Effect of Zinc on Calmodulin‐Stimulated Protein Kinase II and Protein Phosphorylation in Rat Cerebral Cortex

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Abstract
The effect of increasing concentrations of Zn2+ (1 μM‐5 mM) on protein phosphorylation was investigated in cytosol (S3) and crude synaptic plasma membrane (P2‐M) fractions from rat cerebral cortex and purified calmodulinstimulated protein kinase II (CMKII). Zn2+ was found to be a potent inhibitor of both protein kinase and protein phosphatase activities, with highly specific effects on CMK II. Only one phosphoprotein band (40 kDa in P2‐M phosphorylated under basal conditions) was unaffected by addition of Zn2+. The vast majority of phosphoprotein bands in both basal and calcium/calmodulin‐stimulated conditions showed a dose‐dependent inhibition of phosphorylation, which varied with individual phosphoproteins. Two basal phosphoprotein bands (58 and 66 kDa in S3) showed a significant stimulation of phosphorylation at 100 μM Zn2+ with decreased stimulation at higher concentrations, which was absent by 5 mM Zn2+. A few Ca2+/calmodulin‐stimulated phosphoproteins in P2‐M and S3 showed biphasic behavior inhibition at 100 μM that produces a redistribution of activity biased toward autophosphorylation and an subunit with an altered mobility on sodium dodecyl sulfate‐containing gels.