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NF-κB activation by TNFα in endothelial cells. TNFα binding to its receptor, TNF receptor (TNFR), activates NF-κB by parallel pathways. It signals through PI3Kγ to activate PKCζ, which triggers NADPH oxidase to produce ROS. ROS then causes phosphorylation and degradation of IκBα and liberates RelA/p65 for its nuclear translocation and DNA binding. TNFα also initiates RelA/p65 serine phosphorylation through PI3Kγ/PKCζ and PKCδ/p38 pathways, amplifying its transcriptional activity.
