Inhibition of glycogen synthase (casein) kinase-1 by divalent metal ions.
The specificity of glycogen synthase (casein) kinase-1 (CK-1) for different divalent metal ions was explored in this study. Of nine metal ions (Mg2+, Mn2+, Zn2+, Cu2+, Ca2+, Ba2+, Ni2+, Co2+, Fe2+) tested, only Mg2+ supported significant kinase activity. Several of the other metals, however, inhibited the Mg2+-stimulated kinase activity. Half-maximal inhibitions by Mn2+, Zn2+, Co2+, Fe2+, and Ni2+ were observed at 55, 65, 110, 125, and 284 microM, respectively. Kinetic analyses indicate that the metal ions are acting as competitive inhibitors of CK-1 with respect to the protein substrate (casein) and as noncompetitive inhibitors with respect to the nucleotide substrate (ATP). The inhibition of CK-1 by the different metal ions can be reversed by EGTA.
Singh
T J
TJ
Department of Biology, University of Waterloo, Ont., Canada.
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002413:Cations, Divalent / Q000494:pharmacology; D002417:Cattle; D007700:Kinetics; D008670:Metals / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D013379:Substrate Specificity
D002413:Cations, Divalent; D008670:Metals; D047428:Protein Kinase Inhibitors; D017871:Calcium-Calmodulin-Dependent Protein Kinases