Evidence for a role of the nerve growth factor receptor TrkA in tyrosine phosphorylation and processing of β-APP

Philip E. Tarr, Cristina Contursi, Roberta Roncarati, Cristiana Noviello, Enrico Ghersi, Meir H. Scheinfeld, Nicola Zambrano, Tommaso Russo, Luciano D'Adamio

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

The cytoplasmic tail of the β-amyloid precursor protein (APP) contains a Y682 ENPTY687 sequence through which APP associates with phosphotyrosine binding (PTB) domain containing proteins in a tyrosine phosphorylation-independent manner. We have recently found that tyrosine phosphorylation of APP-Y682 promotes docking of Shc proteins that modulate growth factor signaling to the ERK and PI3K/Akt pathways. We have also shown that APP is phosphorylated on Y682 in cells that overexpress a constitutively active form of the tyrosine kinase abl. Here we present evidence that the nerve growth factor receptor TrkA may also promote phosphorylation of APP. Overexpression of TrkA, but not of mutated, kinase inactive TrkA resulted in tyrosine phosphorylation of APP. Site-directed mutagenesis studies showed that TrkA overexpression was associated with phosphorylation of APP-Y682. Moreover, overexpression of TrkA also affected APP processing reducing the generation of the APP intracellular domain (AID). Thus, tyrosine phosphorylation of APP may functionally link APP processing and neurotrophic signaling to intracellular pathways associated with cellular differentiation and survival.

Original languageEnglish (US)
Pages (from-to)324-329
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume295
Issue number2
DOIs
StatePublished - 2002

Fingerprint

Nerve Growth Factor Receptor
Phosphorylation
Amyloid beta-Protein Precursor
Tyrosine
Processing
Phosphotyrosine
Mutagenesis
Site-Directed Mutagenesis
Phosphatidylinositol 3-Kinases
Amyloid
Protein-Tyrosine Kinases
Intercellular Signaling Peptides and Proteins
Phosphotransferases
Proteins

Keywords

  • AID
  • APP
  • Shc
  • TrkA
  • Tyrosine phosphorylation
  • YENPTY

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Evidence for a role of the nerve growth factor receptor TrkA in tyrosine phosphorylation and processing of β-APP. / Tarr, Philip E.; Contursi, Cristina; Roncarati, Roberta; Noviello, Cristiana; Ghersi, Enrico; Scheinfeld, Meir H.; Zambrano, Nicola; Russo, Tommaso; D'Adamio, Luciano.

In: Biochemical and Biophysical Research Communications, Vol. 295, No. 2, 2002, p. 324-329.

Research output: Contribution to journalArticle

Tarr, Philip E. ; Contursi, Cristina ; Roncarati, Roberta ; Noviello, Cristiana ; Ghersi, Enrico ; Scheinfeld, Meir H. ; Zambrano, Nicola ; Russo, Tommaso ; D'Adamio, Luciano. / Evidence for a role of the nerve growth factor receptor TrkA in tyrosine phosphorylation and processing of β-APP. In: Biochemical and Biophysical Research Communications. 2002 ; Vol. 295, No. 2. pp. 324-329.
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