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
Protection against anthrax lethal toxin challenge by genetic immunization with a plasmid encoding the lethal factor protein.
Brian M. Price,Adriane L. Liner,Sukjoon Park,Stephen H. Leppla,Alfred Mateczun,Darrell R. Galloway +5 more
TL;DR: It is demonstrated that DNA-based immunization alone can provide protection against a lethal toxin challenge and that DNA immunization against the LF antigen alone provides complete protection.
Journal ArticleDOI
The bacterial toxin toolkit
TL;DR: Pathogenic bacteria and higher eukaryotes have spent a long time together, leading to a precise understanding of one another's way of functioning, and have become an essential asset for life scientists, who can now use them as toolkits to explore cellular processes.
Journal ArticleDOI
Capillary morphogenesis protein-2 is the major receptor mediating lethality of anthrax toxin in vivo.
Shihui Liu,Devorah Crown,Sharmina Miller-Randolph,Mahtab Moayeri,Hailun Wang,Haijing Hu,T. D. Morley,Stephen H. Leppla +7 more
TL;DR: It is found that the lethality of anthrax toxin for mice is mostly mediated by CMG2 and that TEM8 plays only a minor role, attesting to the importance of both anthrax toxins andCMG2 in anthrax infections.
Journal ArticleDOI
Anthrax lethal toxin induces endothelial barrier dysfunction.
TL;DR: A possible role for LT-induced barrier dysfunction in the vascular permeability changes accompanying systemic anthrax infection is supported and is not dependent on endothelial apoptosis or necrosis.
Journal ArticleDOI
Targeting Metalloenzymes for Therapeutic Intervention
Allie Y. Chen,Rebecca N Adamek,Benjamin L. Dick,Cy V. Credille,Christine N. Morrison,Seth M. Cohen +5 more
TL;DR: This Review provides a broad overview of several drug discovery efforts focused on metalloenzymes and attempts to map out the current landscape of high-value metaloenzyme targets.
References
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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.