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.
McLoughlin
D M
DM
Department of Neurology, The Institute of Psychiatry, De Crespigny Park, Denmark Hill, London, UK.
Miller
C C
CC
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000737:chemistry; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D019151:Peptide Library; D019000:Phosphotyrosine / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D012441:Saccharomyces cerevisiae
C079091:APBA1 protein, human; C091042:APBB1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D016564:Amyloid beta-Protein Precursor; C513072:Apba1 protein, mouse; C513071:Apba1 protein, rat; C486243:Apbb1 protein, mouse; C486242:Apbb1 protein, rat; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D019151:Peptide Library; D019000:Phosphotyrosine