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.
Beyersmann
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Department of Biology and Chemistry, University of Bremen, Germany.
Block
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C
Malviya
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AN
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