Phosphorylation of a tyrosine in the amyloid-β protein precursor intracellular domain inhibits Fe65 binding and signaling

Dawang Zhou, Nicola Zambrano, Tommaso Russo, Luciano D'Adamio

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The phosphorylation of Tyr-682 residue in the intracellular domain (AID) of amyloid-β protein precursor (AβPP) is significantly enhanced in Alzheimer's disease patients' brain. The role of this phosphotyrosine, however, remains elusive. Here we report that phosphorylation of Tyr-682 inhibits the interactions between AβPP and Fe65, which is the main regulatory mechanism controlling Fe65 nuclear signaling. Furthermore, we show that tyrosine phosphorylation of AβPP also inhibits interaction of the two other Fe65 family members, Fe65L1 and Fe65L2. Likewise, docking of Fe65, Fe65L1 and Fe65L2 to APLP1 and APLP2, the two other members of the AβPP-gene family, is abolished by analogous phosphorylation events. Our results indicate that phosphorylation of the cytoplasmic tail of AβPP on Tyr-682 represents a second mechanism, alternative to AβPP processing by secretases, that regulates AβPP/Fe65 downstream signaling pathways.

Original languageEnglish (US)
Pages (from-to)301-307
Number of pages7
JournalJournal of Alzheimer's Disease
Volume16
Issue number2
DOIs
StatePublished - 2009

Fingerprint

Amyloid beta-Protein Precursor
Tyrosine
Phosphorylation
Amyloid Precursor Protein Secretases
Phosphotyrosine
Alzheimer Disease
Brain
Genes

Keywords

  • Amyloid-β protein precursor
  • Fe65
  • Phosphorylation
  • Threonine
  • Tyrosine

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

Cite this

Phosphorylation of a tyrosine in the amyloid-β protein precursor intracellular domain inhibits Fe65 binding and signaling. / Zhou, Dawang; Zambrano, Nicola; Russo, Tommaso; D'Adamio, Luciano.

In: Journal of Alzheimer's Disease, Vol. 16, No. 2, 2009, p. 301-307.

Research output: Contribution to journalArticle

Zhou, Dawang ; Zambrano, Nicola ; Russo, Tommaso ; D'Adamio, Luciano. / Phosphorylation of a tyrosine in the amyloid-β protein precursor intracellular domain inhibits Fe65 binding and signaling. In: Journal of Alzheimer's Disease. 2009 ; Vol. 16, No. 2. pp. 301-307.
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