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
Delivery of Non-Native Cargo into Mammalian Cells Using Anthrax Lethal Toxin
TL;DR: Insight into design parameters for the efficient delivery of new cargos using PA and LFN is provided and it is demonstrated that non-native cargo must adopt an unfolded or extended conformation and contain a suitable charge composition in order to efficiently pass through the PA pore.
Journal ArticleDOI
Anthrax oedema toxin induces anthrax toxin receptor expression in monocyte‐derived cells
TL;DR: It is demonstrated that oedema toxin (PA’+ OF) induces an increase in ANTXR expression levels in macrophages and dendritic cells resulting in an increased rate of toxin internalization, the first report of a bacterial toxin inducing host target cells to increase toxin receptor expression.
Journal ArticleDOI
Quantitative Mass Spectrometry for Bacterial Protein Toxins — A Sensitive, Specific, High-Throughput Tool for Detection and Diagnosis
Anne E. Boyer,Maribel Gallegos-Candela,Renato C. Lins,Zsuzsanna Kuklenyik,Adrian R. Woolfitt,Hercules Moura,Suzanne R. Kalb,Conrad P. Quinn,John R. Barr +8 more
TL;DR: These combined technologies have achieved high specificity, ultrasensitive detection and quantification of the anthrax toxins and potential applications to diseases of high public health impact, including Clostridium difficile glucosylating toxins and the Bordetella pertussis adenylyl cyclase.
Journal ArticleDOI
Characterization of the interaction between anthrax toxin and its cellular receptors
TL;DR: It is demonstrated that CMG2 proteins with certain JHF‐ and ISH‐associated single amino acid substitutions in their von Willebrand factor A domain or transmembrane region do not function as anthrax toxin receptors, and an ISH •CMG2 variant having a truncated cytosolic domain does still function as an anthrax receptor.
Journal ArticleDOI
Changing the Receptor Specificity of Anthrax Toxin
TL;DR: Results show that the receptor specificity of the transport protein of anthrax toxin may be readily changed, raising the possibility that receptor-redirected forms of protective antigen (PA) and PA homologs may be useful for research and medical applications requiring modification or ablation of designated populations of cells.
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
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.