title: Focal adhesion kinase is a component of antiviral RIG-I-like receptor signaling.
abstract: Viruses modulate the actin cytoskeleton at almost every step of their cellular journey from entry to egress. Cellular sensing of these cytoskeletal changes may function in the recognition of viral infection. Here we show that focal adhesion kinase (FAK), a focal adhesion localized tyrosine kinase that transmits signals between the extracellular matrix and the cytoplasm, serves as a RIG-I-like receptor antiviral signaling component by directing mitochondrial antiviral signaling adaptor (MAVS) activation. Cells deficient in FAK are highly susceptible to RNA virus infection and attenuated in antiviral signaling. We show that FAK interacts with MAVS at the mitochondrial membrane in a virus infection-dependent manner and potentiates MAVS-mediated signaling via a kinase-independent mechanism. A cysteine protease encoded by enteroviruses cleaves FAK to suppress its role in innate immune signaling. These findings suggest that FAK serves as a link between cytoskeletal perturbations that occur during virus infection and activation of innate immune signaling.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Bozym
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Delorme-Axford
authors.forename: Katharine
authors.initials: K
authors.lastname: Harris
authors.forename: Stefanie
authors.initials: S
authors.lastname: Morosky
authors.forename: Mine
authors.initials: M
authors.lastname: Ikizler
authors.forename: Terence S
authors.initials: TS
authors.lastname: Dermody
authors.forename: Saumendra N
authors.initials: SN
authors.lastname: Sarkar
authors.forename: Carolyn B
authors.initials: CB
authors.lastname: Coyne
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002460:Cell Line; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D006801:Humans; D051336:Mitochondrial Membranes / Q000378:metabolism; D025941:Protein Interaction Mapping; D012328:RNA Viruses / Q000276:immunology*; D015398:Signal Transduction; D010948:Viral Plaque Assay
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C505371:MAVS protein, human; D051416:Focal Adhesion Protein-Tyrosine Kinases