title: Serine phosphorylation of cortactin controls focal adhesion kinase activity and cell scattering induced by Helicobacter pylori.
abstract: Cell migration and invasion require the coordinated regulation of cytoskeletal architectural changes by signaling factors, including the actin-binding protein cortactin. Bacterial and viral pathogens subvert these signaling factors to promote their uptake, spread and dissemination. We show that the gastric pathogen Helicobacter pylori (Hp) targets cortactin by two independent processes leading to its tyrosine dephosphorylation and serine phosphorylation to regulate cell scattering and elongation. The phosphorylation status of cortactin dictates its subcellular localization and signaling partners. Upon infection, cortactin was found to interact with and stimulate the kinase activity of focal adhesion kinase (FAK). This interaction required the SH3 domain and phosphorylation of cortactin at serine 405 and a proline-rich sequence in FAK. Using Hp as a model, this study unravels a previously unrecognized FAK activation pathway. We propose that Hp targets cortactin to protect the gastric epithelium from excessive cell lifting and ensure sustained infection in the stomach.
authors.affiliation: Department of Microbiology, Otto von Guericke University, Leipziger Strasse 44, D-39120 Magdeburg, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Tegtmeyer
authors.forename: Ruth
authors.initials: R
authors.lastname: Wittelsberger
authors.forename: Roland
authors.initials: R
authors.lastname: Hartig
authors.forename: Silja
authors.initials: S
authors.lastname: Wessler
authors.forename: Narcisa
authors.initials: N
authors.lastname: Martinez-Quiles
authors.forename: Steffen
authors.initials: S
authors.lastname: Backert
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D051356:Cortactin / Q000235:genetics / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016481:Helicobacter Infections / Q000201:enzymology / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D016480:Helicobacter pylori / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D012694:Serine / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D051356:Cortactin; D012694:Serine; D051417:Focal Adhesion Kinase 1