I kappa B kinase alpha (IKK alpha) regulation of IKK beta kinase activity

Two related kinases, I kappa B kinase alpha (IKK alpha) and IKK beta, phosp horylate the I kappa B proteins, leading to their degradation and the subse quent activation of gene expression by NF-kappa B. IKK beta has a much high er level of kinase activity for the I kappa B proteins than does IKK alpha and is more critical than IKK alpha in modulating tumor necrosis factor alp ha activation of the NF-kappa B pathway. These results indicate an importan t role for IKK beta in activating the NF-kappa B pathway but leave open the question of the role of IKK alpha in regulating this pathway. In the curre nt study, we demonstrate that IKK alpha directly phosphorylates IKK beta. M oreover, IKK alpha either directly or indirectly enhances IKK beta kinase a ctivity for I kappa B alpha. Finally, transfection studies to analyze NF-ka ppa B-directed gene expression suggest that IKK alpha is upstream of IKK be ta in activating the NF-kappa B pathway. These results indicate that IKK al pha, in addition to its previously described ability to phosphorylate I kap pa B alpha, can increase the ability of IKK beta to phosphorylate I kappa B alpha.