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| Subject Categories: Signal Transduction | Microbiology & Pathogens |
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| The EMBO Journal
(2003) 22, 515–528, doi:10.1093/emboj/cdg050 |
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| The Helicobacter pylori CagA protein induces cortactin dephosphorylation and actin rearrangement by c-Src inactivation |
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| Matthias Selbach1, Stefan Moese1, Robert Hurwitz1, Christof R. Hauck2, Thomas F. Meyer1 and Steffen Backert1 |
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1 Max-Planck-Institut für Infektionsbiologie, Abt. Molekulare Biologie, Schumannstrasse 20/21, D-10117 Berlin, Germany 2 Zentrum für Infektionsforschung, Universität Würzburg, Röntgenring 11, D-97070 Würzburg, Germany To whom correspondence should be addressed Thomas F. Meyer, meyer@mpiib-berlin.mpg.de Received 31 July 2002; Revised 8 November 2002; Accepted 3 December 2002. |
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| Abstract |
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| The gastric pathogen Helicobacter pylori translocates the CagA protein into epithelial cells by a type IV secretion process. Translocated CagA is tyrosine phosphorylated (CagAP-Tyr) on specific EPIYA sequence repeats by Src family tyrosine kinases. Phos phorylation of CagA induces the dephosphorylation of as yet unidentified cellular proteins, rearrangements of the host cell actin cytoskeleton and cell scattering. We show here that CagAP-Tyr inhibits the catalytic activity of c-Src in vivo and in vitro. c-Src inactivation leads to tyrosine dephosphorylation of the actin binding protein cortactin. Concomitantly, cortactin is specifically redistributed to actin-rich cellular protrusions. c-Src inactivation and cortactin dephosphorylation are required for rearrangements of the actin cytoskeleton. Moreover, CagAP-Tyr-mediated c-Src inhibition downregulates further CagA phosphorylation through a negative feedback loop. This is the first report of a bacterial virulence factor that inhibits signalling of a eukaryotic tyrosine kinase and on a role of c-Src inactivation in host cell cytoskeletal rearrangements. |
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| Keywords: actin cytoskeleton, molecular pathogenesis, type IV secretion, tyrosine phosphorylation |
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