Increasing evidence indicates that calmodulin, the ubiquitous Ca2+-binding protein in eukaryotes, serves as a major intracellular Ca2+ receptor regulating the activity or rate of many key enzymes and cellular processes, including a potential role in cell proliferation. Certain heavy metals are highly toxic to the cell; preliminary findings from our laboratory suggest that these metals effectively substitute for Ca2+ in calmodulin. Activation of calmodulin by these metals could upset its normal regulation by the cellular flux of Ca2+. Perhaps this could constitute in part a basis for the toxicity of these metals in cell physiology.
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