Protein abundance comparison of human cells infected with Shigella flexneri over different time periods
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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 (PMID:21934108, PRIDE experiment accessions 18477 and 18485) 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.
INSTRUMENT(S): LTQ Orbitrap, instrument model
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Permanent Cell Line Cell, Cell Culture
SUBMITTER: Alexander Schmidt
LAB HEAD: Alexander Schmidt
PROVIDER: PXD000219 | Pride | 2017-01-23
REPOSITORIES: Pride
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