粘合素（Integrins）是一個(gè)重要的細(xì)胞粘附受體家族,，參與各種不同的信號(hào)作用過(guò)程,，是若干種細(xì)菌和病毒病原體粘附或入侵的目標(biāo)?，F(xiàn)在,，一種粘合素已被識(shí)別出是腸道病原體幽門螺桿菌的受體,。該病原體的CagL pilus蛋白可結(jié)合到宿主細(xì)胞表面受體粘合素α5β1上，這會(huì)觸發(fā)致癌蛋白CagA（細(xì)胞毒素相關(guān)的基因A）被注射進(jìn)宿主細(xì)胞中,。這項(xiàng)工作表明，CagL是治療由一些幽門螺桿菌菌種引起的腸道疾病的一個(gè)可能的藥物作用目標(biāo),。
原始出處:
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: [email protected]).
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.
