Phosphorylation of microtubule‐associated protein tau by stress‐activated protein kinases in intact cells

FEBS Letters

Buée-Scherrer, Valérie¹  Goedert, Michel¹ 

[1] Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK

关键词: Abnormal hyperphosphorylation;    Stress-activated protein kinase;    Tau protein;    Tauopathy;   

DOI  :  10.1016/S0014-5793(02)02460-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Tau is a microtubule-associated protein that is abnormally hyperphosphorylated in the filamentous lesions that define a number of neurodegenerative diseases collectively referred to as tauopathies. We previously showed that stress-activated protein (SAP) kinases phosphorylate tau protein at many of the hyperphosphorylated sites in vitro. Here we have developed a system to study the effects of five SAP kinases (SAPK1c/JNK1, SAPK2a/p38α, SAPK2b/p38β, SAPK3/p38γ and SAPK4/p38δ) on tau phosphorylation in intact cells. All kinases phosphorylated tau, albeit at different efficiencies. Tau was a good substrate for SAPK3/p38γ and SAPK4/p38δ, a reasonable substrate for SAPK2b/p38β and a relatively poor substrate for SAPK2a/p38α and SAPK1c/JNK1. These findings indicate that the aberrant activation of SAP kinases, especially SAPK3/p38γ and SAPK4/p38δ, could play an important role in the abnormal hyperphosphorylation of tau that is an invariant feature of the tauopathies.

【 授权许可】

Unknown