Fig. 7.

A schematic diagram of IRAK activation within the Myddosome shown here for the IL-1 receptors. Upon ligand binding, IL-1 receptor (IL-1R) and IL-1 receptor accessary protein (IL-1RAcp) recruit MyD88, which in turn recruits the upstream kinase IRAK4 and then the downstream kinase IRAK1 or IRAK2. IRAK4 recruitment leads to increased local concentration of the kinase domain, leading to its dimerization and trans-autophosphorylation. Phosphorylated IRAK4 dissociates from the dimer to interact with and phosphorylate IRAK1 or IRAK2, leading to the first step of its activation.