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)

Enterotoxin derived from three clinical isolates of Yersinia enterocolitica was compared with the heat-stable enterotoxin of Escherichia coli. Both toxins were biologically active in infant mice examined at 2 h and in ligated rabbit ileal loops at 6 h. Neither substance, however, produced changes in ligated ileal loops at 18 h or in Chinese hamster ovary or Y1 adrenal tissue cultures. In addition, both Y. enterocolitica enterotoxin concentrated approximately 20 times by ammonium sulfate precipitation and ultrafiltration and a similarly prepared sample of E. coli heat-stable enterotoxin stimulated the activity of guanylate cyclase but not that of adenylate cyclase in infant mouse intestine. These findings suggest that the role of enterotoxin in the pathogenesis of intestinal Y.enterocolitica infection may be similar to that of heat-stable enterotoxin in E. coli diarrhea.
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PMID:Mechanism of action of Yersinia enterocolitica enterotoxin. 3 94

Yersinia pestis plague murine toxin has been found to inhibit the mobilization of free fatty acids in mice in a manner similar to that of beta-adrenergic blocking agents. The blockage is detectable 75 min after injection of the toxin (1 to 2 mean lethal doses). The degree of inhibition was directly correlated with the toxicity of a given toxin preparation. Agents such as cholera toxin or glucagon, with apparently distinct receptors from beta-adrenergic receptors, stimulated adenylate cyclase and lipolysis and effectively modified toxicity. Likewise, cyclic adenosine 3',5'-monophosphate bypassed the toxin block and antagonized toxicity. Energy-rich compounds such as fatty acids, organic acids, and glucose effectively modified the intoxication process. The biological activity of plague toxin showed profound temperature sensitivity. Mice placed at 5 degrees C were highly susceptible to the effects of the toxin, whereas mice placed at 37 degrees C were totally resistant to intoxication. Results showed that plague toxin cannot block epinephrine-induced mobilization of free fatty acids in mice placed at 37 degrees C. These studies suggested that plague toxin acts at the receptor level in a manner similar to that of beta-adrenergic blocking agents. A complete, analogous activity was shown between toxin and known beta-adrenergic antagonists in their effect on beta-adrenergic agonist action in stimulating lipolysis. It is hypothesized that, since toxin shows no in vitro activity, it is in some way modified in animals.
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PMID:Beta-adrenergic blocking activity of Yersinia pestis murine toxin. 19 77

Substantial evidence suggests a link between infections with Yersinia enterocolitica (YE) and Graves' disease. We have now examined the sera of 72 patients recovering from YE infection for immunoglobulins that interacted with the TSH receptor in human thyroid membranes. Compared with controls, in concentrations between 1 and 4 mg/mL, patient IgG produced a significant, concentration-dependent inhibition of TSH binding (p less than 0.001) and stimulation of adenylate cyclase activity (p less than 0.005-0.05). Whereas IgG from normal individuals caused no stimulation of adenylate cyclase, IgG from controls caused some concentration-dependent displacement of TSH, as previously reported. However, IgG from convalescents of YE infections was significantly more potent than normal IgG in reducing the binding of TSH to the membrane. Thus, at each examined concentration, YE patients' IgG displaced more TSH than IgG from normal controls. For each milligram per milliliter increment of IgG in the assay, patients' IgG caused a 10.2% inhibition of TSH binding (r -0.90, p less than 0.001), significantly greater than that seen with normal IgG (p less than 0.02). The present studies provide the first demonstration that IgG of patients recovering from YE infections react with the human TSH receptor. The antibodies presumably are produced against the TSH-binding protein present in YE. However, in view of lack of evidence for thyroid dysfunction in the sera of patients recovering from yersiniosis and the presence of TSH-binding proteins in other bacteria, we postulate that infection with YE is neither necessary nor sufficient to cause thyroid autoimmune disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunoglobulins of patients recovering from Yersinia enterocolitica infections exhibit Graves' disease-like activity in human thyroid membranes. 168 56

In spite of the resemblance of the clinical picture of gastrointestinal yersiniosis and acute dysentery, material differences underlie the pathogenesis of these diseases. Yersiniosis is marked by the predominance of an increase in the content of PGF2 alpha, whereas acute dysentery by an increase in the content of PGE, which may be accounted for by greater intensity of the allergic manifestations in yersiniosis patients as compared with dysentery. Shigellosis runs its course in the presence of the prevailing influence of the guanylate cyclase system, whereas yersiniosis in that of the adenylate cyclase. This is likely to be related to graver destructive lesions in the colonic mucosa in acute dysentery.
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PMID:[Prostaglandins and cyclic nucleotides in the gastrointestinal form of yersiniosis]. 269 95

Cultures of blood lymphocytes from 16 patients with Graves' disease (GD) and 14 matched controls were studied. Incorporation of [14C]thymidine was significantly increased in unstimulated cultures of GD lymphocytes, while the incorporation after stimulation with polyclonal activators (concanavalin A, pokeweed mitogen, phytohaemagglutinin), microbial antigens (E. coli, Candida albicans extract, purified protein derivative of tuberculin, Yersinia enterocolitica serotype 3) and subcellular fractions of human thyroid antigens did not differ from the controls. Due to the increased incorporation in unstimulated cultures, stimulation index is not suitable as an indicator of lymphocyte sensitization. After polyclonal activation or stimulation with thyroid antigens the lymphocytes were cultured for up to 21 days, and the supernatants were investigated for thyroid adenylate cyclase stimulating immunoglobulins (TACSI). No TACSI were demonstrated in supernatants of the lymphocyte cultures neither afer polyclonal activation nor after specific stimulation with several thyroid antigens.
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PMID:In vitro lymphocyte proliferation in response to polyclonal activators and microbial antigens, and production of immunoglobulins stimulating thyroid adenylate cyclase in Graves' disease. 689 86

Pathogenic bacteria of the genus Yersinia release in vitro a set of antihost proteins called Yops. Upon infection of cultured epithelial cells, extracellular Yersinia pseudotuberculosis transfers YopE across the host cell plasma membrane. To facilitate the study of this translocation process, we constructed a recombinant Yersinia enterocolitica strain producing YopE fused to a reporter enzyme. As a reporter, we selected the calmodulin-dependent adenylate cyclase of Bordetella pertussis and we monitored the accumulation of cyclic AMP (cAMP). Since bacteria do not produce calmodulin, cyclase activity marks the presence of hybrid enzyme in the cytoplasmic compartment of the eukaryotic cell. Infection of a monolayer of HeLa cells by the recombinant Y. enterocolitica strain led to a significant increase of cAMP. This phenomenon was dependent not only on the integrity of the Yop secretion pathway but also on the presence of YopB and/or YopD. It also required the presence of the adhesin YadA at the bacterial surface. In contrast, the phenomenon was not affected by cytochalasin D, indicating that internalization of the bacteria themselves was not required for the translocation process. Our results demonstrate that Y. enterocolitica is able to transfer hybrid proteins into eukaryotic cells. This system can be used not only to study the mechanism of YopE translocation but also the fate of the other Yops or even of proteins secreted by other bacterial pathogens.
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PMID:Translocation of a hybrid YopE-adenylate cyclase from Yersinia enterocolitica into HeLa cells. 788 36

It was shown that "mouse" toxin of Yersinia pestis injected into the rat tail vein (LD100) caused a 2-fold decrease in the glycogen content in the liver and the glucose content in the blood. The Bmax of beta-adrenoceptors as well as basal, forskolin, 5-guanylyl imidodiphosphate, fluoride and glucagon-stimulated liver adenylate cyclase (AC) activities did not change in all periods of intoxication. After 5 hours of intoxication isoproterenol had no effect on AC; however, the cAMP content was increased 1.5 times in comparison with control. These data suggest that plague intoxication has no effect on cAMP-dependent regulation of glycogenolysis and gluconeogenesis in the liver. The action mechanism of toxin(s) on carbohydrate metabolism in also unrelated to the decrease in Bmax for alpha 1 adrenergic receptors in liver membranes, whose number increased 1.3 and 1.5 times after 1 and 2 hours of intoxication.
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PMID:[Hormonal regulation of carbohydrate metabolism in the liver in plague intoxication]. 818 Feb 75

Pathogenic yersiniae secrete a set of antihost proteins, called Yops, by a type III secretion mechanism. Upon infection of cultured epithelial cells, extracellular Yersinia pseudotuberculosis and Yersinia enterocolitica translocate cytotoxin YopE across the host cell plasma membrane. Several lines of evidence suggest that tyrosine phosphatase YopH follows the same pathway. We analyzed internalization of YopE and YopH into murine PU5-1.8 macrophages by using recombinant Y. enterocolitica producing truncated YopE and YopH proteins fused to a calmodulin-dependent adenylate cyclase. The YopE-cyclase and YopH-cyclase hybrids were readily secreted by Y. enterocolitica. The N-terminal domain required for secretion was not longer than 15 residues of YopE and 17 residues of YopH. Internalization into eukaryotic cells, revealed by cAMP production, only required the N-terminal 50 amino acid residues of YopE and the N-terminal 71 amino acid residues of YopH. YopE and YopH are thus modular proteins composed of a secretion domain, a translocation domain, and an effector domain. Translocation of YopE and YopH across host cell's membranes was also dependent on the secretion of YopB and YopD by the same bacterium. The cyclase fusion approach could be readily extended to study the fate of other proteins secreted by invasive bacterial pathogens.
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PMID:Identification of the YopE and YopH domains required for secretion and internalization into the cytosol of macrophages, using the cyaA gene fusion approach. 861 31

Pathogenic yersiniae deliver a number of different effector molecules, which are referred to as Yops, into the cytosol of eukaryotic cells via a type III secretion system. To identify the regions of YopE from Yersinia pseudotuberculosis that are necessary for its translocation across the bacterial and eukaryotic cellular membranes, we constructed a series of hybrid genes which consisted of various amounts of yopE fused to the adenylate cyclase-encoding domain of the cyclolysin gene (cyaA) of Bordetella pertussis. By assaying intact cells for adenylate cyclase activity, we show that a YopE-Cya protein containing just the 11 amino-terminal residues of YopE is efficiently exported to the exterior surface of the bacterial cell. Single amino acid replacements of the first seven YopE residues significantly decreased the amount of reporter protein detected on the cell surface, suggesting that the extreme amino-terminal region of YopE is recognized by the secretion machinery. As has recently been shown for the Y. enterocolitica YopE protein (M.-P. Sory, A. Boland, I. Lambermont, and G. R. Cornelis, Proc. Natl. Acad. Sci. USA 92:11998-12002, 1995), we found that export to the cell surface was not sufficient for YopE-Cya proteins to be delivered into the eukaryotic cytoplasm. For traversing the HeLa cell membrane, at least 49 yopE-encoded residues were required. Replacement of leucine 43 of YopE with glycine severely affected the delivery of the reporter protein into HeLa cells. Surprisingly, export from the bacterial cell was also not sufficient for YopE-Cya proteins to be released from the bacterial cell surface into the culture supernatant. At least 75 residues of YopE were required to detect activity of the corresponding reporter protein in the culture supernatant, suggesting that a release domain exists in this region of YopE. We also show that the chaperone-like protein YerA required at least 75 YopE residues to form a stable complex in vitro with YopE-Cya proteins and, furthermore, that YerA is not required to target YopE-Cya proteins to the secretion complex. Taken together, our results suggest that traversing the bacterial and eukaryotic membranes occurs by separate processes that recognize distinct domains of YopE and that these processes are not dependent on YerA activity.
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PMID:Delineation and mutational analysis of the Yersinia pseudotuberculosis YopE domains which mediate translocation across bacterial and eukaryotic cellular membranes. 895 6

Extracellular Yersinia disarm the immune system of their host by injecting effector Yop proteins into the cytosol of target cells. Five effectors have been described: YopE, YopH, YpkA/YopO, YopP and YopM. Delivery of these effectors by Yersinia adhering at the cell surface requires other Yops (translocators) including YopB. Effector and translocator Yops are secreted by the type III Ysc secretion apparatus, and some Yops also need a specific cytosolic chaperone, called Syc. In this paper, we describe a new Yop, which we have called YopT (35.5kDa). Its secretion required an intact Ysc apparatus and SycT (15.0kDa, pl4.4), a new chaperone resembling SycE. Infection of macrophages with a Yersinia, producing a hybrid YopT-adenylate cyclase, led to the accumulation of intracellular cAMP, indicating that YopT is delivered into the cytosol of eukaryotic cells. Infection of HeLa cells with a mutant strain devoid of the five known Yop effectors (deltaHOPEM strain) but producing YopT resulted in the alteration of the cell cytoskeleton and the disruption of the actin filament structure. This cytotoxic effect was caused by YopT and dependent on YopB. YopT is thus a new effector Yop and a new bacterial toxin affecting the cytoskeleton of eukaryotic cells.
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PMID:YopT, a new Yersinia Yop effector protein, affects the cytoskeleton of host cells. 972 29


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