Invasion of Host Cells bySalmonella typhimuriumRequires Focal Adhesion Kinase and p130Cas
- 1 November 2006
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 17 (11), 4698-4708
- https://doi.org/10.1091/mbc.e06-06-0492
Abstract
Salmonella typhimurium colonizes the intestinal epithelium by injecting an array of effector proteins into host cells that induces phagocytic uptake of attached bacteria. However, the host molecules targeted by these effectors remain poorly defined. Here, we demonstrate that S. typhimurium induces formation of focal adhesion-like complexes at sites of bacterial attachment and that both focal adhesion kinase (FAK) and the scaffolding protein p130Cas are required for Salmonella uptake. Entry of Salmonella into FAK−/− cells is dramatically impaired and can be restored to control levels by expression of wild-type FAK. Surprisingly, reconstitution of bacterial internalization requires neither the kinase domain of FAK nor activation of c-Src, but does require a C-terminal PXXP motif through which FAK interacts with Cas. Infection of Cas−/− cells is also impaired, and reconstitution of invasiveness requires the central Cas YXXP repeat domain. The invasion defect in Cas−/− cells can be suppressed by overexpression of FAK, suggesting a functional link between FAK and Cas in the regulation of Salmonella invasion. Together, these findings reveal a novel role for focal adhesion proteins in the invasion of host cells by Salmonella.This publication has 51 references indexed in Scilit:
- p130 but Not Paxillin Is Essential for Caco-2 Intestinal Epithelial Cell Spreading and Migration on Collagen IVPublished by Elsevier BV ,2005
- Focal adhesion kinase: in command and control of cell motilityNature Reviews Molecular Cell Biology, 2005
- Differential Regulation of Cell Migration, Actin Stress Fiber Organization, and Cell Transformation by Functional Domains of Crk-associated SubstratePublished by Elsevier BV ,2002
- The Association of ASAP1, an ADP Ribosylation Factor-GTPase Activating Protein, with Focal Adhesion Kinase Contributes to the Process of Focal Adhesion AssemblyMolecular Biology of the Cell, 2002
- Mechanisms of CAS Substrate Domain Tyrosine Phosphorylation by FAK and SrcMolecular and Cellular Biology, 2001
- Binding of the Shigella protein IpaA to vinculin induces F-actin depolymerizationThe EMBO Journal, 1999
- Characterization of Graf, the GTPase-activating Protein for Rho Associated with Focal Adhesion KinasePublished by Elsevier BV ,1998
- Modulation of bacterial entry into epithelial cells by association between vinculin and the Shigella IpaA invasinThe EMBO Journal, 1997
- The Related Adhesion Focal Tyrosine Kinase Is Tyrosine-phosphorylated after β1-Integrin Stimulation in B Cells and Binds to p130casPublished by Elsevier BV ,1997
- Requirement of CDC42 for Salmonella -Induced Cytoskeletal and Nuclear ResponsesScience, 1996