. Hydrolysis of iodoglucagon by trypsin and subsequent separation of the iodotyrosyl peptides shows that iodine is equally distributed between tyrosyl residues 10 and 13. Crude iodoglucagon containing an average of 1 g-atom of iodine per mol has been resolved into several components of differing iodine content and iodoamino acid composition by chromatography on DEAE-cellulose. Monoiodoglucagon isolated by this procedure shows a single band when analyzed by polyacrylamide gel electrophoresis. Iodoglucagons containing an average of 1 to 4 g-atoms of iodine per mol are more potent than native glucagon in their ability to stimulate adenylate cyclase activity and to bind to glucagon receptors of liver cell membranes of the rat. The maximal increase in biological potency occurring upon iodination is about 5-fold with respect to adenylate cyclase activity, and 2-fold with respect to binding to receptors; tetra and triiodinated derivatives show, respectively, the highest potency. Similar effects occur whether inactivation by liver membranes is inhibited or not, indicating an enhancement in the intrinsic affinity of iodoglucagon for the receptors. Iodination beyong 4 g-atoms per mol slightly decreases the affinity of the hormone for adenylate cyclase and for the receptors. Iodination causes a 2-20 fold decrease in the ability of liver plasma membranes and of blood plasma to inactivate glucagon in vitro; these effects correlate with the degree of iodination. With liver microsomal membranes, a decrease in glucagon inactivation occurs only at iodine contents exceeding 4 g-atoms per mol, and lower degrees of iodination result in opposite effects. Monoiodination causes a 4-6-fold increase in the plasma concentration of glucagon within the first 18 min following a single intrvenous injection of the hormone to rats. More extensive iodination results, in addition, in a marked decrease in the rate of dissappearance of glucagon from the blood. The immunological reactivity of glucagon is little affected by monoidination, but strongly depressed by higher degrees of iodination...
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PMID:Iodoglucagon. Preparation and characterization. 114 Feb 1

The complete amino acid sequence was determined for bovine ubiquitin, and adenylate cyclase stimulating polypeptide, which is probably represented universally in living cells. Ubiquitin has a molecular weight of 8451 and consists of a single polypeptide chain containing 74 amino acid residues. It contains four arginine residues but no cysteine or trytophan residues. The first 61 amino acid residues were obtained by automated Edman degradations. Tryptic digestion of maleated ubiquitin yielded four peptide fragments that were resolved by molecular sieve chromatography and coded in order of decreasing chain length (MT-1, MT-2, MT-3, and MT-4). The automated sequenator determinations on native ubiquintin provided overlapping sequence data for three of these fragments that gave an order of MT-1, MT-3, and then MT-2; Peptide MT-4, a dipeptide, was therefore assigned to the C terminus, and the placement of peptide MT-2 was corroborated by analysis of data from carboxypeptidase digestions of maleated ubiquitin. Peptide MT-2 was domaleated and sequenced by manual Edman degradations through a single lysine residue. It was cleaved at this residue with trypsin, and the two resultant peptides were separated by ion-exchange chromatography. Manual sequencing of the C-terminal demaleated tryptic peptide of MT-2 completed the sequence of MT-2 and that of native ubiquitin. The sequence of ubiquitin was further confirmed and supported by amino acid and parital sequence anlysis of fragments obtained by digestion of maleated ubiquitin with chymotrypsin or staphylococcal protease.
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PMID:The complete amino acid sequence of ubiquitin, an adenylate cyclase stimulating polypeptide probably universal in living cells. 117 Aug 80

Plasma membranes prepared from rat renal cortex contain both a parathyroid hormone-sensitive adenylate cyclase and a potent proteolytic activity which degrades the hormone into peptide fragments. The degree and pattern of degradation was determined by subjecting incubation mixtures to gel filtration and ion exchange chromatography. Estimation of the degree of degradation by acid precipitation of the intact hormone was inadequate since metabolism of the hormone apparently generated acid-insoluble fragments. When parathyroid hormone was incubated with membrane fraction, the capacity of its stimulatory effect on adenylate cyclase decreased steadily. This decrease of PTH activitiy could be closely related to the degradation of intact hormone by the same membrane preparation. The adenylate cyclase and degradative activity appeared to exist in similar membrane structures since they could not be separated by centrifugation through sucrose density gradients. The degradation of the hormone could not be inhibited by Trasylol and pancreatic or soybean trypsin inhibitors and was only slightly inhibited by ribonuclease and benzamidine. Histone (1 mg per ml), on the other hand, was able to decrease the degradation of the hormone and prevent the loss of its activity. Radioimmunoassay of the incubation mixtures showed that the rapid degradation of both amino- and carboxy-terminal regions of the hormone was prevented by histone. The oxidized, inactive hormone was also degraded to the same extent by the renal cortical membrane. Furthermore, the degradative activity was also found in plasma membrane preparations of renal medulla and liver. This lack of hormone and tissue specificity suggests that similar degradative activity exists in all tissues and that caution should be exercised in estimating hormonal potency based on activation of adenylate cyclase.
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PMID:Interaction of parathyroid hormone with membranes of kidney cortex: degradation of the hormone and activation of adenylate cyclase. 119 1

Adenylate cyclase activity of a rat embryo fibroblast cell line (F111) is markedly increased by brief treatment with 1:300 trypsin. The degree of stimulation depends upon the length of time the cells are treated and the concentration of trypsin. Crystalline trypsin produced a stimulation similar to that obtained with 1:300 trypsin. Further, the addition of soybean trypsin inhibitor blocked the stimulation of adenylate cyclase by 1:300 trypsin. Trypsin-treated adenylate cyclase responds to PGE1, but there is no increase over that of untreated enzyme. This result and the increase in fluoride-stimulated levels of activity suggest that the trypsin is acting upon the catalytic unit of the enzyme.
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PMID:Adenylate cyclase stimulation by trypsin. 120 92

We have characterized the ANF-R2 receptor-mediated inhibition of adenylate cyclase with respect to its modulation by several regulators. ANF (99-126) inhibits adenylate cyclase activity only in the presence of guanine nucleotides. The maximal inhibition (approximately 45%) was observed in the presence of 10-30 microM GTP gamma S, and at higher concentrations, the inhibitory effect of ANF was completely abolished. ANF-mediated inhibition was not dependent on the presence of monovalent cations, however Na+ enhanced the degree of inhibition by about 60%, whereas K+ and Li+ suppressed the extent of inhibition by about 50%. On the other hand, divalent cation, such as Mn2+ decreased the degree of inhibition in a concentration dependent manner, with an apparent Ki of about 0.7 mM, and at 2 mM; the inhibition was completely abolished. In addition, proteolytic digestion of the membranes with trypsin (40 ng/ml) resulted in the attenuation of ANF-mediated inhibition of adenylate cyclase. Other membrane disrupting agents such as neuraminidase and phospholipase A2 treatments also inhibited completely, the ANF-mediated inhibition of enzyme activity. N-Ethylmaleimide (NEM), phorbol ester and Ca(2+)-phospholipid dependent protein kinase (C-kinase) which have been shown to interact with inhibitory guanine nucleotide regulating protein (Gi) also resulted in the attenuation of ANF-mediated inhibition of adenylate cyclase activity. These results indicate that in addition to the Gi, the phospholipids and glycoproteins may also play an important role in the expression of ANF-R2 receptor-mediated inhibition of adenylate cyclase.
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PMID:Characterization of ANF-R2 receptor-mediated inhibition of adenylate cyclase. 132 94

Mast cells are hypothesized to participate in processes leading to tissue fibrosis in human lung and skin. To explore the possible involvement of mast cell mediators in fibrogenesis, the mitogenic activity of mast cell tryptase from human lung was examined in vitro. The results indicate that human tryptase is a potent inducer of DNA synthesis in fibroblasts from multiple sources, including human lung. As demonstrated by mitogenic responses in fibroblasts, but not in vascular smooth muscle cells, tryptase is a mitogen with target cell specificity. Additionally, specificity is demonstrated by the differences in mitogenic activity of tryptase in comparison with thrombin, a structurally related mitogenic proteinase. Examination of the mitogenic effects of tryptase in the presence of other mitogens reveals synergy with mitogens that act through receptors coupled to intrinsic tyrosine kinases (insulin, epidermal growth factor, and basic fibroblast growth factor) or to G proteins (thrombin and serotonin). In the latter case, studies in Chinese hamster lung fibroblasts using specific receptor agonists and antagonists or receptor-transfected cell lines reveal a requirement for the activation of a G protein (Gi) negatively coupled to adenylate cyclase to act synergistically with tryptase. These data establish that human tryptase is a potent and specific mitogen in vitro and suggest that mitogenic signals generated by tryptase can interact synergistically with signals generated by both tyrosine kinase-coupled and G protein-coupled growth factor receptors.
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PMID:Human tryptase as a potent, cell-specific mitogen: role of signaling pathways in synergistic responses. 159 Apr 4

PC-3 human prostatic tumor sublines have been previously isolated which exhibit striking differences in their invasive and metastatic phenotypes. This work has been extended here to measure and compare the levels of kinesin, a microtubule-dependent translocator molecule, in the PC-3 sublines. Western blots, slot blots, radiolabeling, and immunoprecipitation analysis showed that kinesin was expressed in the highly invasive and metastatic sublines at levels which were elevated above the base-line levels observed in the parent PC-3 cells. In comparison, kinesin was not expressed in detectable amounts in the noninvasive cell lines. The conditioned medium of the metastatic PC-3 sublines contained a heat- and trypsin-sensitive protein which exhibited a dosage-dependent capacity to stimulate increased kinesin expression, type IV collagenase secretion, and invasion of Matrigel by the metastatic sublines. The noninvasive sublines failed to secrete a similar stimulatory factor(s) or respond to the conditioned medium of metastatic sublines. Various growth factors and cytokines tested (platelet-derived growth factor, epidermal growth factor, insulin-like growth factor, formylmethionineleucinephenylalanine) had no significant effect on either kinesin expression or protease secretion and invasion. Pertussis toxin blocked the stimulatory effects of the conditioned medium, but other agents known to interfere with adenylate cyclase pathways (i.e., cholera toxin, forskolin, 8-bromoadenosine) failed to block stimulation. The data show for the first time that kinesin, protease secretion, and the resulting invasion process may be regulated in a coordinated manner by an autocrine factor(s) which activates G-protein-dependent processes.
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PMID:Regulation of kinesin expression and type IV collagenase secretion in invasive human prostate PC-3 tumor sublines. 165 72

We observed that culture medium conditioned with fetal rat long bones contained peptides immunologically related to the parathyroid hormone-related peptide of malignancy (PTHrP) and stimulated cyclic AMP production in canine renal cortical membranes. Because the adenylate cyclase stimulating activity (CSA) of the medium increased when bone resorption was stimulated, it was suspected that these peptides were stored in the matrix and released during the resorption process. In this work, we extracted the noncollagenous proteins of fetal rat long bones and found that the extract contained significant amounts of CSA. The biologic activity of the extract was abolished after trypsin digestion and eluted at 24 and 37 kD on filtration HPLC. The CSA of bone extract and of both HPLC peaks could be inhibited by 3-34 and 7-34 parathyroid hormone analogs. It was not blocked by an antiserum directed against the N-terminal region of parathyroid hormone, but it was significantly inhibited after an overnight preincubation with an antiserum directed against the 1-11 fragment of PTHrP. One band migrating at 18 kD could be visualized after SDS-PAGE electrophoresis of bone extract and immunoblotting with the anti-PTHrP antiserum. We conclude that an adenylate cyclase stimulator immunologically similar to PTHrP is present in the matrix of fetal rat long bones. Adenylate cyclase stimulating peptides of lower molecular weight found in bone-conditioned medium could be active fragments formed by proteolysis during the resorption process.
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PMID:Adenylate cyclase stimulating activity immunologically similar to parathyroid hormone-related peptide can be extracted from fetal rat long bones. 166 3


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