Glycogen synthase kinase-3 beta-mediated tau phosphorylation in cultured cell lines

To study further the role of glycogen synthase kinase-3beta on tau phosphorylation, glycogen synthase kinase-3beta and tau expression vectors were co-transfected into CHO-K1, COS-7 and SH-SY5Y cell. Tau phosphorylation was assessed by phosphorylation-dependent antibodies AT-8, AT-180, AT-270 and PHF-1. The AT-270 and AT-8 epitopes were consistently phosphorylated by glycogen synthase kinase-3beta in the three cell lines. Phosphorylation on AT-180 epitope was significant in CHO-K1 and SH-SY5Y cells while PHF-1 epitope was hyper-phosphorylated only in SH-SY5Y cells. We also found that lithium induces phosphorylation of the serine 9 residue of glycogen synthase kinase-3beta together with inhibition of tau phosphorylation on PHF-1 epitope in all the three cell lines. This suggests a novel mechanism whereby lithium-mediated inhibition of GSK-3beta activity influences tau phosphorylation.