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Phosphorylation of microtubule‐associated protein tau by AMPK‐related kinases
Author(s) -
Yoshida Hirotaka,
Goedert Michel
Publication year - 2012
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.1471-4159.2011.07523.x
Subject(s) - phosphorylation , ampk , kinase , microbiology and biotechnology , microtubule , chemistry , protein phosphorylation , protein kinase a , tau protein , microtubule associated protein , protein serine threonine kinases , amp activated protein kinase , biology , medicine , alzheimer's disease , disease
J. Neurochem. (2012) 120 , 165–176. Abstract Microtubule‐associated protein tau is abnormally hyperphosphorylated in the intracellular filamentous inclusions seen in neurodegenerative disorders with dementia, such as Alzheimer’s disease and other tauopathies. Microtubule‐associated protein/microtubule‐affinity regulating kinases (MARKs) have previously been identified as kinases which phosphorylate KxGS motifs in the tandem repeats of tau. They are members of the 5′‐AMP‐activated protein kinase (AMPK)‐related kinases in the Ca 2+ /calmodulin‐dependent protein kinase group. In this study, we examined the ability of AMPK‐related kinases, brain‐specific kinases 1 and 2, maternal embryonic leucine‐zipper kinase, MARK1, and salt‐inducible kinase (SIK), to phosphorylate tau. We found that they phosphorylated S262 and S356 in KxGS motifs in the repeats of tau, thus resulting in immunoreactivity with antibody 12E8. MARK1 and SIK most effectively phosphorylated tau, and their down‐regulation resulted in a reduction of 12E8‐labelling. BX 795, an inhibitor of MARK1 and SIK, reduced 12E8‐immunolabelling of tau in rat cortical neurons. These findings reveal a significant contribution of AMPK‐related kinases to the phosphorylation of tau at S262/S356.