Document Detail


Focal adhesion kinase is a component of antiviral RIG-I-like receptor signaling.
MedLine Citation:
PMID:  22341464     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Rebecca A Bozym; Elizabeth Delorme-Axford; Katharine Harris; Stefanie Morosky; Mine Ikizler; Terence S Dermody; Saumendra N Sarkar; Carolyn B Coyne
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell host & microbe     Volume:  11     ISSN:  1934-6069     ISO Abbreviation:  Cell Host Microbe     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-20     Completed Date:  2012-06-06     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  101302316     Medline TA:  Cell Host Microbe     Country:  United States    
Other Details:
Languages:  eng     Pagination:  153-66     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing / metabolism*
Cell Line
Focal Adhesion Protein-Tyrosine Kinases / metabolism*
Humans
Mitochondrial Membranes / metabolism
Protein Interaction Mapping
RNA Viruses / immunology*
Signal Transduction*
Viral Plaque Assay
Grant Support
ID/Acronym/Agency:
CA68485/CA/NCI NIH HHS; DK20593/DK/NIDDK NIH HHS; R01 AI081759/AI/NIAID NIH HHS; R01 AI081759/AI/NIAID NIH HHS; R01 AI081759-04/AI/NIAID NIH HHS; R37 AI038296/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/VISA protein, human; EC 2.7.10.2/Focal Adhesion Protein-Tyrosine Kinases
Comments/Corrections

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