title: CagA of Helicobacter pylori interacts with and inhibits the serine-threonine kinase PRK2.
abstract: CagA is a multifunctional toxin of Helicobacter pylori that is secreted into host epithelial cells by a type IV secretion system. Following host cell translocation, CagA interferes with various host-cell signalling pathways. Most notably this toxin is involved in the disruption of apical-basolateral cell polarity and cell adhesion, as well as in the induction of cell proliferation, migration and cell morphological changes. These are processes that also play an important role in epithelial-to-mesenchymal transition and cancer cell invasion. In fact, CagA is considered as the only known bacterial oncoprotein. The cellular effects are triggered by a variety of CagA activities including the inhibition of serine-threonine kinase Par1b/MARK2 and the activation of tyrosine phosphatase SHP-2. Additionally, CagA was described to affect the activity of Src family kinases and C-terminal Src kinase (Csk) suggesting that interference with multiple cellular kinase- and phosphatase-associated signalling pathways is a major function of CagA. Here, we describe the effect of CagA on protein kinase C-related kinase 2 (PRK2), which acts downstream of Rho GTPases and is known to affect cytoskeletal rearrangements and cell polarity. CagA interacts with PRK2 and inhibits its kinase activity. Because PRK2 has been linked to cytoskeletal rearrangements and establishment of cell polarity, we suggest that CagA may hijack PRK2 to further manipulate cancer-related signalling pathways.
authors.affiliation: Department of Health Sciences, School of Arts and Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
authors.forename: Jyoti Prasad
authors.initials: JP
authors.lastname: Mishra
authors.affiliation: Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: David
authors.initials: D
authors.lastname: Cohen
authors.affiliation: Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Zamperone
authors.affiliation: Laboratory of Structural Microbiology, The Rockefeller University, New York, NY, USA.
authors.forename: Dragana
authors.initials: D
authors.lastname: Nesic
authors.affiliation: Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Muesch
authors.affiliation: Department of Health Sciences, School of Arts and Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
authors.forename: Markus
authors.initials: M
authors.lastname: Stein
mesh_terms: D000942:Antigens, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D016764:Cell Polarity; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000382:microbiology / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition; D016480:Helicobacter pylori / Q000502:physiology*; D054884:Host-Pathogen Interactions; D011485:Protein Binding; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori; C061570:protein kinase N; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C