P70 S6 kinase mediates tau phosphorylation and synthesis |
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| Authors: | Pei Jin-Jing An Wen-Lin Zhou Xin-Wen Nishimura Takeshi Norberg Jan Benedikz Eirikur Götz Jürgen Winblad Bengt |
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| Affiliation: | Department of Neurotec, Division of Experimental Geriatrics, Karolinska Institutet, KFC Novum, Plan 4, SE-141 86, Huddinge, Sweden. Jin-Jing.Pei@neurotec.ki.se |
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| Abstract: | Currently, we found that the 70-kDa p70 S6 kinase (p70S6K) directly phosphorylates tau at S262, S214, and T212 sites in vitro. By immunoprecipitation, p-p70S6K (T421/S424) showed a close association with p-tau (S262 and S396/404). Zinc-induced p70S6K activation could only upregulate translation of total S6 and tau but not global proteins in SH-SY5Y cells. The requirement of p70S6K activation was confirmed in the SH-SY5Y cells that overexpress wild-type htau40. Level of p-p70S6K (T421/S424) was only significantly correlated with p-tau at S262, S214, and T212, but not T212/S214, in Alzheimer's disease (AD) brains. These suggested that p70S6K might contribute to tau related pathologies in AD brains. |
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| Keywords: | AD, Alzheimer’s disease PHFs, paired helical filaments NFT, neurofibrillary tangle p70S6K, the 70-kDa p70 S6 kinase mTOR, mammalian target of rapamycin PI3K, phosphoinositol 3-kinase MAPK, mitogen-activated protein kinase ELISA, enzyme-linked immunosorbent assay 5′UTR, the 5′ untranslated region CaMKII, calcium/calmodulin-dependent protein kinase II MARK, microtubule-affinity regulating kinase 5′TOP, 5′-terminal oligopyrimidine tract |
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