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Rapid Alzheimer‐like phosphorylation of tau by the synergistic actions of non‐proline‐dependent protein kinases and GSK‐3
Author(s) -
Singh Toolsee J.,
Haque Niloufar,
Grundke-Iqbal Inge,
Iqbal Khalid
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(94)01445-7
Subject(s) - phosphorylation , kinase , tau protein , hyperphosphorylation , gsk 3 , gene isoform , chemistry , protein kinase a , biochemistry , microbiology and biotechnology , alzheimer's disease , biology , medicine , gene , disease
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.