Rapid Alzheimer‐like phosphorylation of tau by the synergistic actions of non‐proline‐dependent protein kinases and GSK‐3
Open Access
- 30 January 1995
- journal article
- Published by Wiley in FEBS Letters
- Vol. 358 (3) , 267-272
- https://doi.org/10.1016/0014-5793(94)01445-7
Abstract
Tau protein from Alzheimer disease (AD) brain is phosphorylated at eleven Ser/Thr‐Pro and nine Ser/Thr‐X sites. The former sites are phosphorylated by proline‐dependent protein kinases (PDPKs), the latter by non‐PDPKs. The identities of both the PDPKs and non‐PDPKs involved in AD tau hyperphosphorylation are still to be established. In this study we have analyzed the interactions between a PDPK (GSK‐3) and several non‐PDPKs (A‐kinase, C‐kinase, CK‐1, CaM kinase II) in the phosphorylation of one isoform (tau 39) of human tau. We found that the rate of phosphorylation of tau 39 by GSK‐3 was increased several‐fold if tau were first prephosphorylated by the non‐PDPKs. Further, several Alzheimer‐like epitopes in tau can be induced only slowly after phosphorylation of tau by GSK‐3 alone. After a prephosphorylation of tau by the non‐PDPKs, however, the rate of induction of these epitopes by GSK‐3 is increased several‐fold. These results suggest that one role of non‐PDPK‐catalyzed phosphorylation is the modulation of PDPK‐catalyzed phosphorylation of tau in AD brain.Keywords
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