Helicobacter exploits integrin for type IV secretion and kinase activation

Terry Kwok, Dana Zabler, Sylwia Urman, Manfred Rohde, Roland Hartig, Silja Wessler, Rolf Misselwitz, Jurgen Berger, Norbert Sewald, Wolfgang Konig, Steffen Backert

Research output: Contribution to journalArticleResearchpeer-review

444 Citations (Scopus)

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 alpha5beta1 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.
Original languageEnglish
Pages (from-to)862 - 866
Number of pages5
JournalNature
Volume449
Issue number7164
Publication statusPublished - 2007
Externally publishedYes

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