title: Zinc binds to and directly inhibits protein phosphatase 2A in vitro.
abstract: Zinc induces protein phosphatase 2A (PP2A) inactivation and tau hyperphosphorylation through PP2A (tyrosine 307) phosphorylation in cells and the brain, but whether Zn(2+) has a direct inhibitory effect on PP2A is not clear. Here we explored the effect of Zn(2+) on PP2A and their direct interaction in vitro. The results showed that Zn(2+) 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 Zn(2+) inhibited PP2A directly. Further Zn(2+)-IDA-agarose affinity binding assays showed that Zn(2+) bound to and inhibited PP2Ac(51-270) but not PP2Ac(1-50) or PP2Ac(271-309). Taken together, Zn(2+) inhibits PP2A directly through binding to PP2Ac(51-270) in vitro.
authors: Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan University, Wuhan, 430071, China.
authors: Yan
authors: Y
authors: Xiong
authors: Dan-Ju
authors: DJ
authors: Luo
authors: Xiu-Lian
authors: XL
authors: Wang
authors: Mei
authors: M
authors: Qiu
authors: Yang
authors: Y
authors: Yang
authors: Xiong
authors: X
authors: Yan
authors: Jian-Zhi
authors: JZ
authors: Wang
authors: Qi-Fa
authors: QF
authors: Ye
authors: Rong
authors: R
authors: Liu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D066298:In Vitro Techniques; D051379:Mice; D019319:Okadaic Acid / Q000494:pharmacology; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015032:Zinc / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D019319:Okadaic Acid; D054648:Protein Phosphatase 2; D015032:Zinc