Casein kinase II from Caenorhabditis elegans. Properties and developmental regulation of the enzyme; cloning and sequence analyses of cDNA and the gene for the catalytic subunit

The nematode Caenorhabditis elegans provides a model system for investigating the structure, function, and regulation of casein kinase II. Cytosols from C. elegans embryos and gravid adults, which contain fertilized eggs and embryos, are enriched in casein kinase II activity; cytosols from newly hatched larva, four subsequent larval stages, and immature adults exhibit casein kinase II levels that are 3-10-fold lower than those observed in embryo cytosol. C. elegans casein kinase II contains α (M(r) = 42,000) and β (M(r) = 29,000) subunits and has a Stokes radius of 50 nm. The enzyme utilizes ATP and GTP as substrates, is potently inhibited by heparin and undergoes autophosphorylation. Sequence analyses of cloned cDNAs corresponding to the 1.7-kilobase mRNA encoding the α (catalytic) subunit of casein kinase II indicate that the α polypeptide contains 359 amino acid residues. Variations in the abundance of casein kinase IIα mRNA are coordinated with changes in enzyme activity during C. elegans development, indicating that α subunit expression is controlled at a pretranslational level. However, the magnitude of the developmentally controlled changes in phosphotransferase activity exceeded the corresponding increments in α subunit mRNA content. This suggests that translational and/or post-translational mechanism also play an important role in the developmental regulation of C. elegans casein kinase II activity. The 2.9-kilobase casein kinase IIα gene is divided into eight exons by intervening sequences ranging from 48 to 457 base pairs in length. The α gene promoter contains a TATA box, and a unique transcription start site has been identified. The intron/exon organization of the casein kinase IIα gene differs markedly from the gene structure of the catalytic subunit of murine cAMP-dependent protein kinase (Chrivia, J.C., Uhler, M.D., and McKnight, G.S. (1988) J. Biol. Chem. 263, 5739-5744).