FIGURE 3.

Cooperation of canonical and noncanonical activation pathways of IL‐22R. Schematic representation of the signalling cascade induced by IL‐22. The C‐terminal part of IL‐22R is pre‐associated with the coiled‐coil domain of STAT3. IL‐22 binds to IL‐22R leading to JAK transactivation. 1) Noncanonical STAT3 activation: Activated JAKs phosphorylate tyrosine residues on pre‐associated STAT3 leading to its activation, independently of receptor tyrosine residues. 2) Canonical STAT activation: Activated JAKs also phosphorylate tyrosine residues in the intracellular domain of the receptor. These phosphotyrosines serve as docking sites for STAT recruitment through their SH2 domains. Activated STATs form homo‐ and hetero‐dimers that migrate into the nucleus and regulate the transcription of specific genes.