Helicobacter exploits integrin for type IV secretion and kinase activation

Terry Kwok, Dana Zabler, Sylwia Urman, Manfred Rohde, Roland Hartig, Silja Wessler, Rolf Misselwitz, Jürgen Berger, Norbert Sewald, Wolfgang König and Steffen Backert ()
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Terry Kwok: and
Dana Zabler: and
Sylwia Urman: Organic and Bioorganic Chemistry, Bielefeld University, Universitätsstrasse 25
Manfred Rohde: Helmholtz Center for Infection Research, Inhoffen Strasse 7, D-38124 Braunschweig, Germany
Roland Hartig: Otto von Guericke University, Leipziger Strasse 44, D-39120 Magdeburg, Germany
Silja Wessler: Paul Ehrlich Institute, Paul-Ehrlich-Strasse 51-59, D-63225 Langen, Germany
Rolf Misselwitz: Max Delbrück Center for Molecular Medicine, Robert-Roessle-Strasse 10, D-13125 Berlin, Germany
Jürgen Berger: Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076 Tübingen, Germany
Norbert Sewald: Organic and Bioorganic Chemistry, Bielefeld University, Universitätsstrasse 25
Wolfgang König: and
Steffen Backert: and

Nature, 2007, vol. 449, issue 7164, 862-866

Abstract: 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.

Date: 2007
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DOI: 10.1038/nature06187

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