幽门螺杆菌的一种粘合素受体

jk1688

Helicobacter exploits integrin for type IV secretion and kinase activation

Terry Kwok1,8, Dana Zabler1, Sylwia Urman3, Manfred Rohde4, Roland Hartig2, Silja Wessler5, Rolf Misselwitz6,8, Jürgen Berger7, Norbert Sewald3, Wolfgang K鰊ig1 & Steffen Backert1

Department of Medical Microbiology, and,
Department of Immunology, Otto von Guericke University, Leipziger Strasse 44, D-39120 Magdeburg, Germany
Department of Chemistry, Organic and Bioorganic Chemistry, Bielefeld University, Universit鋞sstrasse 25, D-33615 Bielefeld, Germany
Helmholtz Center for Infection Research, Department of Microbial Pathogenesis, Inhoffen Strasse 7, D-38124 Braunschweig, Germany
Paul Ehrlich Institute, Paul-Ehrlich-Strasse 51-59, D-63225 Langen, Germany
Max Delbrück Center for Molecular Medicine, Robert-Roessle-Strasse 10, D-13125 Berlin, Germany
Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076 Tübingen, 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.).
Correspondence to: Steffen Backert1 Correspondence and requests for materials should be addressed to S.B. (Email: Steffen.Backert@med.ovgu.de).

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 51 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