Meta-Biol

• Pathways

Tyrosine-protein kinase JAK1 (JAK1) and Non-receptor tyrosine-protein kinase TYK2 (TYK2) are phosphorylated after Interferon lambda-1 (IFNL1, IL29) interacts with its receptor complex, which consists of Interferon lambda receptor-1 (IFNLR1 (class II cytokine receptor)), JAK1, Interleukin-10 receptor beta (IL10RB) and TYK2 (Novak et al.2008, Dumoitier et al. 2004).This initiates a signaling cascade that involves Jak1 and Tyk2 dependent tyrosine phosphorylation of signal transducers and activators of transcription 1 (STAT1) and STAT2 proteins that interact with a third protein, the p48 DNA binding subunit, to form the IFN stimulated gene factor 3 complex (ISGF3). This is a black box event since direct evidence for JAK1 and TYK2 binding after IFNL1 stimulation is lacking. However, this can be inferred from other cytokine signaling. In other cytokine ligand receptor cascades such as IFNalpha signaling, STAT activation occurs after phosphorylation by kinases associated with the receptor (Sheppard et al. 2003).