Shigella flexneri type III secreted effector OspF reveals new crosstalks of proinflammatory signaling pathways during bacterial infection
| Autor: | Christoph Kasper, Lars Grossniklaus, Therese Tschon, Cécile Arrieumerlou, Veronika Reiterer, Isabel Sorg |
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| Rok vydání: | 2011 |
| Předmět: |
MAPK/ERK pathway
Phosphorylases Transcription Genetic p38 mitogen-activated protein kinases Biology p38 Mitogen-Activated Protein Kinases Cell Line Shigella flexneri Microbiology Mice 03 medical and health sciences Bacterial Proteins Animals Humans Phosphorylation Transcription factor Dysentery Bacillary 030304 developmental biology Feedback Physiological Inflammation 0303 health sciences Tumor Necrosis Factor-alpha Effector 030302 biochemistry & molecular biology JNK Mitogen-Activated Protein Kinases Transcription Factor RelA Cell Biology biology.organism_classification Recombinant Proteins 3. Good health Enzyme Activation Phosphothreonine lyase activity Inflammation Mediators Signal transduction Signal Transduction |
| Zdroj: | Cellular signalling |
| DOI: | 10.1016/j.cellsig.2011.03.006 |
| Popis: | Shigella flexneri type III secreted effector OspF harbors a phosphothreonine lyase activity that irreversibly dephosphorylates MAP kinases (MAPKs) p38 and ERK in infected epithelial cells and thereby, dampens innate immunity. Whereas this activity has been well characterized, the impact of OspF on other host signaling pathways that control inflammation was unknown. Here we report that OspF potentiates the activation of the MAPK JNK and the transcription factor NF-κB during S. flexneri infection. This unexpected effect of OspF was dependent on the phosphothreonine lyase activity of OspF on p38, and resulted from the disruption of a negative feedback loop regulation between p38 and TGF-beta activated kinase 1 (TAK1), mediated via the phosphorylation of TAK1-binding protein 1. Interestingly, potentiated JNK activation was not associated with enhanced c-Jun signaling as OspF also inhibits c-Jun expression at the transcriptional level. Altogether, our data reveal the impact of OspF on the activation of NF-κB, JNK and c-Jun, and demonstrate the existence of a negative feedback loop regulation between p38 and TAK1 during S. flexneri infection. Furthermore, this study validates the use of bacterial effectors as molecular tools to identify the crosstalks that connect important host signaling pathways induced upon bacterial infection. |
| Databáze: | OpenAIRE |
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