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FASEB J. 2016 Dec;30(12):4180-4191. Epub 2016 Sep 8.

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

Author information

1
Institut National de la Recherche Agronomique, Unités Mixtes de Recherche 1282, Infectiologie et Santé Publique, Nouzilly, France; agnes.wiedemann@tours.inra.fr.
2
Université François Rabelais de Tours, Unités Mixtes de Recherche 1282, Infectiologie et Santé Publique, Tours, France.
3
Institut National de la Recherche Agronomique, Unités Mixtes de Recherche 1282, Infectiologie et Santé Publique, Nouzilly, France.
4
Institut National de la Recherche Agronomique, Unités Mixtes de Recherche 85, Unité Physiologie de la Reproduction et des Comportements, Nouzilly, France.
5
Centre National de la Recherche Scientifique, Unités Mixtes de Recherche 7247, Nouzilly, France.
6
L'Institut Français du Cheval et de L'Équitation, Nouzilly, France.
7
Le Studium Loire Valley Institute for Advanced Studies, Orléans, France; and.
8
Institut National de la Recherche Agronomique, Unités Mixtes de Recherche 85, Plate-forme d'Analyse Intégrative des Biomolécules, Nouzilly, France.

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 a host 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.-Wiedemann, A., Mijouin, L., Ayoub, M. A., Barilleau, E., Canepa, S., Teixeira-Gomes, A. P., Le Vern, Y., Rosselin, M., Reiter, E., Velge, P. Identification of the epidermal growth factor receptor as the receptor for Salmonella Rck-dependent invasion.

KEYWORDS:

bacterial internalization; cell signaling; membrane receptor

PMID:
27609774
DOI:
10.1096/fj.201600701R
[Indexed for MEDLINE]

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