Met receptor is essential for MAVS-mediated antiviral innate immunity in epithelial cells independent of its kinase activity

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 120; no. 40; p. e2307318120
• Main Authors: Imamura, Ryu, Sato, Hiroki, Chih-Cheng Voon, Dominic, Shirasaki, Takayoshi, Honda, Masao, Kurachi, Makoto, Sakai, Katsuya, Matsumoto, Kunio
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 03.10.2023
• Series: Brief Report
• Subjects: Biological Sciences; Cytokines; Epithelial Cells; Immunity, Innate; Receptor Protein-Tyrosine Kinases; RIG-I; MAVS; inflammatory cytokine; met receptor; RNA virus
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.2307318120

Epithelial tissue is at the forefront of innate immunity, playing a crucial role in the recognition and elimination of pathogens. Met is a receptor tyrosine kinase that is necessary for epithelial cell survival, proliferation, and regeneration. Here, we showed that Met is essential for the induction of cytokine production by cytosolic nonself double-stranded RNA through retinoic acid-inducible gene-I-like receptors (RLRs) in epithelial cells. Surprisingly, the tyrosine kinase activity of Met was dispensable for promoting cytokine production. Rather, the intracellular carboxy terminus of Met interacted with mitochondrial antiviral-signaling protein (MAVS) in RLR-mediated signaling to directly promote MAVS signalosome formation. These studies revealed a kinase activity-independent function of Met in the promotion of antiviral innate immune responses, defining dual roles of Met in both regeneration and immune responses in the epithelium.