| Focal adhesion kinase is a component of antiviral RIG-I-like receptor signaling. | |
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MedLine Citation:
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PMID: 22341464 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cell host & microbe Volume: 11 ISSN: 1934-6069 ISO Abbreviation: Cell Host Microbe Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-02-20 Completed Date: 2012-06-06 Revised Date: 2012-06-11 |
Medline Journal Info:
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Nlm Unique ID: 101302316 Medline TA: Cell Host Microbe Country: United States |
Other Details:
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Languages: eng Pagination: 153-66 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adaptor Proteins, Signal Transducing
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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:
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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:
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0/Adaptor Proteins, Signal Transducing; 0/VISA protein, human; EC 2.7.10.2/Focal Adhesion Protein-Tyrosine Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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