c-Abl tyrosine kinase interacts with MAVS and regulates innate immune response

Song, Ting; Wei, Congwen; Zheng, Zirui; Xu, Yang; Cheng, Xiaozhong; Yuan, Yuan; Guan, Kai; Zhang, Yanhong; Ma, Qingjun; Shi, Wei; Zhong, Hui

doi:10.1016/j.febslet.2009.11.025

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Volume 584, Issue 1 , Pages 33-38, 4 January 2010

c-Abl tyrosine kinase interacts with MAVS and regulates innate immune response

Edited by Giulio Superti-Furga

Ting Song
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Room 841, East District Building, No. 27 Taiping Road, Haidian District, Beijing 100850, China
- These authors contributed equally to this work.
Congwen Wei
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Room 841, East District Building, No. 27 Taiping Road, Haidian District, Beijing 100850, China
- These authors contributed equally to this work.
Zirui Zheng
- Key Laboratory for Molecular Enzymology and Engineering, Ji Lin University, Changchun 130021, China
- These authors contributed equally to this work.
Yang Xu
- Key Laboratory for Molecular Enzymology and Engineering, Ji Lin University, Changchun 130021, China
Xiaozhong Cheng
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Room 841, East District Building, No. 27 Taiping Road, Haidian District, Beijing 100850, China
Yuan Yuan
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Room 841, East District Building, No. 27 Taiping Road, Haidian District, Beijing 100850, China
Kai Guan
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Room 841, East District Building, No. 27 Taiping Road, Haidian District, Beijing 100850, China
Yanhong Zhang
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Room 841, East District Building, No. 27 Taiping Road, Haidian District, Beijing 100850, China
Qingjun Ma
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Room 841, East District Building, No. 27 Taiping Road, Haidian District, Beijing 100850, China
Wei Shi
- Key Laboratory for Molecular Enzymology and Engineering, Ji Lin University, Changchun 130021, China
- Corresponding authors. Fax: +86 10 66931809.
Hui Zhong
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Room 841, East District Building, No. 27 Taiping Road, Haidian District, Beijing 100850, China
- Corresponding authors. Fax: +86 10 66931809.

Received 29 September 2009; received in revised form 6 November 2009; accepted 8 November 2009. published online 13 November 2009.

Abstract

The tyrosine kinase, c-Abl, plays important roles in many aspects of cellular function. Previous reports showed that c-Abl is involved in NF-κB 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-κB and IRF3 activation. Taken together, our results suggest that c-Abl modulates innate immune response through MAVS.

Structured summary

MINT-7297498, MINT-7297511, MINT-7297557, MINT-7297574: MAVS (uniprotkb:Q7Z434) physically interacts (MI:0915) with c-Abl (uniprotkb:P00519) by anti tag coimmunoprecipitation (MI:0007)MINT-7297542: c-Abl (uniprotkb:P00519) physically interacts (MI:0915) with MAVS (uniprotkb:Q7Z434) by anti bait coimmunoprecipitation (MI:0006)MINT-7297526: c-Abl (uniprotkb:P00519) physically interacts (MI:0915) with MAVS (uniprotkb:Q7Z434) by far western blotting (MI:0047)