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Helicobacter exploits integrin for type IV secretion and kinase activation

Item Type:Article
Title:Helicobacter exploits integrin for type IV secretion and kinase activation
Creators Name:Kwok, T. and Zabler, D. and Urman, S. and Rohde, M. and Hartig, R. and Wessler, S. and Misselwitz, R. and Berger, J.M. and Sewald, N. and Koenig, W. and Backert, S.
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 {alpha}5{beta}1 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.
Keywords:Bacterial Antigens, Bacterial Fimbriae, Bacterial Proteins, Cell Line, Enzyme Activation, Epithelial Cells, Focal Adhesion Protein-Tyrosine Kinases, Helicobacter pylori, Integrin {alpha}5{beta}1, Oligopeptides, Phosphorylation, Protein Binding, Protein Interaction Domains and Motifs, Proto-Oncogene Proteins pp60(c-src)
Publisher:Nature Publishing Group (U.K.)
Page Range:862-866
Date:18 October 2007
Official Publication:https://doi.org/10.1038/nature06187
PubMed:View item in PubMed

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