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. 2019 May 16;10:1107. doi: 10.3389/fimmu.2019.01107

Figure 5.

Figure 5

MAPK pathways downstream of TRAF6. MAPK pathways are regulated by the phosphorylation cascade of MAP3Ks, MAPKKs, and MAPKs, resulting in the activation of MKs and a transcription factor AP-1. TRAF6 mediates the activation of MAP3Ks that are mainly involved in p38 and JNK MAPK activation. TRAF6 activates ASK1 MAP3K under oxidative stresses by removing thioredoxin. TRAF6-mediated K63-linked ubiquitin chains recruit TAB2/3 and subsequent activation of TAK1, which is also involved in the activation of NF-κB pathways. ASK1 and TAK1 are involved in the activation of p38 MAPK. p38 regulates gene expression at both transcriptional and post-transcriptional levels. C/EBP is a major transcription factor downstream of p38 MAPK. The E3 ligase activity of TRAF6 is required for the activation of other MAP3Ks MEKK3 and MEKK1, which are mainly involved in the activation of JNK MAPK, resulting in AP-1-mediated gene transcription. AP-1, activator protein 1; ASK1, apoptosis signal-regulating kinase 1; ERK, extracellular signal-regulated kinase; JNK, c-Jun N-terminal kinase; MAPK, mitogen-activated protein kinase; MAPKK, MAPK kinase; MAP3K, MAPK kinase kinase; MEKK; MAPK/ERK kinase kinase; MK, MAPK-activated protein kinase; MKK, MAPK kinase; MNK, MAPK-interacting kinase; MSK, mitogen- and stress-activated kinase; NF-κB; ROS, reactive oxygen species; NF-κB, nuclear factor κB; TAB, TAK1 binding protein; TAK1, TGF-β-activated kinase 1; TRAF6, tumor necrosis factor receptor associated factor 6; Trx, thioredoxin.