Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells.
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It is shown here that EF is an adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1] produced by Bacillus anthracis in an inactive form and nearly equals that of the most active known cyclase.Abstract:Â
Anthrax toxin is composed of three proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). These proteins individually cause no known physiological effects in animals but in pairs produce two toxic actions. Injection of PA with LF causes death of rats in 60 min, whereas PA with EF causes edema in the skin of rabbits and guinea pigs. The mechanisms of action of these proteins have not been determined. It is shown here that EF is an adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] produced by Bacillus anthracis in an inactive form. Activation occurs upon contact with a heat-stable eukaryotic cell material. The specific activity of the resulting adenylate cyclase nearly equals that of the most active known cyclase. In Chinese hamster ovary cells exposed to PA and EF, cAMP concentrations increase without a lag to values about 200-fold above normal, remain high in the continued presence of toxin, and decrease rapidly after its removal. The increase in cAMP is completely blocked by excess LF. It is suggested that PA interacts with cells to form a receptor system by which EF and perhaps LF gain access to the cytoplasm.read more
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Proteolytic Inactivation of MAP-Kinase-Kinase by Anthrax Lethal Factor
Nicholas S. Duesbery,Craig P. Webb,Stephen H. Leppla,Valery M. Gordon,Kurt Klimpel,Terry D. Copeland,Natalie G. Ahn,M Oskarsson,Kenji Fukasawa,Ken D. Paull,George F. Vande Woude +10 more
TL;DR: It is shown that LF is a protease that cleaves the amino terminus of mitogen-activated protein kinase kinases 1 and 2 and that this cleavage inactivates MAPKK1 and inhibits the MAPK signal transduction pathway.
Journal ArticleDOI
Identification of the cellular receptor for anthrax toxin.
Kenneth A. Bradley,Jeremy Mogridge,Jeremy Mogridge,Michael Mourez,Robert J. Collier,John A. Young +5 more
TL;DR: The cloning of the human PA receptor is described using a genetic complementation approach and a soluble version of this domain can protect cells from the action of the toxin.
Journal ArticleDOI
Structure and function of cholera toxin and the related Escherichia coli heat-labile enterotoxin.
TL;DR: The recent elucidation of the three-dimensional structure of the heat-labile enterotoxin has provided an opportunity to examine and compare the correlations between structure and function of the two toxins, which may improve understanding of the disease process itself and illuminate the role of the toxin in studies of signal transduction and G-protein function.
Journal ArticleDOI
Anthrax toxin: receptor binding, internalization, pore formation, and translocation.
John A. T. Young,R. John Collier +1 more
TL;DR: Advances in understanding the entry process include insights into how PA recognizes its two known receptors and its ligands, LF and EF; how the PA:receptor interaction influences the pH-dependence of pore formation; and how the pore functions in promoting translocation of LF andEF across the endosomal membrane.
Journal ArticleDOI
Macrophages are sensitive to anthrax lethal toxin through an acid-dependent process.
TL;DR: It is suggested that anthrax lethal toxin requires passage through an acidic endocytic vesicle in order to exert its toxic effect within the cytosol.
References
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Journal Article
The Chemical Basis of the Virulence of Bacillus anthracis. V. The Specific Toxin produced by B. anthracis in vivo.
H. Smith,J. Keppie,J. L. Stanley +2 more
Journal Article
The chemical basis of the virulence of bacillus anthracis. ix. its aggressins and their mode of action.
Journal ArticleDOI
The Three Factors of Anthrax Toxin: their Immunogenicity and Lack of Demonstrable Enzymic Activity
J. L. Stanley,H. Smith +1 more
TL;DR: A lethal mixture of the three factors (I, II, III) of anthrax toxin had none of the following enzyme activities: adenosine triphosphatase, alkaline or acid phosphatases, catalase, collagenase, ribonuclease, gelatinase, hyaluronidase, lecithinase, lipase, proteinase.
Journal ArticleDOI
ISOLATION OF ADENYL CYCLASE FROM Escherichia coli
Mariano Tao,Fritz Lipmann +1 more
TL;DR: A soluble cyclase is found using for assay radioactively marked ATP as precursor and has a Mg(++) requirement and is inhibited by fluoride and inorganic pyrophosphate.
Journal ArticleDOI
Isolation of multiple classes of mutants of CHO cells resistant to cyclic AMP
TL;DR: From mutagenized Chinese hamster ovary (CHO) cells, 11 independent mutants resistant to the growthinhibitory effects of 8-Brcyclic AMP, cholera toxin, and methylisobutylxanthine are isolated.