Cargando…

Cortactin Is Required for Efficient FAK, Src and Abl Tyrosine Kinase Activation and Phosphorylation of Helicobacter pylori CagA

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 h...

Descripción completa

Detalles Bibliográficos
Autores principales: Knorr, Jakob, Sharafutdinov, Irshad, Fiedler, Florian, Soltan Esmaeili, Delara, Rohde, Manfred, Rottner, Klemens, Backert, Steffen, Tegtmeyer, Nicole
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199859/
https://www.ncbi.nlm.nih.gov/pubmed/34205064
http://dx.doi.org/10.3390/ijms22116045
_version_ 1783707474237325312
author Knorr, Jakob
Sharafutdinov, Irshad
Fiedler, Florian
Soltan Esmaeili, Delara
Rohde, Manfred
Rottner, Klemens
Backert, Steffen
Tegtmeyer, Nicole
author_facet Knorr, Jakob
Sharafutdinov, Irshad
Fiedler, Florian
Soltan Esmaeili, Delara
Rohde, Manfred
Rottner, Klemens
Backert, Steffen
Tegtmeyer, Nicole
author_sort Knorr, Jakob
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8199859
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-81998592021-06-14 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 Int J Mol Sci Article 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. MDPI 2021-06-03 /pmc/articles/PMC8199859/ /pubmed/34205064 http://dx.doi.org/10.3390/ijms22116045 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Knorr, Jakob
Sharafutdinov, Irshad
Fiedler, Florian
Soltan Esmaeili, Delara
Rohde, Manfred
Rottner, Klemens
Backert, Steffen
Tegtmeyer, Nicole
Cortactin Is Required for Efficient FAK, Src and Abl Tyrosine Kinase Activation and Phosphorylation of Helicobacter pylori CagA
title Cortactin Is Required for Efficient FAK, Src and Abl Tyrosine Kinase Activation and Phosphorylation of Helicobacter pylori CagA
title_full Cortactin Is Required for Efficient FAK, Src and Abl Tyrosine Kinase Activation and Phosphorylation of Helicobacter pylori CagA
title_fullStr Cortactin Is Required for Efficient FAK, Src and Abl Tyrosine Kinase Activation and Phosphorylation of Helicobacter pylori CagA
title_full_unstemmed Cortactin Is Required for Efficient FAK, Src and Abl Tyrosine Kinase Activation and Phosphorylation of Helicobacter pylori CagA
title_short Cortactin Is Required for Efficient FAK, Src and Abl Tyrosine Kinase Activation and Phosphorylation of Helicobacter pylori CagA
title_sort cortactin is required for efficient fak, src and abl tyrosine kinase activation and phosphorylation of helicobacter pylori caga
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199859/
https://www.ncbi.nlm.nih.gov/pubmed/34205064
http://dx.doi.org/10.3390/ijms22116045
work_keys_str_mv AT knorrjakob cortactinisrequiredforefficientfaksrcandabltyrosinekinaseactivationandphosphorylationofhelicobacterpyloricaga
AT sharafutdinovirshad cortactinisrequiredforefficientfaksrcandabltyrosinekinaseactivationandphosphorylationofhelicobacterpyloricaga
AT fiedlerflorian cortactinisrequiredforefficientfaksrcandabltyrosinekinaseactivationandphosphorylationofhelicobacterpyloricaga
AT soltanesmaeilidelara cortactinisrequiredforefficientfaksrcandabltyrosinekinaseactivationandphosphorylationofhelicobacterpyloricaga
AT rohdemanfred cortactinisrequiredforefficientfaksrcandabltyrosinekinaseactivationandphosphorylationofhelicobacterpyloricaga
AT rottnerklemens cortactinisrequiredforefficientfaksrcandabltyrosinekinaseactivationandphosphorylationofhelicobacterpyloricaga
AT backertsteffen cortactinisrequiredforefficientfaksrcandabltyrosinekinaseactivationandphosphorylationofhelicobacterpyloricaga
AT tegtmeyernicole cortactinisrequiredforefficientfaksrcandabltyrosinekinaseactivationandphosphorylationofhelicobacterpyloricaga