Figure 2

A schematic diagram of the flow of information from the extracellular environment to the expression of target genes in the nucleus by the canonical IL-12 signaling network. These signaling networks originate at the cell membrane following the activation of dimers of the cytokine receptors, such as IL12Rβ 1-IL12Rβ 2. The yellow bars on the IL12Rβ 1 and IL12Rβ 2 receptors indicate the particular tyrosine residues within the intracellular portions of the receptors. In the mouse, STAT4 interacts primarily with the tyrosine residues Y₇₅₇, Y₈₀₄, and Y₈₁₁ on IL-12Rβ 2. The green bars indicate the BOX motifs that interact with the kinases: TYK2 and JAK2. The orange boxes correspond to canonical Janus Kinases, TYK2 and JAK2, that interact with the IL-12 receptor. Key signaling proteins within individual pathways are shown. The red lines indicate protein-protein interactions that negatively regulate this signaling network.