Exoenzyme S of Pseudomonas aeruginosa is not able to induce apoptosis when cells express activated proteins, such as Ras or protein kinase B/Akt
| Autor: | Ruth H. Palmer, Lubna Yasmin, Anna L. Jansson, Bengt Hallberg, Patricia H. Warne, Julian Downward |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Programmed cell death
Bacterial Toxins Immunology Apoptosis macromolecular substances Biology Mitogen-activated protein kinase kinase Microbiology Mice Dogs Phagocytosis Virology Animals c-Raf Phosphorylation Protein kinase B ADP Ribose Transferases Caspase 3 Akt/PKB signaling pathway Forkhead Box Protein O3 fungi Forkhead Transcription Factors Cell biology Enzyme Activation Proto-Oncogene Proteins c-raf carbohydrates (lipids) enzymes and coenzymes (carbohydrates) Yersinia pseudotuberculosis Cell culture Caspases Pseudomonas aeruginosa NIH 3T3 Cells ras Proteins Signal transduction Proto-Oncogene Proteins c-akt Intracellular Signal Transduction |
| Zdroj: | Cellular Microbiology. 8:815-822 |
| ISSN: | 1462-5822 1462-5814 |
| DOI: | 10.1111/j.1462-5822.2005.00668.x |
| Popis: | Intracellular targeting of the Pseudomonas aeruginosa toxins, such as exoenzyme S (ExoS), cause cell death, as well as morphological and physiological changes in various tissue culture cells and animal models. In this report we have investigated the mechanism behind ExoS-mediated cell death. In order to address this issue, we have used cell lines expressing activated forms of various components of the Ras signalling pathway in order to evaluate the importance of the Ras pathway for viability and survival upon ExoS infection. Here we show that activated Ras is able to protect cells against cell death, regardless of whether it has been ADP-ribosylated by ExoS. Further, an activated form of protein kinase B (PKB)/Akt also leads to decreased level of cell death in response to ExoS infection, indicating that an important ExoS survival target is located upstream of Raf-1 and PKB/Akt. Moreover, we show that ExoS infection inhibits phosphorylation of FOXO3a, and induces caspase-3 activity, which are hallmarks for induction of cell death. In conclusion, we suggest that Ras proteins are an important cellular target for the P. aeruginosa toxin ExoS, which induces cell death during pathogenesis as a means of defending the bacterium against eukaryotic phagocytosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|