Hozaifa Metwally, Maha M Elbrashy, Tatsuhiko Ozawa, Kazuki Okuyama, Jason T White, Janyerkye Tulyeu, Jonas Nørskov Søndergaard, James Badger Wing, Arisa Muratsu, Hisatake Matsumoto, Masahito Ikawa, Hiroyuki Kishi, Ichiro Taniuchi, Tadamitsu Kishimoto
Since its discovery over three decades ago, signal transducer and activator of transcription 1 (STAT1) has been extensively studied as a central mediator for interferons (IFNs) signaling and antiviral defense. Here, using genetic and biochemical assays, we unveil Thr748 as a conserved IFN-independent phosphorylation switch in Stat1, which restricts IFN signaling and promotes innate inflammatory responses following the recognition of the bacterial-derived toxin lipopolysaccharide (LPS). Genetically engineered mice expressing phospho-deficient threonine748-to-alanine (T748A) mutant Stat1 are resistant to LPS-induced lethality...
April 23, 2024: Proceedings of the National Academy of Sciences of the United States of America