Nuclear transcription factors of the NF-kappa B/Rel family are inhibited by I kappa B proteins, which inactivate NF-kappa B by trapping it in the cell cytoplasm. Phosphorylation of I kappa Bs marks them out for destruction, thereby relieving their inhibitory effect on NF-kappa B. A cytokine-activated protein kinase complex, IKK (for I kappa B kinase), has now been purified that phosphorylates I kappa Bs on the sites that trigger their degradation. A component of IKK was molecularly cloned and identified as a serine kinase. IKK turns out to be the long-sought-after protein kinase that mediates the critical regulatory step In NF-kappa B activation.