title: Involvement of focal adhesion kinase in invasin-mediated uptake.
abstract: High-efficiency entry of the enteropathogenic bacterium Yersinia pseudotuberculosis into nonphagocytic cells is mediated by the bacterial outer membrane protein invasin. Invasin-mediated uptake requires high affinity binding of invasin to multiple beta1 chain integrin receptors on the host eukaryotic cell. Previous studies using inhibitors have indicated that high-efficiency uptake requires tyrosine kinase activity. In this paper we demonstrate a requirement for focal adhesion kinase (FAK) for invasin-mediated uptake. Overexpression of a dominant interfering form of FAK reduced the amount of bacterial entry. Specifically, the autophosphorylation site of FAK, which is a reported site of c-Src kinase binding, is required for bacterial internalization, as overexpression of a derivative lacking the autophosphorylation site had a dominant interfering effect as well. Cultured cells expressing interfering variants of Src kinase also showed reduced bacterial uptake, demonstrating the involvement of a Src-family kinase in invasin-promoted uptake.
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Alrutz
authors.forename: R R
authors.initials: RR
authors.lastname: Isberg
mesh_terms: D018829:Adhesins, Bacterial; D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D005347:Fibroblasts / Q000201:enzymology / Q000382:microbiology; D051416:Focal Adhesion Protein-Tyrosine Kinases; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D015398:Signal Transduction; D015011:Yersinia pseudotuberculosis / Q000502:physiology*; D015012:Yersinia pseudotuberculosis Infections / Q000382:microbiology*
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D015815:Cell Adhesion Molecules; C053476:invasin, Yersinia; D011505:Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases