title: Role of cadmium in activating nuclear protein kinase C and the enzyme binding to nuclear protein.
abstract: Specific effects of cadmium on nuclear protein kinase C activity were found with 3T3/10T1/2 mouse fibroblast and rat liver nuclei. Treatment of the mouse fibroblasts in culture with 12-O-tetradecanoylphorbol-13-acetate resulted in the stimulation of nuclear protein kinase C activity in a "fixed" pool which is defined by its resistance to chelator extraction, whereas the chelator extractable enzyme activity, defined as the "labile" pool was unaffected. Cadmium was found to potentiate the effect of the phorbol ester, directed specifically to nuclei, since the particulate protein kinase C activity was not changed under similar treatment. In a reconstituted system consisting of rat liver nuclei and rat brain protein kinase C, cadmium stimulated the binding of the enzyme to a 105-kDa nuclear protein. The binding of a 105-kDa protein to protein kinase C is attributed strictly due to the cadmium effect, whereas a 50-kDa protein binding to protein kinase C was only enhanced by cadmium. We propose a mechanistic model, where cadmium substitutes zinc in the regulatory domain of protein kinase C rendering the putative protein-protein binding site exposed.
authors.affiliation: Laboratoire de Neurobiologie Moléculaire des Interactions Cellulaires, Centre de Neurochimie de Strasbourg, France.
authors.forename: C
authors.initials: C
authors.lastname: Block
authors.forename: S
authors.initials: S
authors.lastname: Freyermuth
authors.forename: D
authors.initials: D
authors.lastname: Beyersmann
authors.forename: A N
authors.initials: AN
authors.lastname: Malviya
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology; D002104:Cadmium / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology*; D004789:Enzyme Activation; D008099:Liver / Q000166:cytology; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D009687:Nuclear Proteins; D002104:Cadmium; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate