P70 S6 kinase mediates tau phosphorylation and synthesis

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.