The NF-kB/Rel transcription factors are present in the cytosol in an inactive state complexed with the inhibitory IkB proteins .Activation occurs via phosphorylation of IkBalpha at Ser32 and Ser36 followed by proteasome-mediated degradation that results in the release and nuclear translocation of active NF-kB . IkBalpha 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.The regulation of IkBbeta and IkBE is similar to that of IkBalpha. However, the phosphorylation and ubiquitin-mediated degradation of these proteins occurs with much slower kinetics. IKK phosphorylation of IkBbeta occurs at Ser19 and Ser23, while IkBE can be phosphorylated at Ser18 and Ser22 .