Takayoshi Shirasaki, Satoshi Yamagoe, Tetsuro Shimakami, Kazuhisa Murai, Ryu Imamura, Kiyo-Aki Ishii, Hiroaki Takayama, Yukako Matsumoto, Natsumi Tajima-Shirasaki, Naoto Nagata, Ryogo Shimizu, Souma Yamanaka, Atsushi Abe, Hitoshi Omura, Kazunori Kawaguchi, Hikari Okada, Taro Yamashita, Tomoki Yoshikawa, Kazuhiro Takimoto, Motoko Taharaguchi, Shogo Takatsuka, Yoshitsugu Miyazaki, Toshikatsu Tamai, Yamato Tanabe, Makoto Kurachi, Yasuhiko Yamamoto, Shuichi Kaneko, Kunio Matsumoto, Toshinari Takamura, Masao Honda
Retinoic acid-inducible gene (RIG)-I is an essential innate immune sensor that recognises pathogen RNAs and induces interferon (IFN) production. However, little is known about how host proteins regulate RIG-I activation. Here, we show that leukocyte cell-derived chemotaxin 2 (LECT2), a hepatokine and ligand of the MET receptor tyrosine kinase is an antiviral regulator that promotes the RIG-I-mediated innate immune response. Upon binding to MET, LECT2 induces the recruitment of the phosphatase PTP4A1 to MET and facilitates the dissociation and dephosphorylation of phosphorylated SHP2 from MET, thereby protecting RIG-I from SHP2/c-Cbl-mediated degradation...
June 8, 2022: Nature Communications