Inteferons pen the JAK-STAT pathway

Upon binding to its dimeric receptor (IFNAR1 & IFNAR2), type I IFN promotes the apposition of two receptor associated JAKs (Jak1 & Tyk2), directing transphosphorylation and activation. The activated JAKs then phosphorylate receptor tyrosine(s), promoting a SH2 domain dependent recruitment of Stat1 and Stat2. At the receptor, Stat1 and Stat2 are activated by phosphorylation, they heterodimerizes, translocate into the nucleus, and associate with IRF-9 to from ISGF-3, which binds to ISREs to drive the expression of corresponding target genes. Only type I and type III IFNs signal through this pathway. IFN-γ directs the activation of a unique dimeric receptor (i.e., IFNGR1 & IFNGR2) by promoting the activation of two receptor associated JAKs (i.e., Jak1 and Jak2). These JAKs phosphorylate a single IFNGR1 tyrosine, which directs the SH2 domain dependent recruitment and activation of Stat1. Activated Stat1 homodimers translocate to the nucleus, bind to the members of the GAS family of enhancers and drive the expression of target genes. All four-helix bundle cytokines family, including type I and III IFNs transduce signals through this pathway.

Publication

Inteferons pen the JAK-STAT pathway. () Christian Schindler, et al. Semin Cell Dev Biol. ;19(4):311-318. Figure: F2. All organisms Mus musculus Ovis aries Homo sapiens Danio rerio Drosophila melanogaster

Disease mentions