title: Cytosolic Low Molecular Weight FGF2 Orchestrates RIG-I-Mediated Innate Immune Response.
abstract: Fibroblast growth factor (FGF)2,which is one of the 22 members of the FGF family, functions as an extracellular molecule involved in canonical receptor tyrosine kinase signaling. It has been implicated in angiogenesis and the development of the CNS. In this article, we reveal that cytosolic low m.w. isoform (LMW) FGF2 (18 kDa), not its secreted form, plays an unexpected role in the innate immune response. Cytosolic LMW FGF2 directly associated with inactivated RIG-I under physiological conditions, which enhanced RIG-I protein stability, thereby maintaining basal RIG-I levels. However, during RIG-I activation induced by viral RNA, cytosolic FGF2 bound to the caspase recruitment domains of activated RIG-I, which blocked RIG-I-MAVS complex formation. LMW FGF2 deficiency increased type I IFN production, whereas the overexpression of LMW FGF2 exerted the opposite effect. Cytosolic LMW FGF2 functions as a negative regulator in RIG-I-mediated antiviral signaling. This work provides insight into the role of FGF2 in innate immune response.
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China; and.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China; and skyyning@gmail.com ldy612@126.com.
authors.forename: Deyan
authors.initials: D
authors.lastname: Luo
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 skyyning@gmail.com ldy612@126.com.
authors.forename: Ning
authors.initials: N
authors.lastname: Yang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology; D000818:Animals; D003600:Cytosol / Q000276:immunology*; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D016222:Fibroblast Growth Factor 2; D007370:Interferon Type I; D020033:Protein Isoforms; C512612:MAVS protein, mouse; C503356:Ddx58 protein, mouse