Tyrosine phosphorylation of the β-amyloid precursor protein cytoplasmic tail promotes interaction with Shc

Philip E. Tarr, Roberta Roncarati, Giuliana Pelicci, Pier Giuseppe Pelicci, Luciano D'Adamio

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

β-Amyloid precursor protein (APP) is a widely expressed transmembrane protein of unknown function that is involved in the pathogenesis of Alzheimer's disease. The cytoplasmic tail of APP interacts with phosphotyrosine binding (PTB) domain containing proteins (Fe65, X11, mDab-1, and JIP-1) and may modulate gene expression and apoptosis. We now identify Shc A and Shc C, PTB-containing adapter proteins that signal to cellular differentiation and survival pathways, as novel APP-interacting proteins. The APP cytoplasmic tail contains a PTB-binding motif (Y682ENPTY687) that, when phosphorylated on Tyr682, precipitated the PTB domain of Shc A and Shc C, as well as endogenous full-length Shc A. APP and Shc C were physically associated in adult mouse brain homogenates. Increase in phosphorylation of APP by overexpression of the nerve growth factor receptor Trk A in 293T cells promoted the interaction of transfected APP and endogenous Shc A. Pervanadate treatment of N2a neuroblastoma cells resulted in tyrosine phosphorylation and association of endogenous APP and Shc A. Thus, APP and Shc proteins interact in vitro, in cells, and in the mouse brain. Tyrosine phosphorylation of APP may promote the interaction with Shc proteins.

Original languageEnglish (US)
Pages (from-to)16798-16804
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number19
DOIs
StatePublished - May 10 2002

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Phosphorylation
Amyloid beta-Protein Precursor
Tyrosine
Tail
Phosphotyrosine
Serum Amyloid A Protein
Proteins
Brain
Nerve Growth Factor Receptor
HEK293 Cells
Protein C
Neuroblastoma
Cell Communication
Gene expression
Alzheimer Disease
Apoptosis
Gene Expression
Association reactions

ASJC Scopus subject areas

  • Biochemistry

Cite this

Tyrosine phosphorylation of the β-amyloid precursor protein cytoplasmic tail promotes interaction with Shc. / Tarr, Philip E.; Roncarati, Roberta; Pelicci, Giuliana; Pelicci, Pier Giuseppe; D'Adamio, Luciano.

In: Journal of Biological Chemistry, Vol. 277, No. 19, 10.05.2002, p. 16798-16804.

Research output: Contribution to journalArticle

Tarr, Philip E. ; Roncarati, Roberta ; Pelicci, Giuliana ; Pelicci, Pier Giuseppe ; D'Adamio, Luciano. / Tyrosine phosphorylation of the β-amyloid precursor protein cytoplasmic tail promotes interaction with Shc. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 19. pp. 16798-16804.
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