Beryllium toxicity. The selective inhibition of casein kinase 1.
1. Cyclic AMP-independent casein kinase 1 in liver cytoplasm and nuclei was inhibited by Be2+ in vitro (Ki 2.5 microM and 29 microM respectively). Casein kinase 2 (phosvitin kinase) and cyclic AMP-dependent protein kinase were unaffected. 2. The inhibition of casein kinase 1 by Be2+ was competitive with respect to the protein substrate; at non-saturating concentrations of casein, inhibition was non-competitive with respect to ATP. 3. In rats given LD50 doses of Be2+ 24 h before death, the activities of cytoplasmic and nuclear casein kinase 1 in livers from partially hepatectomized animals were diminished approx. 50%; with intact rats, nuclear casein kinase 1 was inhibited at concentrations of casein less than the Km.
D000818:Animals; D001608:Beryllium / Q000494:pharmacology*; D047388:Casein Kinases; D002417:Cattle; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology; D003593:Cytoplasm / Q000187:drug effects / Q000201:enzymology; D004591:Electrophoresis, Polyacrylamide Gel; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D047428:Protein Kinase Inhibitors; D051381:Rats
D047428:Protein Kinase Inhibitors; D047388:Casein Kinases; D001608:Beryllium