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  Indian J Med Microbiol
 

Figure 1: The JNK signaling pathway. Inflammatory cytokines, danger-associated molecular patterns and pro-fibrotic growth factors can induce phosphorylation/activation of enzymes in the MAP3K family. MAP3K enzymes then activate MAP2K4 and MAP2K7 which directly phosphorylate and active JNK. In addition, JNK is highly susceptible to activation by ROS; this operates via ROS activation of MAP3K5. Activated JNK can induce cell apoptosis by causing cytochrome c release by mitochondria and by necroptosis via activation of the RIPK3/MLKL pathway. In the nucleus, activated JNK can phosphorylate the amino terminus of JUN to activate the transcription factor AP1 which transcribes gene involved in the inflammatory and fibrotic responses. In addition, activated JNK can phosphorylate the linker region of SMAD3 to enhance TGF-β1-induced transcription of profibrotic factors. This diagram is reproduced with permission based on an earlier publication of the same authors.[6] JNK: JUN amino terminal kinase, MAP3K: Mitogen-activated protein kinase kinase kinase, ROS: Reactive oxygen species, RIPK3: Receptor interacting serine/threonine kinase 3, MLKL: Mixed lineage kinase domain-like pseudokinase, AP1: Activator protein 1, SMAD3: Mothers against decapentaplegic homolog 3, TGF-β1: Transforming growth factor-beta 1

Figure 1: The JNK signaling pathway. Inflammatory cytokines, danger-associated molecular patterns and pro-fibrotic growth factors can induce phosphorylation/activation of enzymes in the MAP3K family. MAP3K enzymes then activate MAP2K4 and MAP2K7 which directly phosphorylate and active JNK. In addition, JNK is highly susceptible to activation by ROS; this operates via ROS activation of MAP3K5. Activated JNK can induce cell apoptosis by causing cytochrome c release by mitochondria and by necroptosis via activation of the RIPK3/MLKL pathway. In the nucleus, activated JNK can phosphorylate the amino terminus of JUN to activate the transcription factor AP1 which transcribes gene involved in the inflammatory and fibrotic responses. In addition, activated JNK can phosphorylate the linker region of SMAD3 to enhance TGF-β1-induced transcription of profibrotic factors. This diagram is reproduced with permission based on an earlier publication of the same authors.<sup>[6]</sup> JNK: JUN amino terminal kinase, MAP3K: Mitogen-activated protein kinase kinase kinase, ROS: Reactive oxygen species, RIPK3: Receptor interacting serine/threonine kinase 3, MLKL: Mixed lineage kinase domain-like pseudokinase, AP1: Activator protein 1, SMAD3: Mothers against decapentaplegic homolog 3, TGF-β1: Transforming growth factor-beta 1