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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Journal Article
Aerosolized Bacillus anthracis infection in New Zealand white rabbits: natural history and intravenous levofloxacin treatment.
TL;DR: Results suggest that intravenous levofloxacin is an effective therapeutic against inhalational anthrax and indicate that antigenemia is a viable and early biomarker for B. anthracis infection that can be used as a treatment trigger to allow for timely intervention against this highly pathogenic disease.
Journal ArticleDOI
Cytokine response and survival of mice immunized with an adenovirus expressing Bacillus anthracis protective antigen domain 4.
TL;DR: It is demonstrated that interleukin 1β (IL-1β) levels in mice that survive lethal toxin challenge are similar to levels in nonsurvivors and that IL-6 levels are higher in survivors than in non-survivors, suggesting that lethal-toxin-mediated death may not be a direct result of inflammatory-cytokine release.
Journal ArticleDOI
Effects of dynamin inactivation on pathways of anthrax toxin uptake.
TL;DR: DTA, a surrogate of LF consisting of the N-terminal domain of LF fused to the catalytic subunit of diphtheria toxin, is used to differentiate the effects of acute and long-term block of dynamin function on LFn-DTA toxicity.
BookDOI
Electrophysiology of Unconventional Channels and Pores
TL;DR: The discussed biophysical insights of VDAC blockage by tubulin, obtained from experiments at the single-molecule level, could be also important for understanding the molecular mechanisms of functional interactions between water soluble and membrane proteins in general.
Journal ArticleDOI
Effects of spontaneous deamidation on the cytotoxic activity of the Bacillus anthracis protective antigen.
TL;DR: It is suggested that PA inactivation during storage is associated with susceptible deamidation sites, which are intimately involved in both mechanisms of PA cleavage by furin and PA-receptor binding.
References
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Transformation of mammalian cells by constitutively active MAP kinase kinase
Sam J. Mansour,W. T. Matten,April S. Hermann,Julian M. Candia,Sing Rong,Kenji Fukasawa,G F Vande Woude,Natalie G. Ahn +7 more
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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
Multiple Ras functions can contribute to mammalian cell transformation.
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.