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 |
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Authors: | Bressler SL; Gray MD; Sopher BL; Hu Q; Hearn MG; Pham DG; Dinulos MB; Fukuchi K; Sisodia SS; Miller MA; Disteche CM; Martin GM |
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Institution: | Department of Pathology, University of Washington School of Medicine, Seattle 98195-7470, USA. |
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Abstract: | Using the yeast two hybrid system, a mouse embryo cDNA library was screened
for proteins that interact with the C-terminus of the human beta-amyloid
precursor protein (beta PP). A fusion protein was identified that interacts
specifically with the cytoplasmic domain of beta PP and does not interact
with the beta-amyloid region. The protein encoded by this partial mouse
cDNA is identical to the C-terminus of the rat Fe65 protein. This mouse
protein also interacts with the homologous C-terminal domains of the mouse
amyloid precursor-like proteins, APLP1 and APLP2. These conserved
cytoplasmic regions contain a common amino acid motif, Asn-Pro-Thr-Tyr,
which has previously been shown to influence both the secretion and
internalization of beta PP. Fe65 has been implicated in regulatory and cell
signaling mechanisms because it contains two different motifs involved in
protein binding, a WW domain (a variant of Src homology 3 domains) and a
phosphotyrosine interaction domain (PID). Interestingly, the PID domain
binds to the same motif present in the conserved cytoplasmic domains of the
beta PP and beta PP-like proteins. RNA analyses reveal that Fe65 is
predominantly expressed in brain and in the regions most affected by
Alzheimer's disease (AD)-associated neuropathology. The human Fe65 mRNA was
cloned from a fetal brain cDNA library. The message encodes a protein of
735 amino acids that is 95% identical to the rat Fe65 protein. The human
Fe65 gene was mapped on human metaphase chromosomes to band 11p15 using
fluorescence in situ hybridization.
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