Type I IFN Signaling

Type I IFN Signaling. Type-I IFNs bind to a heterodimer composed of the transmembrane receptor subunits IFNAR1 and IFNAR2, which results in activation of the receptor-associated kinases Jak1 and Tyk2. In the canonical signaling pathway, the cytoplasmic signal transducers and activator of transcription (Stat) proteins are recruited to the receptor docking sites, phosphorylated, and dimerize to form the active transcription factors ISGF3 (Interferon stimulated gene factor 3), composed of phosphorylated Stat 1 and Stat2, and IRF9 (p48/ISGF3γ), and AAF/GAF (alpha activation factor/gamma activation factor), which is composed of two phosphorylated subunits of Stat1. These induce transcription of hundreds of interferon-stimulated genes (ISGs). IFN treatment also leads to induction of other non-canonical signaling pathways, including those involving p38 MAPK, Akt, and Crk. Upstream signaling from the IFNR complex leads to p38 phosphorylation, which modulates IFN activity and leads to growth inhibition of cells. CrkL and CrkII are tyrosine phosphorylated by Tyk2 after IFN treatment, and CrkL can also form transcription factor complexes with phosphorylated Stat5. Signaling pathways downstream of PI3K, involving Akt and mTOR, or PKCδ, are also important in mediating the biological activities of IFN.

Publication

Antiproliferative Properties of Type I and Type II Interferon. (2010) Joseph Bekisz, et al. Pharmaceuticals (Basel). 2010 Apr;3(4):994-1015. Figure: F1. All organisms Mus musculus Homo sapiens Oryctolagus cuniculus Danio rerio

Disease mentions