Akt/PKB kinase phosphorylates separately Thr212 and Ser214 of tau protein in vitro

Hanna Ksiezak-Reding, Han Kyoung Pyo, Boris Feinstein, Giulio M. Pasinetti

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

Microtubule-associated protein tau contains a consensus motif for protein kinase B/Akt (Akt), which plays an essential role in anti-apoptotic signaling. The motif encompasses the AT100 double phospho-epitope (Thr212/Ser214), a specific marker for Alzheimer's disease (AD) and other neurodegenerations, raising the possibility that it could be generated by Akt. We studied Akt-dependent phosphorylation of tau protein in vitro. We found that Akt phosphorylated both Thr212 and Ser214 in the longest and shortest tau isoforms as determined using phospho site-specific antibodies against tau. Akt did not phosphorylate other tau epitopes, including Tau-1, AT8, AT180, 12E8 and PHF-1. The Akt-phosphorylated tau retained its initial electrophoretic mobility. Immunoprecipitation studies with phospho-specific Thr212 and Ser214 antibodies revealed that only one of the two sites is phosphorylated per single tau molecule, resulting in tau immunonegative for AT100. Mixed kinase studies showed that prior Ser214 phosphorylation by Akt blocked protein kinase A but not GSK3β activity. On the other hand, GSK3β selectively blocked Ser214 phosphorylation, which was prevented by lithium. The results suggest that Akt may be involved in AD-specific phosphorylation of tau at the AT100 epitope in conjunction with other kinases. Our data suggest that phosphorylation of tau by Akt may play specific role(s) in Akt-mediated anti-apoptotic signaling, particularly relevant to AD and other neurodegenerations.

Original languageEnglish
Pages (from-to)159-168
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1639
Issue number3
DOIs
StatePublished - 20 Nov 2003

Keywords

  • AT100 epitope
  • Akt/protein kinase B
  • Alzheimer's disease
  • Glycogen synthase kinase 3β
  • Protein kinase A
  • Tau

Fingerprint

Dive into the research topics of 'Akt/PKB kinase phosphorylates separately Thr212 and Ser214 of tau protein in vitro'. Together they form a unique fingerprint.

Cite this