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Helicobacter exploits integrin for type IV secretion and kinase activation

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  • Terry Kwok

    (and
    Present addresses: University of Zürich, Institute of Medical Virology, Gloriastrasse 30/32, CH-8006 Zürich, Switzerland (T.K.); Institute for Immuno Genetics, Charité University Clinics Berlin, Humboldt University Berlin, Spandauer Damm 130, D-14050 Berlin, Germany (R.M.).)

  • 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
    Present addresses: University of Zürich, Institute of Medical Virology, Gloriastrasse 30/32, CH-8006 Zürich, Switzerland (T.K.); Institute for Immuno Genetics, Charité University Clinics Berlin, Humboldt University Berlin, Spandauer Damm 130, D-14050 Berlin, Germany (R.M.).)

  • 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)

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.

Suggested Citation

  • Terry Kwok & Dana Zabler & Sylwia Urman & Manfred Rohde & Roland Hartig & Silja Wessler & Rolf Misselwitz & Jürgen Berger & Norbert Sewald & Wolfgang König & Steffen Backert, 2007. "Helicobacter exploits integrin for type IV secretion and kinase activation," Nature, Nature, vol. 449(7164), pages 862-866, October.
    • Handle: RePEc:nat:nature:v:449:y:2007:i:7164:d:10.1038_nature06187
    DOI: 10.1038/nature06187
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    Cited by:

    1. Carmen Aguilar & Mindaugas Pauzuolis & Malvika Pompaiah & Ehsan Vafadarnejad & Panagiota Arampatzi & Mara Fischer & Dominik Narres & Mastura Neyazi & Özge Kayisoglu & Thomas Sell & Nils Blüthgen & Mar, 2022. "Helicobacter pylori shows tropism to gastric differentiated pit cells dependent on urea chemotaxis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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