Bacterial and Host Determinants of MAL Activation upon EPEC Infection: The Roles of Tir, ABRA, and FLRT3

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Bacterial and Host Determinants of MAL Activation upon EPEC Infection: The Roles of Tir, ABRA, and FLRT3

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dc.contributor.author Leong, John M.
dc.contributor.author Machesky, Laura M.
dc.contributor.author Heath, Robert John William
dc.contributor.author Xavier, Ramnik
dc.contributor.author Visegrády, Balázs
dc.date.accessioned 2012-01-03T04:42:32Z
dc.date.issued 2011
dc.identifier.citation Heath, Robert J. W., John M. Leong, Balázs Visegrády, Laura M. Machesky, and Ramnik J. Xavier. 2011. Bacterial and host determinants of MAL activation upon EPEC infection: The roles of Tir, ABRA, and FLRT3. PLoS Pathogens 7(4): e1001332. en_US
dc.identifier.issn 1553-7366 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:5978758
dc.description.abstract Infection of host cells by pathogenic microbes triggers signal transduction pathways leading to a multitude of host cell responses including actin cytoskeletal re-arrangements and transcriptional programs. The diarrheagenic pathogens Enteropathogenic E. coli (EPEC) and the related Enterohemorrhagic E. coli (EHEC) subvert the host-cell actin cytoskeleton to form attaching and effacing lesions on the surface of intestinal epithelial cells by injecting effector proteins via a type III secretion system. Here we use a MAL translocation assay to establish the effect of bacterial pathogens on host cell signaling to transcription factor activation. MAL is a cofactor of Serum response factor (SRF), a transcription factor with important roles in the regulation of the actin cytoskeleton. We show that EPEC induces nuclear accumulation of MAL-GFP. The translocated intimin receptor is essential for this process and phosphorylation of Tyrosine residues 454 and 474 is important. Using an expression screen we identify FLRT3, C22orf28 and TESK1 as novel activators of SRF. Importantly we demonstrate that ABRA (actin-binding Rho-activating protein, also known as STARS) is necessary for EPEC-induced nuclear accumulation of MAL and the novel SRF activator FLRT3, is a component of this pathway. We further demonstrate that ABRA is important for structural maintenance of EPEC pedestals. Our results uncover novel components in pathogen-activated cytoskeleton signalling to MAL activation. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.ppat.1001332 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3072376/pdf/ en_US
dash.license LAA
dc.subject cell biology en_US
dc.subject cytoskeleton en_US
dc.subject cellular microbiology and pathogenesis en_US
dc.subject transcription initiation and activation en_US
dc.title Bacterial and Host Determinants of MAL Activation upon EPEC Infection: The Roles of Tir, ABRA, and FLRT3 en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS Pathogens en_US
dash.depositing.author Xavier, Ramnik
dc.date.available 2012-01-03T04:42:32Z
dash.affiliation.other HMS^Medicine-Massachusetts General Hospital en_US

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