Journal ArticleDOI
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
TLDR
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.Abstract:
Anthrax lethal toxin, produced by the bacterium Bacillus anthracis, is the major cause of death in animals infected with anthrax. One component of this toxin, lethal factor (LF), is suspected to be a metalloprotease, but no physiological substrates have been identified. Here it is shown that LF is a protease that cleaves the amino terminus of mitogen-activated protein kinase kinases 1 and 2 (MAPKK1 and MAPKK2) and that this cleavage inactivates MAPKK1 and inhibits the MAPK signal transduction pathway. The identification of a cleavage site for LF may facilitate the development of LF inhibitors.read more
Citations
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Patent
Method for delivering agents into cells using bacterial toxins
TL;DR: In this article, the authors provide compositions and methods for delivering a bioactive moiety comprising at least one non-natural component into a cell cytosol of an eukaryotic cell.
Journal ArticleDOI
Bacillus anthracis lethal toxin negatively modulates ILC3 function through perturbation of IL-23-mediated MAPK signaling.
Sudarshan Seshadri,David S.J. Allan,David S.J. Allan,James R. Carlyle,James R. Carlyle,Lauren A. Zenewicz +5 more
TL;DR: This work found that B. anthracis lethal toxin perturbed ILC3 function in vitro and in vivo, revealing an unknown IL-23-mediated MAPK signaling pathway and may lead to new approaches for targeting IL-22 biology.
Journal ArticleDOI
Anthrax Lethal Factor Investigated by Molecular Simulations.
TL;DR: These calculations suggest that the presence of second-shell ligands is crucial for tuning the structure, energetics, and protonation state of the metal binding site of the anthrax Lethal Factor using several computational methods including density functional theory, molecular dynamics, and coarse grained techniques.
Book ChapterDOI
Uptake of Protein Toxins Acting Inside Cells
TL;DR: An increasing number of bacterial protein toxins are being demonstrated to have intracellular sites of action, which implies that the toxins must be able to cross cellular membranes.
Journal ArticleDOI
The Salmonella effector AvrA mediates bacterial intracellular survival during infection
TL;DR: It is demonstrated that Salmonella AvrA modulates survival of infected macrophages likely via JNK suppression, and prevents macrophage death and rapid bacterial dissemination.
References
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Journal ArticleDOI
Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells.
TL;DR: 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.
Journal ArticleDOI
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Michael A. White,Charles Nicolette,Audrey Minden,Anthony Polverino,Linda Van Aelst,Michael Karin,Michael Wigler +6 more
TL;DR: Results indicate that multiple cellular components, including Raf1, are activated by Ha-Ras and contribute to Ha- Ras-induced mammalian cell transformation.