Dab 1 binds to Fe65 and diminishes the effect of Fe65 or LRP1 on APP processing

Title
Dab 1 binds to Fe65 and diminishes the effect of Fe65 or LRP1 on APP processing
Authors
권오연황경희김점아김광명권익찬송현규전혜성
Keywords
Dab 1; Fe65; PHOSPHOTYROSINE-BINDING DOMAIN; NPTY MOTIF; APP PROCESSING; LRP
Issue Date
2010-10
Publisher
Journal of cellular biochemistry
Citation
VOL 111, NO 2, 508-519
Abstract
Fe65 and Dab1 are adaptor proteins that interact with the cytoplasmic domain of amyloid precursor protein (APP) via phosphotyrosinebinding (PTB) domain and that affect APP processing and Ab production. Co-expression of Dab1 with Fe65 and APP resumed nuclear translocation of Fe65 despite of its cytoplasmic anchor, APP. The decreased amount of Fe65 bound to APP was shown in co-immunoprecipitation assay from the cells with Dab1 which also displayed the effect on APP processing. These data suggested that Fe65 and Dab1 compete for binding to APP. Surprisingly, we found that Fe65 interacts with Dab1 via C-terminal region of Dab1 and unphosphorylated Dab1 is capable of binding Fe65. Dab1 interacts with the low-density lipoprotein receptor-related protein (LRP) as well as APP through its PTB domain. Dab1 significantly decreased the amount of APP bound to LRP and the level of secreted APP and APP-CTF in LRP expressing cells, unlike Fe65. It implies that overexpression of Dab1 diminish LRP–APP complex formation, resulting in altered APP processing. The competition for overlapped binding site among adaptor proteins may be related to the regulation mechanism of APP metabolism in various conditions.
URI
http://pubs.kist.re.kr/handle/201004/40619
ISSN
0730-2312
Appears in Collections:
KIST Publication > Article
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