The NF-?B/Rel transcription factors are present in the cytosol in an inactive state complexed with the inhibitory I?B proteins . Activation occurs via phosphorylation of I?B? at Ser32 and Ser36 followed by proteasome-mediated degradation that results in the release and nuclear translocation of active NF-?B . I?B? 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 I?B at these activating sites have been identified .