Rapid Alzheimer‐like phosphorylation of tau by the synergistic actions of non‐proline‐dependent protein kinases and GSK‐3

FEBS Letters

Singh, Toolsee J.¹  Grundke-Iqbal, Inge¹  Haque, Niloufar¹  Iqbal, Khalid¹ 

[1] New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA

关键词: GSK-3;    Tau protein;    Protein kinase;    Alzheimer's disease;    Paired helical filament;    PHF;    paired helical filament;    A-kinase;    cyclic AMP-dependent protein kinase;    CaM kinase II;    calcium/calmodulin-dependent protein kinase II;    C-kinase;    calcium/phospholipid-dependent protein kinase;    CK-1;    casein kinase-1;    CK-2;    casein kinase-2;    Gr kinase;    calcium/calmodulin-dependent protein kinase from rat cerebellum;    GSK-3;    glycogen synthase kinase-3;    MAP kinase;    mitogen-activated protein kinase;    SDS-PAGE;    sodium dodecyl sulfate-polyacrylamide gel electrophoresis;    PDPK;    proline-dependent protein kinase;   

DOI  :  10.1016/0014-5793(94)01445-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown