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
The development of new vaccines against Bacillus anthracis
TL;DR: This paper will give a brief overview of the organism, its pathogenicity and the efforts being made to develop new vaccines.
Journal ArticleDOI
Enhancement of Anthrax Lethal Toxin Cytotoxicity: a Subset of Monoclonal Antibodies against Protective Antigen Increases Lethal Toxin-Mediated Killing of Murine Macrophages
Nehal Mohamed,Juan Li,Claudia S. Ferreira,Stephen F. Little,Arthur M. Friedlander,George L. Spitalny,Leslie S. Casey +6 more
TL;DR: An overlooked population of anti-PA MAbs are described for the first time that function to increase the potency of LeTx against murine macrophage cell lines and support a possible mechanism of enhancement.
Journal ArticleDOI
Bacillus anthracis edema and lethal toxin have different hemodynamic effects but function together to worsen shock and outcome in a rat model.
Xizhong Cui,Yan Li,Xuemei Li,Michael W. Laird,Mani Subramanian,Mahtab Moayeri,Stephen H. Leppla,Yvonne Fitz,Junwu Su,Kevin Sherer,Peter Q. Eichacker +10 more
TL;DR: ETx was approximately 10 times less lethal than LeTx but produced greater hypotension and added to the latter's harmful effects, suggesting that it may be appropriate for antitoxin therapies for B. anthracis to target both ETx and LeTx.
Journal ArticleDOI
Role of the protective antigen octamer in the molecular mechanism of anthrax lethal toxin stabilization in plasma
Alexander F. Kintzer,Harry J. Sterling,Iok I. Tang,Ali Abdul-Gader,Andrew J. Miles,Bonnie A. Wallace,Evan R. Williams,Bryan A. Krantz +7 more
TL;DR: It is concluded that PA may form an octameric oligomeric state as a means to produce a more stable and active LT complex that could circulate freely in the blood.
Journal ArticleDOI
Growth inhibition of breast cancer cells by Grb2 downregulation is correlated with inactivation of mitogen-activated protein kinase in EGFR, but not in ErbB2, cells.
TL;DR: Liposomes are used to deliver nuclease-resistant antisense oligodeoxynucleotides specific for the GRB2 mRNA to breast cancer cells to inhibit breast cancer cell growth and suggest different pathways might be used by EGFR and ErbB2 to regulate breast cancer growth.
References
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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.