Casein kinase II phosphorylates Ser(468) in the PEST domain of the Drosophila I kappa B homologue cactus

Cactus protein is a Drosophila homologue of the mammalian I kappa B family of cytoplasmic anchor proteins. In unstimulated cells they function to retain rel/NF kappa B transcription factors in the cytoplasm but are rapidly degraded in response to signalling. The destruction of cactus or I kappa B alpha allows the rel/ NF kappa B transcription factor to relocalise to the nucleus. Cactus is a phosphoprotein and has in its C-terminus a PEST protein stability domain. In this paper we show that, like mammalian I kappa B alpha, the PEST domain of cactus is phosphorylated by casein kinase II. We have localised the site of modification to a single residue, Ser(468), and find no evidence for additional phosphorylation sites. The conservation of these sites in mammalian and invertebrate cytoplasmic anchor proteins suggests that phosphorylation by casein kinase II may play a critical functional role, plausibly in the regulation of constitutive or inducible proteolysis.