FIGURE 8:

Overview of Jak-binding sites within the IL-23 receptor complex. Formation of the IL-23 receptor complex consisting of p19, p40, IL-23R, and IL-12Rβ1 results in the activation of signaling pathways (Floss et al., 2015), and interaction of Janus kinases with the intracellular domains of the receptors initiates signaling cascades. According to Kotenko et al. (1996), IL-23R represents the signal transducer (ST) with a Janus kinase association site (JAS) and STAT recruitment sites (SRS). IL-12Rβ1 is regarded as a helper receptor (HR), which contains Box1 and Box2 motifs for association of the protein tyrosine kinase (PTK) Tyk2 or Jak1 and no SRS. Tyrosines within the IL-23R cytoplasmic domain are highlighted in black (Y416, Y504, Y542, and Y626, involved in IL-23 signaling) and white (Y448, Y469, and Y496). Postulated JAS I403-E417 is indicated (Pidasheva et al., 2011). Experimentally validated JAS E455-E479 is highlighted. Amino acid sequences that might influence kinase activity are designated.