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. 2015 Apr 8;31(3):331–337. doi: 10.1007/s12264-014-1519-z

Zinc binds to and directly inhibits protein phosphatase 2A in vitro

Yan Xiong 1,2, Dan-Ju Luo 2, Xiu-Lian Wang 2, Mei Qiu 2, Yang Yang 2, Xiong Yan 2, Jian-Zhi Wang 2, Qi-Fa Ye 1,4,✉, Rong Liu 2,3,✉
PMCID: PMC5563689  PMID: 25854679

Abstract

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 μmol/L) of Zn2+ inhibited PP2A directly. Further Zn2+-IDA-agarose affinity binding assays showed that Zn2+ bound to and inhibited PP2Ac(51–270) but not PP2Ac(1–50) or PP2Ac(271–309). Taken together, Zn2+ inhibits PP2A directly through binding to PP2Ac(51–270) in vitro.

Keywords: zinc, protein phosphatase 2A, direct inhibition

Contributor Information

Qi-Fa Ye, Email: yqf_china@163.com.

Rong Liu, Email: rong.liu@mail.hust.edu.cn.

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