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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Functional aspects of the Leishmania donovani lipophosphoglycan during macrophage infection.
TL;DR: The most abundant surface glycoconjugate of the Leishmania promastigotes is lipophosphoglycan, a glycosylphosphatidyl-inositol-anchored polymer of the repeating disaccharide-phosphate Gal(beta1,4)Manalpha1-PO4 unit.
Journal ArticleDOI
Anthrax Toxins Inhibit Neutrophil Signaling Pathways in Brain Endothelium and Contribute to the Pathogenesis of Meningitis
Nina M. van Sorge,Celia M. Ebrahimi,Shauna M. McGillivray,Darin Quach,Mojgan Sabet,Donald G. Guiney,Kelly S. Doran,Kelly S. Doran +7 more
TL;DR: A significant role is suggested for anthrax toxins in thwarting the BBB innate defense response promoting penetration of bacteria into the central nervous system.
Journal ArticleDOI
Late treatment with a protective antigen-directed monoclonal antibody improves hemodynamic function and survival in a lethal toxin-infused rat model of anthrax sepsis.
Xizhong Cui,Yan Li,Mahtab Moayeri,Gil H. Choi,G. M. Subramanian,Xuemei Li,Michael Haley,Yvonne Fitz,Jing Feng,Steven M. Banks,Stephen H. Leppla,Peter Q. Eichacker +11 more
TL;DR: Clinically, PA-MAb may be beneficial even when administered after the onset of shock and lethality due to LeTx, and improvements in outcome were significant when it was administered up to 6 h (and approached significance when administeredup to 12 h) after initial exposure to Letx.
Journal ArticleDOI
MEK genomics in development and disease
TL;DR: This review will discuss recent advances in the discovery of genomic variants in MEK1 and MEK2, relating them to what is currently understood about the structure and function of MEKs, and describe how they change the authors' understanding of the role ofMEKs in development and disease.
Journal ArticleDOI
Targeting Bacterial Toxins
TL;DR: The discussion focuses on A-B-type protein toxins secreted by four species of bacteria, namely Clostridium difficile, Vibrio cholerae, enterohemorrhagic Escherichia coli, Shiga toxin, and Bacillus anthracis, which are the causative agents of diseases for which treatments need to be improved.
References
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A synthetic inhibitor of the mitogen-activated protein kinase cascade.
TL;DR: Results indicate that the MAPK pathway is essential for growth and maintenance of the ras-transformed phenotype and PD 098059 is an invaluable tool that will help elucidate the role of theMAPK cascade in a variety of biological settings.
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Cyclin is degraded by the ubiquitin pathway
TL;DR: Cyclin degradation is the key step governing exit from mitosis and progress into the next cell cycle, and anaphase may be triggered by the recognition of cyclin by the ubiquitin-conjugating system.
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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
TL;DR: It is found that constitutive activation of MAPKK is sufficient to promote cell transformation and is associated with highly tumorigenic in nude mice.
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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.