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

Details

Serval ID
serval:BIB_4BB28CDF8D1E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Evidence for a role of the nerve growth factor receptor TrkA in tyrosine phosphorylation and processing of beta-APP
Journal
Biochemical and Biophysical Research Communications
Author(s)
Tarr  P. E., Contursi  C., Roncarati  R., Noviello  C., Ghersi  E., Scheinfeld  M. H., Zambrano  N., Russo  T., D'Adamio  L.
ISSN
0006-291X
Publication state
Published
Issued date
07/2002
Peer-reviewed
Oui
Volume
295
Number
2
Pages
324-9
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Jul 12
Abstract
The cytoplasmic tail of the beta-amyloid precursor protein (APP) contains a Y(682)ENPTY(687) 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-Y(682) 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 Y(682) 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-Y(682). 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.
Keywords
Amyloid beta-Protein Precursor/*metabolism Cell Line Cytoplasm/metabolism Humans Mutagenesis, Site-Directed Phosphorylation *Protein Processing, Post-Translational Receptor, trkA/chemistry/*physiology
Pubmed
Web of science
Create date
20/01/2008 16:55
Last modification date
20/08/2019 13:59
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