The results suggest that the amino-terminal fragment suppresses neurite outgrowth by competing for plasma membrane binding.
These observations suggested that 14-3-3zeta may be bound to GSK3Beta and/or tau within brain microtubules and may be a component of tau phosphorylation complex.Therefore, 14-3-3 must be the central molecule that holds tau and GSK3Beta within the complex. Indeed, FLAG-tau co-immunoprecipitated with HA-GSK3Beta from cells overexpressing FLAG-tau and HA-GSK3Beta only when these cells also overexpressed Xpress-14-3-3zeta (Fig. 6A, lanes 8 and 9), indicating that GSK3Beta associates with tau only in the presence of 14-3-3zeta. As discussed above, 14-3-3zeta binds to tau (36) and GSK3Beta (Fig. 5) directly. Taken together, these observations indicated that 14-3-3zeta connects GSK3Beta to tau in vivo.
In cells that were co-transfected with fixed amounts of FLAG-tau and HA-GSK3Beta but different amounts of Xpress-14-3-3zeta, FLAG-tau phosphorylation increased progressively with the increase in the amount of Xpress-14-3-3zeta (lanes 7–9). This increase was evident not only by an increased immunoreactivity against all tau phosphorylation-sensitive antibodies tested but also by a retarded mobility of FLAG-tau on the SDS gel, a characteristic feature of hyperphosphorylated tau (2, 3). Thus, 14-3-3zeta profoundly stimulated GSK3Beta-catalyzed tau phosphorylation in vivo.
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.