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Cortactin Is Required for Efficient FAK, Src and Abl Tyrosine Kinase Activation and Phosphorylation of Helicobacter pylori CagA.
Knorr, Jakob; Sharafutdinov, Irshad; Fiedler, Florian; Soltan Esmaeili, Delara; Rohde, Manfred; Rottner, Klemens; Backert, Steffen; Tegtmeyer, Nicole.
Afiliación
  • Knorr J; Department of Biology, Division of Microbiology, Friedrich-Alexander University of Erlangen-Nuremberg, 91058 Erlangen, Germany.
  • Sharafutdinov I; Department of Biology, Division of Microbiology, Friedrich-Alexander University of Erlangen-Nuremberg, 91058 Erlangen, Germany.
  • Fiedler F; Department of Biology, Division of Microbiology, Friedrich-Alexander University of Erlangen-Nuremberg, 91058 Erlangen, Germany.
  • Soltan Esmaeili D; Department of Biology, Division of Microbiology, Friedrich-Alexander University of Erlangen-Nuremberg, 91058 Erlangen, Germany.
  • Rohde M; Central Facility for Microscopy, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
  • Rottner K; Department of Cell Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
  • Backert S; Division of Molecular Cell Biology, Zoological Institute, Technische Universität Braunschweig, 38106 Braunschweig, Germany.
  • Tegtmeyer N; Department of Biology, Division of Microbiology, Friedrich-Alexander University of Erlangen-Nuremberg, 91058 Erlangen, Germany.
Int J Mol Sci ; 22(11)2021 Jun 03.
Article en En | MEDLINE | ID: mdl-34205064
Cortactin is a well-known regulatory protein of the host actin cytoskeleton and represents an attractive target of microbial pathogens like Helicobacter pylori. H. pylori manipulates cortactin's phosphorylation status by type-IV secretion-dependent injection of its virulence protein CagA. Multiple host tyrosine kinases, like FAK, Src, and Abl, are activated during infection, but the pathway(s) involved is (are) not yet fully established. Among them, Src and Abl target CagA and stimulate tyrosine phosphorylation of the latter at its EPIYA-motifs. To investigate the role of cortactin in more detail, we generated a CRISPR/Cas9 knockout of cortactin in AGS gastric epithelial cells. Surprisingly, we found that FAK, Src, and Abl kinase activities were dramatically downregulated associated with widely diminished CagA phosphorylation in cortactin knockout cells compared to the parental control. Together, we report here a yet unrecognized cortactin-dependent signaling pathway involving FAK, Src, and Abl activation, and controlling efficient phosphorylation of injected CagA during infection. Thus, the cortactin status could serve as a potential new biomarker of gastric cancer development.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Proteínas Bacterianas / Proteínas Oncogénicas v-abl / Helicobacter pylori / Infecciones por Helicobacter / Quinasa 1 de Adhesión Focal / Antígenos Bacterianos Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2021 Tipo del documento: Article País de afiliación: Alemania

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Proteínas Bacterianas / Proteínas Oncogénicas v-abl / Helicobacter pylori / Infecciones por Helicobacter / Quinasa 1 de Adhesión Focal / Antígenos Bacterianos Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2021 Tipo del documento: Article País de afiliación: Alemania