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
Soluble expression and purification of the anthrax protective antigen in E. coli and identification of a novel dominant-negative mutant N435C
TL;DR: The solubility of recombinant PA was dramatically enhanced by fusion with glutathione S-transferase (GST) and an induction of its expression at 28°C, and a novel mutant N435C which conferred dominant-negative inhibitory activity on PA was identified, useful in designing new antitoxin for anthrax prophylaxis and therapy.
Journal ArticleDOI
Hydrophobic residues Phe552, Phe554, Ile562, Leu566, and Ile574 are required for oligomerization of anthrax protective antigen.
TL;DR: Hydrophobic residues, Phe552, P he554, Ile562, Leu566, and Ile574, which are required for oligomerization of anthrax protective antigen are identified and their potential as vaccine candidates is discussed.
Journal ArticleDOI
Bacillus anthracis Edema Factor Substrate Specificity: Evidence for New Modes of Action
TL;DR: This review discusses the broad EF substrate specificity and possible implications of intracellular accumulation of cyclic cytidine 3′:5′-monophosphate, cyclic uridine 5′-triphosphate and cyclic inosine 3′-Monophosphates on cellular functions vital for host defense.
Journal ArticleDOI
Evaluation of combinatorial vaccines against anthrax and plague in a murine model.
TL;DR: A combinatorial vaccine consisting of equal amounts of F1-V and rPA administered SC is effective at eliciting a robust serum and bronchoalveolar lavage antigen- specific IgG and IgG1 response against both antigens in immunized animals, and when administered IN, a robust antigen-specific IgG2a response in the serum and BAL is also induced.
Book ChapterDOI
Host Signal Transduction and Protein Kinases Implicated in Legionella Infection
TL;DR: Modulation of the phosphorylation status of proteins by both kinases and phosphatases plays an important role in cellular signal transduction and proper regulation of host cell signaling by L. pneumophila is necessary for its ability to replicate intracellulary, while avoiding host defenses.
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.