Effects of cadmium on nuclear protein kinase C.
Cadmium is a carcinogen whose genotoxicity is only weak. Besides its tumor-initiating capacity, cadmium may be tumor-promoting, since it interferes with several steps of cellular signal transduction. We have investigated effects of cadmium(II) on protein kinase C (PKC), which is a key enzyme in the control of cellular growth and differentiation. Tumor-promoting phorbol esters cause an activation and translocation of PKC from the cytosol to the plasma membrane and to the nucleus of mammalian cells. In mouse 3T3/10 T 1/2 fibroblasts, cadmium(II) potentiated the effect of phorbol ester on nuclear binding and activation of PKC. Furthermore, in a reconstituted system consisting of rat liver nuclei and rat brain PKC, cadmium stimulated the binding of the enzyme to a 105-kDa protein. We propose a model in which cadmium(II) substitutes for zinc(II) in the regulatory domain of PKC, thus rendering the putative protein-protein binding site exposed. Further work is required to elucidate the potential role of the nuclear PKC binding protein(s) in the control of cell proliferation.
Department of Biology and Chemistry, University of Bremen, Germany.
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Beyersmann
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Block
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Malviya
D016475:3T3 Cells; D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D002467:Cell Nucleus / Q000187:drug effects* / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D011493:Protein Kinase C / Q000187:drug effects*; D051381:Rats; D015032:Zinc / Q000494:pharmacology
D002273:Carcinogens; D009687:Nuclear Proteins; D002104:Cadmium; D011493:Protein Kinase C; D015032:Zinc