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

Item Type:	Article
Title:	The Helicobacter pylori CagA protein induces cortactin dephosphorylation and actin rearrangement by c-Src inactivation
Creators Name:	Selbach, M. and Moese, S. and Hurwitz, R. and Hauck, C.R. and Meyer, T.F. and Backert, S.
Abstract:	The gastric pathogen Helicobacter pylori translocates the CagA protein into epithelial cells by a type IV secretion process. Translocated CagA is tyrosine phosphorylated (CagA(P-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 CagA(P-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, CagA(P-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.
Keywords:	Actin Cytoskeleton, Molecular Pathogenesis, Type IV Secretion, Tyrosine Phosphorylation
Source:	EMBO Journal
ISSN:	0261-4189
Publisher:	Nature Publishing Group
Volume:	22
Number:	3
Page Range:	515-528
Date:	3 February 2003
Official Publication:	https://doi.org/10.1093/emboj/cdg050
PubMed:	View item in PubMed

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