Kwon, Oh Yeun Hwang, Kyounghee Kim, Jeom-A Kim, Kwangmyung Kwon, Ick Chan Song, Hyun Kyu Jeon, Hyesung 2024-01-20T18:31:25Z 2024-01-20T18:31:25Z 2021-09-05 2010-10-01 0730-2312 https://pubs.kist.re.kr/handle/201004/131015 Fe65 and Dab1 are adaptor proteins that interact with the cytoplasmic domain of amyloid precursor protein (APP) via phosphotyrosine-binding (PTB) domain and that affect APP processing and A beta 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. J. Cell. Biochem. 111: 508-519, 2010. (C) 2010 Wiley-Liss, Inc. English WILEY AMYLOID PRECURSOR PROTEIN RECEPTOR-RELATED PROTEIN ALZHEIMERS-DISEASE ADAPTER PROTEIN BRAIN-DEVELOPMENT APOE RECEPTOR DISABLED 1 INTRACELLULAR DOMAIN CYTOPLASMIC DOMAIN CYTOSOLIC ADAPTER Dab1 Binds to Fe65 and Diminishes the Effect of Fe65 or LRP1 on APP Processing Article 10.1002/jcb.22738 1 JOURNAL OF CELLULAR BIOCHEMISTRY, v.111, no.2, pp.508 - 519 JOURNAL OF CELLULAR BIOCHEMISTRY 111 2 508 519 scie scopus 000282482400027 2-s2.0-77957274433 Biochemistry & Molecular Biology Cell Biology Biochemistry & Molecular Biology Cell Biology Article AMYLOID PRECURSOR PROTEIN RECEPTOR-RELATED PROTEIN ALZHEIMERS-DISEASE ADAPTER PROTEIN BRAIN-DEVELOPMENT APOE RECEPTOR DISABLED 1 INTRACELLULAR DOMAIN CYTOPLASMIC DOMAIN CYTOSOLIC ADAPTER Dab1 Fe65 PHOSPHOTYROSINE-BINDING DOMAIN NPTY MOTIF APP PROCESSING LRP