Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Cell Host Microbe. 2012 Feb 16;11(2):153-66. doi: 10.1016/j.chom.2012.01.008.
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.
病毒在其从进入到离开细胞的整个生命周期的几乎每一步都对肌动蛋白细胞骨架进行调节。细胞对这些细胞骨架变化的感知可能在识别病毒感染中发挥作用。在这里，我们表明，粘着斑激酶（FAK）作为一种局灶黏着斑定位的酪氨酸激酶，在细胞外基质和细胞质之间传递信号，通过指导线粒体抗病毒信号接头（MAVS）的激活，充当 RIG-I 样受体抗病毒信号成分。FAK 缺陷的细胞极易受到 RNA 病毒感染，并在抗病毒信号中受到抑制。我们表明，FAK 在病毒感染依赖性的方式下与线粒体膜上的 MAVS 相互作用，并通过非激酶依赖机制增强 MAVS 介导的信号转导。肠道病毒编码的一种半胱氨酸蛋白酶切割 FAK，抑制其在先天免疫信号中的作用。这些发现表明，FAK 作为病毒感染期间发生的细胞骨架扰动与先天免疫信号激活之间的联系。
