CENTRAL OF I-KAPPA-B-ALPHA PROTEOLYSIS BY SITE-SPECIFIC, SIGNAL-INDUCED PHOSPHORYLATION

I kappa B-alpha inhibits transcription factor NF-kappa B by retaining it in the cytoplasm. Various stimuli, typically those associated with stress or pathogens, rapidly inactivate I kappa B-alpha. This liberate s NF-kappa B to translocate to the nucleus and initiate transcription of genes important for the defense of the organism. Activation of NF-k appa B correlates with phosphorylation of I kappa B-alpha and requires the proteolysis of this inhibitor. When either serine-32 or serine-36 of I kappa B-alpha was mutated, the protein did not undergo signal-in duced phosphorylation or degradation, and NF-kappa B could not be acti vated. These results suggest that phosphorylation at one or both of th ese residues is critical for activation of NF-kappa B.