PHOSPHORYLATION OF TAU BY CYCLIC-AMP-DEPENDENT PROTEIN-KINASE

被引：34

作者：

ROBERTSON, J

LOVINY, TLF

GOEDERT, M

JAKES, R

MURRAY, KJ

ANDERTON, BH

HANGER, DP

机构：

[1] INST PSYCHIAT,DEPT NEUROSCI,DE CRESPIGNY PK,DENMARK HILL,LONDON SE5 8AF,ENGLAND

[2] MRC,MOLEC BIOL LAB,CAMBRIDGE,ENGLAND

[3] SMITHKLINE BEECHAM,WELWYN GARDEN CIT,ENGLAND

来源：

DEMENTIA | 1993年 / 4卷 / 05期

基金：

英国惠康基金;

关键词：

PROTEIN PHOSPHORYLATION; ALZHEIMER DISEASE; MICROTUBULE-ASSOCIATED PROTEINS; TAU; CYCLIC-AMP-DEPENDENT PROTEIN KINASE;

D O I：

10.1159/000107331

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Alzheimer's disease paired helical filaments contain abnormally phosphorylated tau (PHF-tau) which has reduced electrophoretic mobility on sodium dodecyl sulphate polyacrylamide electrophoresis. We have investigated the effects of cyclic-AMP-dependent protein kinase (PKA) on recombinant human tau isoforms and two recombinant tau fragments. PKA phosphorylated tau and reduced its electrophoretic mobility, phosphorylation towards the C-terminus of tau having a major influence on this property. Substitution of serine396 (phosphorylated in PHF-tau) or serine416 (phosphorylated by calcium/calmodulin kinase II) by alanine demonstrated that these are not major sites for PKA phosphorylation. Although the phosphorylated forms of tau generated by PKA are not identical to those of PHF-tau, PKA may be involved in the generation of PHF-tau in Alzheimer's disease via phosphorylation of additional, as yet unidentified, sites on tau.

引用

页码：256 / 263

页数：8

共 33 条

[1] THE SWITCH OF TAU-PROTEIN TO AN ALZHEIMER-LIKE STATE INCLUDES THE PHOSPHORYLATION OF 2 SERINE PROLINE MOTIFS UPSTREAM OF THE MICROTUBULE BINDING REGION [J].