Zinc induces protein phosphatase 2A （PP2A） inactivation and tau hyperphosphorylation through PP2A （tyrosine 307） phosphorylation in cells and the brain, but whether Zn2＋ has a direct inhibitory effect on PP2A is ...Zinc induces protein phosphatase 2A （PP2A） inactivation and tau hyperphosphorylation through PP2A （tyrosine 307） phosphorylation in cells and the brain, but whether Zn2＋ has a direct inhibitory effect on PP2A is not clear. Here we explored the effect of Zn2＋ on PP2A and their direct interaction in vitro. The results showed that Zn2＋ mimicked the inhibitory effect of okadaic acid on protein phosphatase and prevented tau dephosphorylation in N2a cell lysates. PP2A activity assays indicated that a low concentration （10 pmol/L） of Zn2＋ inhibited PP2A directly. Further Zn2＋-IDA-agarose affinity binding assays showed that Zn2＋ bound to and inhibited PP2Ac（51l-270） but not PP2Ac（1.50） or PP2Ac（27.309）. Taken together, Zn2＋ inhibits PP2A directly through binding to PP2Ac（51-270） in vitro.展开更多
基金supported by Natural Science Foundation of Hubei Province, China (2012FFA044, 2013CFB258)the National Natural Science Foundation of China (81271403, 81471304, 81261120570)
文摘Zinc induces protein phosphatase 2A （PP2A） inactivation and tau hyperphosphorylation through PP2A （tyrosine 307） phosphorylation in cells and the brain, but whether Zn2＋ has a direct inhibitory effect on PP2A is not clear. Here we explored the effect of Zn2＋ on PP2A and their direct interaction in vitro. The results showed that Zn2＋ mimicked the inhibitory effect of okadaic acid on protein phosphatase and prevented tau dephosphorylation in N2a cell lysates. PP2A activity assays indicated that a low concentration （10 pmol/L） of Zn2＋ inhibited PP2A directly. Further Zn2＋-IDA-agarose affinity binding assays showed that Zn2＋ bound to and inhibited PP2Ac（51l-270） but not PP2Ac（1.50） or PP2Ac（27.309）. Taken together, Zn2＋ inhibits PP2A directly through binding to PP2Ac（51-270） in vitro.
