Synergistic control mechanism for abnormal site phosphorylation of Alzheimer's diseased brain tau by kinase F(A)/GSK-3α

S. D. Yang, J. S. Yu, W. K. Liu, S. H. Yen

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

When a synthetic peptide fragment (VAVVRTPPKSPSSAK) which corresponds to amino acid residues 226-240 from brain microtubule-associated protein tau was used as a testing substrate, we found that protein kinase F(A)/GSK-3α was almost inactive towards this substrate. In sharp contrast, when Ser-10 of this peptide was replaced by a phosphoserine, the phosphopeptide fragment (VAVVRTPPKS((P))PSSAK) became an excellent substrate for kinase F(A)/GSK- 3α. Sequential manual Edman degradation together with phosphoamino acid analysis and protein sequencing further revealed that Thr-6 of the peptide fragment which corresponds to an important abnormal phosphorylation site Thr- 231 in Alzheimer's diseased brain tau was the only site that was greatly phosphorylated, demonstrating that a pre-phosphorylation becomes a prerequisite and is essential for promoting phosphorylation of Thr-231. Taken together, the results provide initial evidence that kinase F(A)/GSK-3α mediates a synergistic phosphorylation control mechanism involved in the abnormal site phosphorylation of Alzheimer's diseased brain tau.

Original languageEnglish (US)
Pages (from-to)400-406
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume197
Issue number2
DOIs
StatePublished - 1993
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this