Helicobacter exploits integrin for type IV secretion and kinase activation

Kwok T, Zabler D, Urman S, Rohde M, Hartig R, Wessler S, Misselwitz R, Berger J, Sewald N, König W, Backert S (2007)

Publication Type: Journal article

Publication year: 2007

Journal

Nature Nature Research

Book Volume: 449

Pages Range: 862-866

Journal Issue: 7164

DOI: 10.1038/nature06187

Abstract

Integrins are important mammalian receptors involved in normal cellular functions as well as pathogenesis of chronic inflammation and cancer. We propose that integrins are exploited by the gastric pathogen and type-1 carcinogen Helicobacter pylori for injection of the bacterial oncoprotein cytotoxin-associated gene A (CagA) into gastric epithelial cells. Virulent H. pylori express a type-IV secretion pilus that injects CagA into the host cell; CagA then becomes tyrosine-phosphorylated by Src family kinases. However, the identity of the host cell receptor involved in this process has remained unknown. Here we show that the H. pylori CagL protein is a specialized adhesin that is targeted to the pilus surface, where it binds to and activates integrin α5β1 receptor on gastric epithelial cells through an arginine-glycine-aspartate motif. This interaction triggers CagA delivery into target cells as well as activation of focal adhesion kinase and Src. Our findings provide insights into the role of integrins in H.-pylori-induced pathogenesis. CagL may be exploited as a new molecular tool for our further understanding of integrin signalling. ©2007 Nature Publishing Group.

Authors with CRIS profile

Steffen Backert

Involved external institutions

Paul Ehrlich Institute / Paul-Ehrlich-Institut – Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel (PEI) DE Germany (DE) Otto-von-Guericke-Universität Magdeburg DE Germany (DE) Universität Bielefeld DE Germany (DE) Helmholtz-Zentrum für Infektionsforschung (HZI) DE Germany (DE) Max-Planck-Institut für Entwicklungsbiologie / Max Planck Institute for Developmental Biology DE Germany (DE) Freie Universität Berlin DE Germany (DE)

How to cite

APA:

Kwok, T., Zabler, D., Urman, S., Rohde, M., Hartig, R., Wessler, S.,... Backert, S. (2007). Helicobacter exploits integrin for type IV secretion and kinase activation. Nature, 449(7164), 862-866. https://doi.org/10.1038/nature06187

MLA:

Kwok, Terry, et al. "Helicobacter exploits integrin for type IV secretion and kinase activation." Nature 449.7164 (2007): 862-866.

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