Ser-262 in human recombinant tau protein is a markedly more favorable site for phosphorylation by CaMKII than PKA or PhK

Juan J. Sironi, Shu Hui Yen, Javed A. Gondal, Qiongli Wu, Inge Grundke-Iqbal, Khalid Iqbal

Research output: Contribution to journalArticle

63 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)471-475
Number of pages5
JournalFEBS Letters
Volume436
Issue number3
DOIs
StatePublished - Oct 9 1998
Externally publishedYes

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Calcium-Calmodulin-Dependent Protein Kinase Type 2
tau Proteins
Recombinant proteins
Phosphorylation
Recombinant Proteins
KN 62
Brain
Phosphotransferases
Rats
Bradykinin
Microtubules
human MAPT protein
Monoclonal Antibodies
Antibodies

Keywords

  • Alzheimer's disease
  • Calcium calmodulin kinase II
  • Phosphorylase kinase
  • Protein kinase A
  • Ser-262
  • Tau phosphorylation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Ser-262 in human recombinant tau protein is a markedly more favorable site for phosphorylation by CaMKII than PKA or PhK. / Sironi, Juan J.; Yen, Shu Hui; Gondal, Javed A.; Wu, Qiongli; Grundke-Iqbal, Inge; Iqbal, Khalid.

In: FEBS Letters, Vol. 436, No. 3, 09.10.1998, p. 471-475.

Research output: Contribution to journalArticle

Sironi, Juan J. ; Yen, Shu Hui ; Gondal, Javed A. ; Wu, Qiongli ; Grundke-Iqbal, Inge ; Iqbal, Khalid. / Ser-262 in human recombinant tau protein is a markedly more favorable site for phosphorylation by CaMKII than PKA or PhK. In: FEBS Letters. 1998 ; Vol. 436, No. 3. pp. 471-475.
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