Synergistic control mechanism for abnormal site phosphorylation of Alzheimer′s diseased brain tau by kinase FA/GSK-3α

Shiaw Der Yang, Jau Song Yu, Wan Kyng Liu, Shu Hui Yen

Research output: Contribution to journalArticlepeer-review

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 FA/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)PS S A K) became an excellent substrate for kinase FA/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 FA/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 - Dec 15 1993

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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