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Xiong, Yan; Luo, Dan-Ju; Wang, Xiu-Lian; Qiu, Mei; Yang, Yang; Yan, Xiong; Wang, Jian-Zhi; Ye, Qi-Fa; Liu, Rong
Neuroscience Bulletin/Neuroscience bulletin, 06/2015, Volume: 31, Issue: 3Journal Article
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.
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