Affiliations: [a] Karolinska Institutet, KI-Alzheimer Disease Research Center (KI-ADRC), Novum, Huddinge, Sweden | [b] Department of Pathology and Molecular Biology, Guiyang Medical University, Guiyang, Guizhou, P. R. of China
Correspondence:
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Corresponding author: Jin-Jing Pei, MD., Ph.D., Karolinska Institutet, KI-Alzheimer Disease Research Center (KI-ADRC), Novum Plan 5, Novum, S-141 57, Huddinge, Sweden. Tel.: +46 8 585 83649; Fax: +46 8 585 83880; E-mail: Jin-Jing.Pei@ki.se.
Abstract: In this study, we investigated how tau phosphorylation is regulated by protein kinase glycogen synthase kinase 3β (GSK3β), protein kinase B (PKB), and protein phosphatase 2A (PP2A) in mouse N2a neuroblastoma cells. Results showed that GSK3β overexpression significantly increased PKB phosphorylation at the S473 site but not the T308 site. Neither GSK3β nor PKB overexpression could reduce the PP2AC phosphorylation at the Y307 site. In contrast, either PKB or GSK3β knockdown could increase PP2A phosphorylation at the Y307 site. PP2AC knockdown increased GSK3β phosphorylation at the S9 site but not at the Y216 site, and PKB phosphorylation at the T308 site but not at the S473 site. Tau phosphorylation at the S396 site was increased by GSK3β or PKB overexpression. Tau phosphorylation at the S214 site was only induced by PKB overexpression in the study. While GSK3β knockdown decreased tau phosphorylation at the S396 site, PKB knockdown increased tau phosphorylation at both the S396 and S214 sites. PP2AC knockdown decreased tau phosphorylation at the S396 and S214 sites. These findings suggest that tau phosphorylation at the S396 and S214 sites is differentially regulated by GSK3β, PKB, and PP2A in N2a cells. The final phosphorylation state of tau is possibly caused by the synergic action of the three enzymes.
Keywords: Glycogen synthase kinase 3β, protein kinase B, protein phosphatase 2A, tau
