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The Helicobacter pylori CagA protein induces cortactin dephosphorylation and actin rearrangement by c-Src inactivation

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Datum

2002

Autor:innen

Selbach, Matthias
Moese, Stefan
Hurwitz, Robert
Meyer, Thomas F.
Backert, Steffen

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The EMBO Journal. 2002, 22(3), pp. 515-528. ISSN 0261-4189. eISSN 1460-2075. Available under: doi: 10.1093/emboj/cdg050

Zusammenfassung

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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Fachgebiet (DDC)
570 Biowissenschaften, Biologie

Schlagwörter

actin cytoskeleton, molecular pathogenesis, type IV secretion, tyrosine phosphorylation

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ISO 690SELBACH, Matthias, Stefan MOESE, Robert HURWITZ, Christof R. HAUCK, Thomas F. MEYER, Steffen BACKERT, 2002. The Helicobacter pylori CagA protein induces cortactin dephosphorylation and actin rearrangement by c-Src inactivation. In: The EMBO Journal. 2002, 22(3), pp. 515-528. ISSN 0261-4189. eISSN 1460-2075. Available under: doi: 10.1093/emboj/cdg050
BibTex
@article{Selbach2002Helic-8609,
  year={2002},
  doi={10.1093/emboj/cdg050},
  title={The Helicobacter pylori CagA protein induces cortactin dephosphorylation and actin rearrangement by c-Src inactivation},
  number={3},
  volume={22},
  issn={0261-4189},
  journal={The EMBO Journal},
  pages={515--528},
  author={Selbach, Matthias and Moese, Stefan and Hurwitz, Robert and Hauck, Christof R. and Meyer, Thomas F. and Backert, Steffen}
}
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