Exceptionally Selective Substrate Targeting by the Metalloprotease Anthrax Lethal Factor

Turk, Benjamin E.

doi:10.1007/5584_2018_273

Cited by 4 publications

(2 citation statements)

References 80 publications

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“…A well-characterized example is that of the Lethal Factor, a component of the anthrax toxin that is secreted by Bacillus anthracis, and that possesses highly selective endopeptidase activity directed against host cell MEKs, thereby inactivating MAPK pathways (reviewed in ref. 55 ). Downregulation of MAPK pathways through degradation of specific components is not restricted to host-pathogen interactions.…”

Section: Discussionmentioning

confidence: 99%

Analysis of erythrocyte signalling pathways during Plasmodium falciparum infection identifies targets for host-directed antimalarial intervention

et al. 2020

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Intracellular pathogens mobilize host signaling pathways of their host cell to promote their own survival. Evidence is emerging that signal transduction elements are activated in anucleated erythrocytes in response to infection with malaria parasites, but the extent of this phenomenon remains unknown. Here, we fill this knowledge gap through a comprehensive and dynamic assessment of host erythrocyte signaling during infection with Plasmodium falciparum. We used arrays of 878 antibodies directed against human signaling proteins to interrogate the activation status of host erythrocyte phospho-signaling pathways at three blood stages of parasite asexual development. This analysis reveals a dynamic modulation of many host signalling proteins across parasite development. Here we focus on the hepatocyte growth factor receptor (c-MET) and the MAP kinase pathway component B-Raf, providing a proof of concept that human signaling kinases identified as activated by malaria infection represent attractive targets for antimalarial intervention.

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Section: Discussionmentioning

confidence: 99%

Analysis of erythrocyte signalling pathways during Plasmodium falciparum infection identifies targets for host-directed antimalarial intervention

et al. 2020

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“…This is reminiscent of the strategy of other intracellular pathogen to modify the composition of signaling pathways in their host cell. A well-characterised example is that of the Lethal Factor, a component of the anthrax toxin that is secreted by Bacillus anthracis and that possesses highly selective endopeptidase activity directed against host cell MEKs, thereby inactivating MAPK pathways (reviewed in 60 ). Down-regulation of MAPK pathways through degradation of specific components is not restricted to host-pathogen interactions.…”

Section: Discussionmentioning

confidence: 99%