Journal Article

cDNA Cloning and Chromosome Mapping of the Human Fe65 Gene: Interaction of the Conserved Cytoplasmic Domains of the Human β-amyloid Precursor Protein and Its Homologues with the Mouse Fe65 Protein

Steven L. Brassler, Matthew D. Gray, Bryce L. Sopher, Qubai Hu, Mark G. Hearn, Dao G. Pham, Mary Beth Dinulos, Ken-Ichiro Fukuchi, Sangram S. Sisodia, Margaret A. Miller, Christine M. Disteche and George M. Martin

in Human Molecular Genetics

Volume 5, issue 10, pages 1589-1598
Published in print October 1996 | ISSN: 0964-6906
e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/5.10.1589
cDNA Cloning and Chromosome Mapping of the Human Fe65 Gene: Interaction of the Conserved Cytoplasmic Domains of the Human β-amyloid Precursor Protein and Its Homologues with the Mouse Fe65 Protein

Show Summary Details

Preview

Using the yeast two hybrid system, a mouse embryo cDNA library was screened for proteins that interact with the C-terminus of the human β-amyloid precursor protein (βPP). A fusion protein was identified that interacts specifically with the cytoplasmic domain of βPP and does not interact with the β-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 βPP. 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 βPP and βPP-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.

Journal Article.  7860 words.  Illustrated.

Subjects: Genetics and Genomics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.