c-Abl tyrosine kinase interacts with MAVS and regulates innate immune response.
The tyrosine kinase, c-Abl, plays important roles in many aspects of cellular function. Previous reports showed that c-Abl is involved in NF-kappaB signaling. However, the functions of c-Abl in innate immunity are still unknown. Here we demonstrate that the mitochondrial antiviral signaling (MAVS) protein can be physically associated with c-Abl in vivo and in vitro. MAVS interacted with c-Abl through its Card and TM domain. A phosphotyrosine-specific antibody indicated that MAVS was phosphorylated by c-Abl. Functional impairment of c-Abl attenuated MAVS or VSV induced type-I IFN production. Importantly, c-Abl knockdown in MCF7 cells displayed impaired MAVS-mediated NF-kappaB and IRF3 activation. Taken together, our results suggest that c-Abl modulates innate immune response through MAVS.
Song
Ting
T
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Haidian District, Beijing, China.
Wei
Congwen
C
Zheng
Zirui
Z
Xu
Yang
Y
Cheng
Xiaozhong
X
Yuan
Yuan
Y
Guan
Kai
K
Zhang
Yanhong
Y
Ma
Qingjun
Q
Shi
Wei
W
Zhong
Hui
H
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D007113:Immunity, Innate; D050838:Interferon Regulatory Factor-3 / Q000096:biosynthesis; D016899:Interferon-beta / Q000096:biosynthesis; D016328:NF-kappa B / Q000096:biosynthesis; D010766:Phosphorylation; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; C505371:MAVS protein, human; D016328:NF-kappa B; D016899:Interferon-beta; D016315:Proto-Oncogene Proteins c-abl