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.
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Xiong, Y., Luo, DJ., Wang, XL. et al. Zinc binds to and directly inhibits protein phosphatase 2A in vitro . Neurosci. Bull. 31, 331–337 (2015). https://doi.org/10.1007/s12264-014-1519-z
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DOI: https://doi.org/10.1007/s12264-014-1519-z