The c-Abl tyrosine kinase phosphorylates the Fe65 adaptor protein to stimulate Fe65/amyloid precursor protein nuclear signaling.
Citation:
Perkinton, MS, Standen, CL, Lau, KF, Kesavapany, S, Byers, HL, Ward, M, McLoughlin, DM, Miller, CC, `The c-Abl tyrosine kinase phosphorylates the Fe65 adaptor protein to stimulate Fe65/amyloid precursor protein nuclear signaling? in The Journal of Biological Chemistry, 279, (21), 2004, pp 22084 - 22091Download Item:
Abstract:
The amyloid precursor protein (APP) is proteolytically
processed to release a C-terminal domain that signals
to the nucleus to regulate transcription of responsive
genes. The APP C terminus binds to a number of
phosphotyrosine binding (PTB) domain proteins and
one of these, Fe65, stimulates APP nuclear signaling.
Fe65 is an adaptor protein that contains a number of
protein-protein interaction domains. These include two
PTB domains, the second of which binds APP, and a WW
domain that binds proline-rich ligands. One ligand for
the Fe65WW domain is the tyrosine kinase c-Abl. Here,
we show that active c-Abl stimulates APP/Fe65-mediated
gene transcription and that this effect is mediated
by phosphorylation of Fe65 on tyrosine 547 within its
second PTB domain. The homologous tyrosine within
the motif Tyr-(Leu/Met)-Gly is conserved in a variety of
PTB domains, and this suggests that PTB tyrosine phosphorylation
occurs in other proteins. As such, PTB domain
phosphorylation may represent a novel mechanism
for regulating the function of this class of protein.
Sponsor
Grant Number
Wellcome Trust
European Union (EU)
Author's Homepage:
http://people.tcd.ie/mclougdeDescription:
PUBLISHED
Author: MCLOUGHLIN, DECLAN
Publisher:
American Society for Biochemistry and Molecular BiologyType of material:
Journal ArticleCollections
Series/Report no:
The Journal of Biological Chemistry279
21
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PsychiatryMetadata
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