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

Author

Listed:
  • 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
    Centre for Biological Signalling Studies (BIOSS), University of Freiburg)

  • Gad Frankel

    (MRC Centre for Molecular Bacteriology and Infection, Imperial College)

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.

Suggested Citation

  • 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. Barr, 2014. "The Escherichia coli effector EspJ blocks Src kinase activity via amidation and ADP ribosylation," Nature Communications, Nature, vol. 5(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6887
    DOI: 10.1038/ncomms6887
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