粘合素（Integrins）是一个重要的细胞粘附受体家族，参与各种不同的信号作用过程，是若干种细菌和病毒病原体粘附或入侵的目标。现在，一种粘合素已被识别出是肠道病原体幽门螺杆菌的受体。该病原体的CagL pilus蛋白可结合到宿主细胞表面受体粘合素α5β1上，这会触发致癌蛋白CagA（细胞毒素相关的基因A）被注射进宿主细胞中。这项工作表明，CagL是治疗由一些幽门螺杆菌菌种引起的肠道疾病的一个可能的药物作用目标。
原始出处:
Nature 449, 862-866 (18 October 2007) | doi:10.1038/nature06187; Received 24 May 2007; Accepted 21 August 2007
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 König1 & 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, Universitätsstrasse 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.
