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

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 mitochon-drial antiviral-signaling protein (MAVS) in RLR-mediated signaling to directly promote MAVS signalosome formation. These studies revealed a kinase activity-independent func-tion of Met in the promotion of antiviral innate immune responses, defining dual roles of Met in both regeneration and immune responses in the epithelium.

Automated summary

Met in epithelial tissue plays a crucial role in cytokine production, and its tyrosine kinase activity is not required for this process. The interaction between the intracellular carboxy terminus of Met and MAVS in RLR-mediated signaling promotes immune responses.