The NF-κB/Rel transcription factors are present in the cytosol in an inactive state complexed with the inhibitory IKB proteins. Activation occurs via phosphorylation of IKB-α at Ser32 and Ser36 followed by proteasome-mediated degradation that results in the release and nuclear translocation of active NF-κB. IKBα phosphorylation and resulting Rel-dependent transcription are activated by a highly diverse group of extracellular signals including inflammatory cytokines, growth factors, and chemokines. Kinases that phosphorylate IKB at these activating sites have been identified.