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. Author manuscript; available in PMC: 2022 Sep 14.
Published in final edited form as: Immunity. 2021 Sep 14;54(9):1915–1932. doi: 10.1016/j.immuni.2021.08.018

Figure 2. Molecular mechanisms for combinatorial encoding to achieve stimulus-specific responses.

Figure 2.

A-D. Pathway branching, in which one upstream protein activates multiple downstream signaling mediators, can occur at several signaling layers. Examples include branching (A) at the level of receptors with TLR4 activating the MyD88 and TRIF pathway, (B) at the level of adaptors with TRIF, MAVS, and STING being capable of IRF3 and NFκB activation, (C) at the level of ubiquitin chains, which scaffold activation of TAK1 for MAPK activation and of IKK for NFκB activation, and (D) at the level of kinase cascades which branch to activate IKK and the MAPKs p38, JNK, and ERK.

E. Combinatorial coding in the innate immune network is mediated by receptor-specific utilization of adapters and pathway branching at the adapter layer.