Helicobacter pylori activates protein kinase C delta to control Raf in MAP kinase signalling: Role in AGS epithelial cell scattering and elongation
Brandt S, Wessler S, Hartig R, Backert S (2009)
Publication Type: Journal article
Publication year: 2009
Journal
Book Volume: 66
Pages Range: 874-892
Journal Issue: 10
DOI: 10.1002/cm.20373
Abstract
Helicobacter pylori is a major etiological agent in the development of chronic gastritis, duodenal ulcer and gastric carcinoma in humans. Virulent H. pylori strains harbor a type IV secretion system (T4SS) encoded by the cag pathogenicity island. This T4SS injects the CagA protein into gastric epithelial cells leading to actin-cytoskeletal rearrangements followed by cell elongation and scattering. Here we report that PMA (4β-phorbol-12-myristate-13- acetate), a well-known cell-permeable activator of protein kinase C (PKC), induces a remarkably similar cellular phenotype as compared to infection with H. pylori. PKCs comprise a large family of serine/threonine kinases which are important for multiple physiological processes of host cells. We therefore investigated the role of individual PKC members and the signalling pathways involved in phenotypical outcome. Using isoform-specific silencing RNAs and pharmacological inhibitors we found that two isoforms, PKC-α and PKC-δ, were essential for both PMA- and H. pylori-induced elongation phenotype. Furthermore, we provide evidence that PKC-δ activity is profoundly stimulated during the course of infection using activation-specific antibodies against PKC phosphorylated at threonine residue 505 or serine residue 660. Infection with H. pylori wild-type and mutants showed that at least two bacterial factors activate PKC-δ in a time-dependent manner, one of which is CagA. Immunofluorescence microscopy studies further demonstrated that phosphorylated PKC-δ is accumulated and recruited to dynamic actin-structures at the cell membrane. Finally, we show that PKC-δ specifically targets Raf kinase to stimulate the Erk1/2 kinase pathway, which is also crucial for phenotypical outcome. Thus, PKC-δ is another important mediator of H. pylori-induced pathogenesis. © 2009 Wiley-Liss, Inc.
Authors with CRIS profile
Involved external institutions
Otto-von-Guericke-Universität Magdeburg
Germany (DE)
Paul Ehrlich Institute / Paul-Ehrlich-Institut – Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel (PEI)
Germany (DE)
University College Dublin (UCD)
Ireland (IE)
Germany (DE)
Paul Ehrlich Institute / Paul-Ehrlich-Institut – Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel (PEI)
Germany (DE)
University College Dublin (UCD)
Ireland (IE)
How to cite
APA:
Brandt, S., Wessler, S., Hartig, R., & Backert, S. (2009). Helicobacter pylori activates protein kinase C delta to control Raf in MAP kinase signalling: Role in AGS epithelial cell scattering and elongation. Cell Motility and the Cytoskeleton, 66(10), 874-892. https://doi.org/10.1002/cm.20373
MLA:
Brandt, Sabine, et al. "Helicobacter pylori activates protein kinase C delta to control Raf in MAP kinase signalling: Role in AGS epithelial cell scattering and elongation." Cell Motility and the Cytoskeleton 66.10 (2009): 874-892.
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