Interaction of the phosphotyrosine interaction/phosphotyrosine binding-related domains of Fe65 with wild-type and mutant Alzheimer's beta-amyloid precursor proteins.
The two tandem phosphotyrosine interaction/phosphotyrosine binding (PID/PTB) domains of the Fe65 protein interact with the intracellular region of the Alzheimer's beta-amyloid precursor protein (APP). This interaction, previously demonstrated in vitro and in the yeast two hybrid system, also takes place in vivo in mammalian cells, as demonstrated here by anti-Fe65 co-immunoprecipitation experiments. This interaction differs from that occurring between other PID/PTB domain-containing proteins, such as Shc and insulin receptor substrate 1, and activated growth factor receptors as follows: (i) the Fe65-APP interaction is phosphorylation-independent; (ii) the region of the APP intracellular domain involved in the binding is larger than that of the growth factor receptor necessary for the formation of the complex with Shc; and (iii) despite a significant similarity the carboxyl-terminal regions of PID/PTB of Fe65 and of Shc are not functionally interchangeable in terms of binding cognate ligands. A role for Fe65 in the pathogenesis of familial Alzheimer's disease is suggested by the finding that mutant APP, responsible for some cases of familial Alzheimer's disease, shows an altered in vivo interaction with Fe65.
Zambrano
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Dipartimento di Biochimica e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, CEINGE Biotecnologie Avanzate s.c. r.l., via S. Pansini 5, 80131 Naples, Italy.
Buxbaum
J D
JD
Minopoli
G
G
Fiore
F
F
De Candia
P
P
De Renzis
S
S
Faraonio
R
R
Sabo
S
S
Cheetham
J
J
Sudol
M
M
Russo
T
T
D000544:Alzheimer Disease / Q000235:genetics*; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D016716:PC12 Cells; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*; D017354:Point Mutation; D011233:Precipitin Tests; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
C091042:APBB1 protein, human; D016564:Amyloid beta-Protein Precursor; C486242:Apbb1 protein, rat; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011506:Proteins; D019000:Phosphotyrosine