Phosphorylation of microtubule‐associated protein tau by stress‐activated protein kinases

FEBS Letters

Cuenda, Ana¹  Lawler, Sean¹  Hasegawa, Masato²  Cohen, Philip¹  Goedert, Michel²  Jakes, Ross² 

[1]MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Dundee DD1 4HN, UK

[2]MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK

关键词: Stress-activated protein kinase;    Tau protein;    Microtubule assembly;    Alzheimer's disease;   

DOI  :  10.1016/S0014-5793(97)00483-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The paired helical filament, which comprises the major fibrous element of the neurofibrillary lesions of Alzheimer's disease, is composed of hyperphosphorylated microtubule-associated protein tau. Many of the hyperphosphorylated sites in tau are serine/threonine-prolines. Here we show that the stress-activated protein (SAP) kinases SAPK1γ (also called JNK1), SAPK2a (also called p38, RK, CSBPs, Mpk2 and Mxi2), SAPK2b (also called p38β), SAPK3 (also called ERK6 and p38γ) and SAPK4 phosphorylate tau at many serine/threonine-prolines, as assessed by the generation of the epitopes of phosphorylation-dependent anti-tau antibodies. Based on initial rates of phosphorylation, tau was found to be a good substrate for SAPK4 and SAPK3, a reasonable substrate for SAPK2b and a relatively poor substrate for SAPK2a and SAPK1γ. Phosphorylation of tau by SAPK3 and SAPK4 resulted in a marked reduction in its ability to promote microtubule assembly. These findings double the number of candidate protein kinases for the hyperphosphorylation of tau in Alzheimer's disease and other neurodegenerative disorders.

【 授权许可】

Unknown