CONSTITUTIVE PHOSPHORYLATION OF I-KAPPA-B-ALPHA BY CASEIN KINASE-II

The NF-kappa B/Rel proteins are sequestered in the cytoplasm in associ ation with the phosphorylated form of I kappa B alpha. Upon induction with a wide variety of agents, the activity of NF-kappa B/Rel proteins is preceded by the rapid degradation of I kappa B alpha protein. We r eport the identification and partial purification of a cellular kinase from unstimulated or stimulated murine cells, which specifically phos phorylates the C terminus of I kappa B alpha. There are several consen sus sites for casein kinase II (CKII) in the C-terminal region of I ka ppa B alpha. Additionally, the activity of the cellular kinase is bloc ked by antibodies against the alpha subunit of CKII. No phosphorylatio n of the C-terminal region of I kappa B alpha can be detected if the f ive possible serine and threonine residues that can be phosphorylated by CKII are mutated to alanine. A two dimensional tryptic phosphopepti de map of I kappa B alpha from unstimulated cells was identical to tha t obtained by in vitro phosphorylation of I kappa B alpha with the par tially purified cellular kinase. We propose that constitutive phosphor ylation of I kappa B alpha is carried out by CKII.