Cell signaling pathways activated by TNF. TNFR1 activation leads to recruitment of intracellular adaptor proteins (TRADD, FADD, TRAF, and RIP), which activate multiple signal transduction pathways. TNFR sequentially recruits TRADD, TRAF2, RIP, TAK1, and IKK, leading to the activation of NF-κB³¹ ; and the recruitment of TRADD, FADD, and caspase-8, leads to the activation of caspase-3, which in turn induces apoptosis.²⁸  JNK is activated through the sequential recruitment of TRAF2, RIP, MEKK1, and MKK7.⁷⁹  Exposure of cells to TNFα in most cases results in the generation of reactive oxygen species, leading to activation of MKK7 and JNK.²⁹  The activation of ERK and p38MAPK is via TRADD, TRAF2, RIP, TAK1, and MKK3/6.⁸⁰