Identification of the epidermal growth factor receptor as the receptor for Salmonella Rck-dependent invasion

Agnès Wiedemann, Lily Mijouin, Mohammed Akli Ayoub, Emilie Barilleau, Sylvie Canepa, Ana Paula Teixeira-Gomes, Yves Le Vern, Manon Rosselin, Eric Reiter, Philippe Velge

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

The Salmonella Rck outer membrane protein binds to the cell surface, which leads to bacterial internalization via a Zipper mechanism. This invasion process requires induction of cellular signals, including phosphorylation of tyrosine proteins, and activation of c-Src and PI3K, which arises as a result of an interaction with ahost cell surface receptor. In this study, epidermal growth factor receptor (EGFR) was identified as the cell signaling receptor required for Rck-mediated adhesion and internalization. First, Rck-mediated adhesion and internalization were shown to be altered when EGFR expression and activity were modulated. Then, immunoprecipitations were performed to demonstrate the Rck-EGFR interaction. Furthermore, surface plasmon resonance biosensor and homogeneous time-resolved fluorescence technologies were used to demonstrate the direct interaction of Rck with the extracellular domain of human EGFR. Finally, our study strongly suggests a noncompetitive binding of Rck and EGF to EGFR. Overall, these results demonstrate that Rck is able to bind to EGFR and thereby establish a tight adherence to provide a signaling cascade, which leads to internalization of Rck-expressing bacteria.

Original languageEnglish
Pages (from-to)4180-4191
Number of pages12
JournalFASEB Journal
Volume30
Issue number12
DOIs
Publication statusPublished - Dec 2016
Externally publishedYes

Keywords

  • Bacterial internalization
  • Cell signaling
  • Membrane receptor

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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