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Phosphorylation of microtubule‐associated protein tau by stress‐activated protein kinases in intact cells
Author(s) -
Buée-Scherrer Valérie,
Goedert Michel
Publication year - 2002
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/s0014-5793(02)02460-2
Subject(s) - p38 mitogen activated protein kinases , kinase , phosphorylation , tau protein , hyperphosphorylation , microbiology and biotechnology , microtubule , mitogen activated protein kinase , protein kinase a , chemistry , biology , medicine , alzheimer's disease , pathology , disease
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.