The intracellular cytoplasmic domain of the Alzheimer's disease amyloid precursor protein interacts with phosphotyrosine-binding domain proteins in the yeast two-hybrid system.

We have used the yeast two-hybrid system to screen for proteins that interact with the carboxy-terminal domain of APP. Six different clones were isolated and sequence analyses revealed that they encoded domains of a previously described neuronal protein Fe65, a homologue of Fe65 and a homologue of protein X11. All of these proteins contain one or more phosphotyrosine binding (PTB) domains. PTB domain proteins bind to the sequence Asn-Pro-X-Tyr when the Tyr is phosphorylated and are believed to function in signal transduction. APP contains such a motif. These results are consistent with a role for APP in signal transduction mechanisms.