Figure 3. IL-17RA/RB signaling.
Upon IL-17E binding to its receptor, homotypic interactions between the SEFIR domains in the receptor and in the adapter Act1/CIKS are established. This leads to the recruitment of TRAF6, activating the MAPK and NF-κB signaling pathways. In turn, Act1 can recruit TRAF4, which activates the E3 ligase SMURF2. This leads to the ubiquitylation and subsequent degradation of the inhibitor DAZAP2, amplifying IL-17E-mediated signaling. In addition, IL-17RB can elicit STAT5 activation in an Act1-independent manner.