Abstract
Several kinases have been shown to phosphorylate tau protein at Ser-262, an important site involved in the regulation of the binding of tau to microtubules. In this study we compared the phosphorylation of tau at Ser-262 by CaMKII, PhK and PKA in vitro as determined by radioimmunoblots developed by the monoclonal antibody 12E8 which recognizes P-Ser-262 and P-Ser-356; and Ab-262, a polyclonal antibody which is specific to unphosphorylated Ser-262 in tau. We found that the phosphorylation at Ser-262 was several times more effective by CaMKII than PKA or PhK. Employing rat brain extract as a source of all brain kinases and KN-62, a specific inhibitor of CaMKII, we found that CaMKII accounts for ~45% of phosphorylation at Ser-262. Furthermore, in rat brain slices kept metabolically active in oxygenated artificial CSF, phosphorylation of tau at Ser-262 was (i) increased up to 120% in the presence of bradykinin, a CaMKII activator, and (ii) inhibited by ~35% in the presence of KN-62. Thus, CaMKII is a major tau Ser-262 kinase in mammalian brain. Copyright (C) 1998 Federation of European Biochemical Societies.
Original language | English (US) |
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Pages (from-to) | 471-475 |
Number of pages | 5 |
Journal | FEBS Letters |
Volume | 436 |
Issue number | 3 |
DOIs | |
State | Published - Oct 9 1998 |
Keywords
- Alzheimer's disease
- Calcium calmodulin kinase II
- Phosphorylase kinase
- Protein kinase A
- Ser-262
- Tau phosphorylation
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology