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@article{Pollard:2018:10.1128/mBio.00170-18,
author = {Pollard, D and Berger, CN and So, E and Yu, L and Hadavizadeh, K and Jennings, P and Tate, E and Choudhary, J and Frankel, G},
doi = {10.1128/mBio.00170-18},
journal = {mBio},
title = {Broad spectrum regulation of non receptor tyrosine kinases by the bacterial ADP ribosyltransferase EspJ},
url = {http://dx.doi.org/10.1128/mBio.00170-18},
volume = {9},
year = {2018}
}
TY - JOUR
AB - Tyrosine phosphorylation is key for signal transduction fromexogenousstimuli, including the defence against pathogens. Conversely, pathogens cansubvert protein phosphorylation to control hostimmune responsesand facilitateinvasionanddissemination. The bacterial 23effectorsEspJand SeoC areinjected into host cellsthough a type III secretion system by enteropathogenic and enterohaemorrhagic Escherichia coli(EPEC and EHEC), Citrobacter rodentiumand Salmonellaentericawhere they inhibit Src kinase bycoupledamidation andADP-ribosylation. C. rodentium, which is used tomodel EPEC and EHEC infections in human, is a mouse pathogen triggeringcolonic crypt hyperplasia (CCH) and colitis. Enumeration of bacterial shedding and CCH confirmed that EspJ affects neither tolerance nor resistance to infection. However, comparing the proteomes of intestinal epithelial cells isolated from mice infected with wildtype C.rodentiumor C. rodentiumencoding catalyticallyinactive EspJrevealed that EspJ-induced ADP-ribosylationregulatesmultiple non-receptor tyrosine kinasesin vivo. Investigating the substrate repertoire of EspJ revealed that in HeLa and A549 Src and Csk were significantly targeted; in polarised Caco2 cells EspJ targeted Src and Csk and the Src family kinase (SFK) Yes1, while in differentiated Thp1 EspJ modifiedCsk, the SFKs Hck and Lyn, the Tec family kinases Tec and Btk, and the adapter tyrosine kinase Syk. Furthermore, Abl (HeLa and Caco2) and Lyn (Caco2) were enriched specifically in the EspJ-containing samples. Biochemical assays revealed that EspJ, the only bacterial ADP-ribosyltransferase which targets mammalian kinases,controls immune responses andthe Src/Csk signalling axis.
AU - Pollard,D
AU - Berger,CN
AU - So,E
AU - Yu,L
AU - Hadavizadeh,K
AU - Jennings,P
AU - Tate,E
AU - Choudhary,J
AU - Frankel,G
DO - 10.1128/mBio.00170-18
PY - 2018///
SN - 2150-7511
TI - Broad spectrum regulation of non receptor tyrosine kinases by the bacterial ADP ribosyltransferase EspJ
T2 - mBio
UR - http://dx.doi.org/10.1128/mBio.00170-18
UR - http://hdl.handle.net/10044/1/57875
VL - 9
ER -
Prof. Ed Tate
GSK Chair in Chemical Biology
Department of Chemistry
Molecular Sciences Research Hub, White City Campus,
82 Wood Lane, London, W12 0BZ
e.tate@imperial.ac.uk
Tel: +44 (0)20 759 + ext 43752 or 45821