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Phosphorylation of microtubule‐associated protein tau by isoforms of c‐Jun N‐terminal kinase (JNK)
Author(s) -
Yoshida Hirotaka,
Hastie C. James,
McLauchlan Hilary,
Cohen Philip,
Goedert Michel
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02479.x
Subject(s) - phosphorylation , kinase , hyperphosphorylation , threonine , tau protein , serine , microbiology and biotechnology , gene isoform , microtubule , biology , microtubule associated protein , tauopathy , dyrk1a , gsk 3 , chemistry , neurodegeneration , biochemistry , alzheimer's disease , medicine , disease , gene
Abstract Microtubule‐associated protein tau in a hyperphosphorylated state is the major component of the filamentous lesions that define a number of neurodegenerative diseases commonly referred to as tauopathies. Hyperphosphorylation of tau at most sites appears to precede filament assembly. Many of the hyperphosphorylated sites are serine/threonine–proline sequences. Here we show that c‐Jun N‐terminal kinases JNK1, JNK2 and JNK3 phosphorylate tau at many serine/threonine–prolines, as assessed by the generation of the epitopes of phosphorylation‐dependent anti‐tau antibodies. Of the three protein kinases, JNK2 phosphorylated the most sites in tau, followed by JNK3 and JNK1. Phosphorylation by JNK isoforms resulted in a greatly reduced ability of tau to promote microtubule assembly. These findings extend the number of candidate protein kinases for the hyperphosphorylation of tau in Alzheimer's disease and other neurodegenerative disorders.