Growth factor receptor-bound protein 2 interaction with the tyrosine-phosphorylated tail of amyloid β precursor protein is mediated by its Src homology 2 domain

Dawang Zhou, Cristiana Noviello, Chiara D'Ambrosio, Andrea Scaloni, Luciano D'Adamio

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

The sequential processing of the familial disease gene product amyloid β precursor protein (AβPP) by β- and γ-secretases generates amyloid β, which is considered to be the pathogenic factor of Alzheimer's disease, and the AID peptide (AβPP intracellular domain). The AID peptide acts as a positive regulator of apoptosis and modulates transcription and calcium release. To gain clues about the molecular mechanisms regulating the function of AβPP and AID, proteins interacting with the AID region of AβPP have been isolated using the yeast two-hybrid system. Recent evidence indicates that AβPP undergoes post-translational modification events in the AID region and that phosphorylation might regulate its affinity for interacting proteins. To test this possibility and to uncover AβPP-binding partners whose interaction depends on AβPP phosphorylation, we used a proteomic approach. Here we describe a protein, growth factor receptor-bound protein 2 (Grb2), that specifically binds AβPP, phosphorylated in Tyr682. Furthermore, we show that this interaction is direct and that Grb2 binds to phospho-AβPP via its Src homology 2 region. Together with the evidence that Grb2 is in complex with AβPP in human brains and that these complexes are augmented in brains from Alzheimer's cases, our data indicate that Grb2 may mediate some biological and possibly pathological AβPP-AID function.

Original languageEnglish (US)
Pages (from-to)25374-25380
Number of pages7
JournalJournal of Biological Chemistry
Volume279
Issue number24
DOIs
StatePublished - Jun 11 2004

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GRB2 Adaptor Protein
src Homology Domains
Amyloid beta-Protein Precursor
Tyrosine
Tail
Amyloid
Phosphorylation
Brain
Amyloid Precursor Protein Secretases
Peptides
Two-Hybrid System Techniques
Proteins
Post Translational Protein Processing
Protein Binding
Proteomics
Transcription
Hybrid systems
Yeast
Alzheimer Disease
Apoptosis

ASJC Scopus subject areas

  • Biochemistry

Cite this

Growth factor receptor-bound protein 2 interaction with the tyrosine-phosphorylated tail of amyloid β precursor protein is mediated by its Src homology 2 domain. / Zhou, Dawang; Noviello, Cristiana; D'Ambrosio, Chiara; Scaloni, Andrea; D'Adamio, Luciano.

In: Journal of Biological Chemistry, Vol. 279, No. 24, 11.06.2004, p. 25374-25380.

Research output: Contribution to journalArticle

Zhou, Dawang ; Noviello, Cristiana ; D'Ambrosio, Chiara ; Scaloni, Andrea ; D'Adamio, Luciano. / Growth factor receptor-bound protein 2 interaction with the tyrosine-phosphorylated tail of amyloid β precursor protein is mediated by its Src homology 2 domain. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 24. pp. 25374-25380.
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