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Virulent <jats:italic>H. pylori<\/jats:italic> strains harbor a type IV secretion system (T4SS) encoded by the <jats:italic>cag<\/jats:italic> pathogenicity island. This T4SS injects the CagA protein into gastric epithelial cells leading to actin\u2010cytoskeletal rearrangements followed by cell elongation and scattering. Here we report that PMA (4\u03b2\u2010phorbol\u201012\u2010myristate\u201013\u2010acetate), a well\u2010known cell\u2010permeable activator of protein kinase C (PKC), induces a remarkably similar cellular phenotype as compared to infection with <jats:italic>H. pylori<\/jats:italic>. 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\u2010specific silencing RNAs and pharmacological inhibitors we found that two isoforms, PKC\u2010\u03b1 and PKC\u2010\u03b4, were essential for both PMA\u2010 and <jats:italic>H. pylori<\/jats:italic>\u2010induced elongation phenotype. Furthermore, we provide evidence that PKC\u2010\u03b4 activity is profoundly stimulated during the course of infection using activation\u2010specific antibodies against PKC phosphorylated at threonine residue 505 or serine residue 660. Infection with <jats:italic>H. pylori<\/jats:italic> wild\u2010type and mutants showed that at least two bacterial factors activate PKC\u2010\u03b4 in a time\u2010dependent manner, one of which is CagA. Immunofluorescence microscopy studies further demonstrated that phosphorylated PKC\u2010\u03b4 is accumulated and recruited to dynamic actin\u2010structures at the cell membrane. Finally, we show that PKC\u2010\u03b4 specifically targets Raf kinase to stimulate the Erk1\/2 kinase pathway, which is also crucial for phenotypical outcome. Thus, PKC\u2010\u03b4 is another important mediator of <jats:italic>H. pylori<\/jats:italic>\u2010induced pathogenesis. Cell Motil. Cytoskeleton 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/cm.20373","type":"journal-article","created":{"date-parts":[[2009,5,12]],"date-time":"2009-05-12T20:55:59Z","timestamp":1242161759000},"page":"874-892","source":"Crossref","is-referenced-by-count":20,"title":["<i>Helicobacter pylori<\/i> activates protein kinase C delta to control Raf in MAP kinase signalling: Role in AGS epithelial cell scattering and 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