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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / genetics
  • Adenosine Diphosphate / metabolism*
  • Amino Acid Motifs
  • Enterohemorrhagic Escherichia coli / genetics
  • Enterohemorrhagic Escherichia coli / metabolism*
  • Escherichia coli Infections / enzymology*
  • Escherichia coli Infections / genetics
  • Escherichia coli Infections / metabolism
  • Escherichia coli Infections / microbiology
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Humans
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Receptors, IgG / metabolism
  • src-Family Kinases / chemistry
  • src-Family Kinases / genetics
  • src-Family Kinases / metabolism*

Substances

  • Escherichia coli Proteins
  • EspJ protein, E coli
  • Fc gamma receptor IIA
  • Receptors, IgG
  • Adenosine Diphosphate
  • src-Family Kinases