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

Joanna C. Young, Abigail Clements, Alexander E. Lang, James A. Garnett, Diana Munera, Ana Arbeloa, Jaclyn Pearson, Elizabeth L. Hartland, Stephen J. Matthews, Aurelie Mousnier, David J. Barry, Michael Way, Andreas Schlosser, Klaus Aktories and Gad Frankel ()
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Joanna C. Young: MRC Centre for Molecular Bacteriology and Infection, Imperial College
Abigail Clements: MRC Centre for Molecular Bacteriology and Infection, Imperial College
Alexander E. Lang: Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg
James A. Garnett: Centre for Structural Biology, Imperial College
Diana Munera: MRC Centre for Molecular Bacteriology and Infection, Imperial College
Ana Arbeloa: MRC Centre for Molecular Bacteriology and Infection, Imperial College
Jaclyn Pearson: University of Melbourne, at the Peter Doherty Institute for Infection and Immunity
Elizabeth L. Hartland: University of Melbourne, at the Peter Doherty Institute for Infection and Immunity
Stephen J. Matthews: Centre for Structural Biology, Imperial College
Aurelie Mousnier: MRC Centre for Molecular Bacteriology and Infection, Imperial College
David J. Barry: Cell Motility Laboratory, Cancer Research UK, London Research Institute
Michael Way: Cell Motility Laboratory, Cancer Research UK, London Research Institute
Andreas Schlosser: Rudolf Virchow Center for Experimental Biomedicine, University of Wuerzburg
Klaus Aktories: Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg
Gad Frankel: MRC Centre for Molecular Bacteriology and Infection, Imperial College

Nature Communications, 2014, vol. 5, issue 1, 1-10

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms6887

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