The neuronal adaptor protein Fe65 is phosphorylated by mitogen-activated protein kinase (ERK1/2)

被引：22

作者：

Standen, CL

Perkinton, MS

Byers, HL

Kesavapany, S

Lau, KF

Ward, M

McLoughlin, D

Miller, CCJ

机构：

[1] Kings Coll London, Inst Psychiat, Dept Neurosci, London SE5 8AF, England

[2] Kings Coll London, Inst Psychiat, Dept Neurol, London SE5 8AF, England

[3] Kings Coll London, Inst Psychiat, Dept Old Age Psychiat, London SE5 8AF, England

[4] Kings Coll London, Inst Psychiat, Proteome Sci Plc, London WC2R 2LS, England

来源：

MOLECULAR AND CELLULAR NEUROSCIENCE | 2003年 / 24卷 / 04期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1016/j.mcn.2003.07.002

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Fe65 is a neuronal adaptor protein that binds a number of ligands and which functions in both gene transcription/nuclear signalling and in the regulation of cell migration and motility. These different functions within the nucleus and at the cell surface are mediated via Fe65's different binding partners. An Fe65/APP/TIP60 complex is transcriptionally active within the nucleus and an Fe65/APP/Mena complex probably regulates actin dynamics in lamellipodia. The mechanisms that regulate these different Fe65 functions are unclear. Here, we demonstrate that Fe65 is a phosphoprotein and, using mass spectrometry sequencing, identify for the first time in vivo phosphorylation sites in Fe65. We also show that Fe65 is a substrate for phosphorylation by the mitogen-activated protein kinases ERK1/2. Our results provide a mechanism by which Fe65 function may be modulated to fulfil its various roles. (C) 2003 Elsevier Inc. All rights reserved.

引用

收藏

页码：851 / 857

页数：7

相关论文

共 37 条

[1] Phosphorylation-dependent regulation of the interaction of amyloid precursor protein with Fe65 affects the production of β-amyloid [J].

Ando, K ;

Iijima, K ;

Elliott, JI ;

Kirino, Y ;

Suzuki, T .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (43) :40353-40361

[2] Exchange of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-κB and β-amyloid precursor protein [J].

Baek, SH ;

Ohgi, KA ;

Rose, DW ;

Koo, EH ;

Glass, CK ;

Rosenfeld, MG .

CELL, 2002, 110 (01) :55-67

[3] The dual role of cytoskeletal anchor proteins in cell adhesion and signal transduction [J].

Ben-Ze'Ev, A .

ANTICANCER MOLECULES: STRUCTURE, FUNCTION, AND DESIGN, 1999, 886 :37-47

[4] Identification of phosphorylation sites on neurofilament proteins by nanoelectrospray mass spectrometry [J].

Betts, JC ;

Blackstock, WP ;

Ward, MA ;

Anderton, BH .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (20) :12922-12927

[5] Mapping of the human and murine X11-like genes (APBA2 and Apba2), the murine Fe65 gene (Apbb1), and the human Fe65-like gene (APBB2):: genes encoding phosphotyrosine-binding domain proteins that interact with the Alzheimer's disease amyloid precursor protein [J].

Blanco, G ;

Irving, NG ;

Brown, SDM ;

Miller, CCJ ;

McLoughlin, DM .

MAMMALIAN GENOME, 1998, 9 (06) :473-475

[6]

Borg JP, 1996, MOL CELL BIOL, V16, P6229

[7] cDNA cloning and chromosome mapping of the human Fe65 gene: Interaction of the conserved cytoplasmic domains of the human beta-amyloid precursor protein and its homologues with the mouse Fe65 protein [J].

Bressler, SL ;

Gray, MD ;

Sopher, BL ;

Hu, QB ;

Hearn, MG ;

Pham, DG ;

Dinulos, MB ;

Fukuchi, KI ;

Sisodia, SS ;

Miller, MA ;

Disteche, CM ;

Martin, GM .

HUMAN MOLECULAR GENETICS, 1996, 5 (10) :1589-1598

[8] A transcriptively active complex of APP with Fe65 and histone acetyltransferase Tip60 [J].

Cao, XW ;

Südhof, TC .

SCIENCE, 2001, 293 (5527) :115-120

[9] A risk for early-onset Alzheimer's disease associated with the APBB1 gene (FE65) intron 13 polymorphism [J].

Cousin, E ;

Hannequin, D ;

Ricard, S ;

Macé, S ;

Génin, E ;

Chansac, C ;

Brice, A ;

Dubois, B ;

Frebourg, T ;

Mercken, L ;

Benavides, J ;

Pradier, L ;

Campion, D ;

Deleuze, JF .

NEUROSCIENCE LETTERS, 2003, 342 (1-2) :5-8

[10] The amyloid precursor protein (APP)-cytoplasmic fragment generated by γ-secretase is rapidly degraded but distributes partially in a nuclear fraction of neurones in culture [J].

Cupers, P ;

Orlans, I ;

Craessaerts, K ;

Annaert, W ;

De Strooper, B .

JOURNAL OF NEUROCHEMISTRY, 2001, 78 (05) :1168-1178

← 1 2 3 4 →