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Assay for Phosphorylation and Microtubule Binding Along with Localization of Tau Protein in Colorectal Cancer Cells
Published on: October 10, 2017
P70 S6 kinase mediates tau phosphorylation and synthesis
Jin-Jing Pei1, Wen-Lin An, Xin-Wen Zhou
1Department of Neurotec, Division of Experimental Geriatrics, Karolinska Institutet, KFC Novum, Plan 4, SE-141 86, Huddinge, Sweden. Jin-Jing.Pei@neurotec.ki.se
FEBS Letters
|December 21, 2005
Summary
The 70-kDa p70 S6 kinase (p70S6K) phosphorylates tau protein, a key factor in Alzheimer's disease (AD) pathology. This kinase activation is linked to tau phosphorylation and may contribute to AD-related brain changes.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Tau protein phosphorylation is a hallmark of Alzheimer's disease (AD).
- The specific kinases involved in tau phosphorylation in AD remain an area of active investigation.
- p70 S6 kinase (p70S6K) is a key regulator of protein synthesis and cell growth.
Purpose of the Study:
- To investigate the direct role of p70 S6 kinase (p70S6K) in tau phosphorylation.
- To explore the association between activated p70S6K and phosphorylated tau (p-tau) in cellular models and Alzheimer's disease brains.
- To determine if p70S6K activation influences tau translation and phosphorylation in neuronal cells.
Main Methods:
- In vitro kinase assays to assess direct tau phosphorylation by p70S6K.
- Immunoprecipitation to examine the association between p-p70S6K and p-tau.
- Cellular studies using SH-SY5Y cells with zinc-induced p70S6K activation and overexpression of wild-type human tau (htau40).
- Analysis of p-p70S6K and p-tau levels in post-mortem Alzheimer's disease brain samples.
Main Results:
- p70S6K directly phosphorylates tau at specific sites (S262, S214, T212) in vitro.
- Activated p70S6K (p-p70S6K at T421/S424) is associated with phosphorylated tau (p-tau at S262 and S396/404).
- p70S6K activation upregulates the translation of total S6 and tau, but not global proteins, in SH-SY5Y cells.
- Levels of p-p70S6K (T421/S424) significantly correlate with specific tau phosphorylation sites (S262, S214, T212) in Alzheimer's disease brains.
Conclusions:
- p70S6K directly phosphorylates tau protein.
- p70S6K activation is associated with tau phosphorylation and may play a role in Alzheimer's disease pathogenesis.
- Targeting p70S6K signaling could be a potential therapeutic strategy for Alzheimer's disease.
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