Enteropathogenic Escherichia coli dynamically regulates EGFR signaling in intestinal epithelial cells

Jennifer Lising Roxas, Katheryn Ryan, Gayatri Vedantam, V. K. Viswanathan

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

The diarrheagenic pathogen enteropathogenic Escherichia coli (EPEC) dynamically modulates the survival of infected host intestinal epithelial cells. In the initial stages of infection, several prosurvival signaling events are activated in host cells. These include the phosphorylation of epidermal growth factor receptor (EGFR) and the consequent activation of the phosphatidylinositol-3 kinase/Akt pathway. While studying this pathway in infected epithelial cells, we observed EGFR depletion at later stages of infection, followed subsequently by a decrease in phospho-EGFR. EGFR loss was not dependent on receptor phosphorylation, or on canonical proteasome- and lysosome-dependent processes. Although a type III secretion mutant (ΔescN) stimulated EGFR phosphorylation, it failed to induce receptor degradation. To identify the specific EPEC effector molecule(s) that influenced EGFR stability, epithelial cells infected with isogenic mutant EPEC strains were examined. An EPEC ΔespF strain failed to induce EGFR degradation, whereas EPEC ΔespZ accentuated receptor loss in infected cells. Given the known and contrasting effects of EspF and EspZ on caspase activation, and the known role of proteases in cleaving EGFR, we explored the effect of caspase inhibitors on infection-dependent EGFR loss. The pan-caspase inhibitor Q-VD-OPh blocked EPEC-induced EGFR cleavage in a dose-dependent manner. Taken together, our data suggest that EPEC EspF stimulates caspase-dependent EGFR cleavage and loss, whereas EspZ inhibits this process. Whereas EGFR phosphorylation contributes to the survival of host cells early in infection, EspF-driven caspase activation and consequent EGFR loss likely induce a precipitous increase in host cell death later in the infectious process.

Original languageEnglish (US)
Pages (from-to)G374-G380
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume307
Issue number3
DOIs
StatePublished - 2014

Keywords

  • Caspase
  • EGFR degradation
  • EGFR phosphorylation
  • EPEC
  • EspF
  • EspZ

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Enteropathogenic Escherichia coli dynamically regulates EGFR signaling in intestinal epithelial cells'. Together they form a unique fingerprint.

  • Cite this