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 ArticleDOI
Immunization of mice with formalin-inactivated spores from avirulent Bacillus cereus strains provides significant protection from challenge with Bacillus anthracis Ames.
James M. Vergis,Christopher K. Cote,Joel A. Bozue,Farhang Alem,Christy L. Ventura,Susan L. Welkos,Alison D. O'Brien +6 more
TL;DR: Overall the data show that immunization with FIS from nontoxigenic, nonencapsulated B. cereus strains provides moderate to high levels of protection of mice from B. anthracis Ames challenge and that neither PA nor BclA is required for this protection.
Journal ArticleDOI
Production and proteolytic assay of lethal factor from Bacillus anthracis
TL;DR: This study constructed and produced rLF as a form of GST fusion protein in Escherichia coli and developed an in vitro immobilized proteolytic assay of LF under the condition containing full-length native substrate, MEK1, rather than short synthetic peptide.
Patent
Marine actinomycete taxon for drug and fermentation product discovery
TL;DR: Salinospora gen. nov as mentioned in this paper is a genus of actinomycete that displays an obligate requirement of seawater (Na + ) for growth and unique 16S rRNA signature nucleotides.
Journal ArticleDOI
Identification of novel host-targeted compounds that protect from anthrax lethal toxin-induced cell death.
Louise H. Slater,Erik C. Hett,Erik C. Hett,Kevin G. Mark,Kevin G. Mark,Nicole M. Chumbler,Deepa Patel,D. Borden Lacy,R. John Collier,Deborah T. Hung,Deborah T. Hung +10 more
TL;DR: A phenotypic small molecule screen was conducted to identify inhibitors of lethal toxin-induced macrophage cell death and used an ordered series of secondary assays to characterize the hits and determine their effects on cellular function.
References
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Transformation of mammalian cells by constitutively active MAP kinase kinase
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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.