The IκB kinase complex in NF-κB regulation and beyond

The I kappa B kinase (IKK) complex is the signal integration hub for NF-kappa B activation. Composed of two serine-threonine kinases (IKK alpha and IKK beta) and the regulatory subunit NEMO (also known as IKK gamma), the IKK complex integrates signals from all NF-kappa B activating stimuli to catalyze the phosphorylation of various I kappa B and NF-kappa B proteins, as well as of other substrates. Since the discovery of the IKK complex components about 15 years ago, tremendous progress has been made in the understanding of the IKK architecture and its integration into signaling networks. In addition to the control of NF-kappa B, IKK subunits mediate the crosstalk with other pathways, thereby extending the complexity of their biological function. This review summarizes recent advances in IKK biology and focuses on emerging aspects of IKK structure, regulation and function.