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Systems-level overview of host protein phosphorylation during Shigella flexneri infection revealed by phosphoproteomics

Schmutz, Christoph and Ahrne, Erik Lennart and Kasper, Christoph Alexander and Tschon, Therese and Sorg, Isabel and Dreier, Roland Felix and Schmidt, Alexander and Arrieumerlou, Cecile. (2013) Systems-level overview of host protein phosphorylation during Shigella flexneri infection revealed by phosphoproteomics. Molecular & cellular proteomics, Vol. 12, H. 10. pp. 2952-2968.

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Official URL: http://edoc.unibas.ch/dok/A6164920

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Abstract

The enteroinvasive bacterium Shigella flexneri invades the intestinal epithelium of humans. During infection, several injected effector proteins promote bacterial internalization, and interfere with multiple host cell responses. To obtain a systems-level overview of host signaling during infection, we analyzed the global dynamics of protein phosphorylation by LC-MS/MS and identified several hundred of proteins undergoing a phosphorylation change during the first hours of infection. Functional bioinformatic analysis revealed that they were mostly related to the cytoskeleton, transcription, signal transduction, and cell cycle. Fuzzy c-means clustering identified six temporal profiles of phosphorylation and a functional module composed of ATM-phosphorylated proteins related to genotoxic stress. Pathway enrichment analysis defined mTOR as the most overrepresented pathway. We showed that mTOR complex 1 and 2 were required for S6 kinase and AKT activation, respectively. Comparison with a published phosphoproteome of Salmonella typhimurium-infected cells revealed a large subset of co-regulated phosphoproteins. Finally, we showed that S. flexneri effector OspF affected the phosphorylation of several hundred proteins, thereby demonstrating the wide-reaching impact of a single bacterial effector on the host signaling network.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Molecular Microbiology (Arrieumerlou)
UniBasel Contributors:Arrieumerlou, Cécile and Schmutz, Christoph and Ahrné, Erik and Kasper, Christoph and Tschon, Therese and Sorg, Isabel and Dreier, Roland and Schmidt, Alexander
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:The American Society for Biochemistry and Molecular Biology
ISSN:1535-9484
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:25 Oct 2013 08:33
Deposited On:25 Oct 2013 08:33

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