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Nat Commun. 2014 Dec 19;5:5887. doi: 10.1038/ncomms6887.

The Escherichia coli effector EspJ blocks Src kinase activity via amidation and ADP ribosylation.

Author information

1
MRC Centre for Molecular Bacteriology and Infection, Imperial College, SW7 2AZ London, UK.
2
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, D-79104 Freiburg, Germany.
3
Centre for Structural Biology, Imperial College, SW7 2AZ London, UK.
4
Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne Victoria 3010, Australia.
5
Cell Motility Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
6
Rudolf Virchow Center for Experimental Biomedicine, University of Wuerzburg, 97080 Würzburg, Germany.
7
1] Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, D-79104 Freiburg, Germany [2] Centre for Biological Signalling Studies (BIOSS), University of Freiburg, D-79104 Freiburg, Germany.

Abstract

The hallmark of enteropathogenic Escherichia coli (EPEC) infection is the formation of actin-rich pedestal-like structures, which are generated following phosphorylation of the bacterial effector Tir by cellular Src and Abl family tyrosine kinases. This leads to recruitment of the Nck-WIP-N-WASP complex that triggers Arp2/3-dependent actin polymerization in the host cell. The same phosphorylation-mediated signalling network is also assembled downstream of the Vaccinia virus protein A36 and the phagocytic Fc-gamma receptor FcγRIIa. Here we report that the EPEC type-III secretion system effector EspJ inhibits autophosphorylation of Src and phosphorylation of the Src substrates Tir and FcγRIIa. Consistent with this, EspJ inhibits actin polymerization downstream of EPEC, Vaccinia virus and opsonized red blood cells. We identify EspJ as a unique adenosine diphosphate (ADP) ribosyltransferase that directly inhibits Src kinase by simultaneous amidation and ADP ribosylation of the conserved kinase-domain residue, Src E310, resulting in glutamine-ADP ribose.

PMID:
25523213
PMCID:
PMC4284639
DOI:
10.1038/ncomms6887
[Indexed for MEDLINE]
Free PMC Article

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