FE65L2 - A NEW MEMBER OF THE FE65 PROTEIN FAMILY INTERACTING WITH THEINTRACELLULAR DOMAIN OF THE ALZHEIMERS BETA-AMYLOID PRECURSOR PROTEIN

We previously demonstrated that Fe65 protein is one of the ligands of the cytoplasmic domain of beta-amyloid precursor protein (APP). Anothe r ligand of this molecule was recently identified; it is similar to Fe 65, so it was named Fe65-like (Fe65L1). Herein we describe the cloning of another Fe65-like cDNA (Fe65L2), similar to Fe65 and to Fe65L1, wh ich encodes a protein of approx. 50 kDa. Its cognate mRNA is expressed in various rat tissues, particularly in brain and testis. The three m embers of the Fe65 protein family share several structural and functio nal characteristics. The primary structures of the three proteins can be aligned in three regions corresponding to the protein-protein inter action domains of Fe65 [the protein-protein interaction domain contain ing two conserved tryptophan residues and the two phosphotyrosine inte raction domain/phosphotyrosine binding (PID/PTB) domains], whereas the remaining sequences are poorly related. Like Fe65, Fe65L1 and Fe65L2 genes encode two different protein isoforms, derived from the alternat ive splicing of a very small exon of only six nucleotides, which resul ts, within the N-terminal PID/PTB domain, in the presence or absence o f two acidic/basic amino acids. Fe65L2 is able to interact, both in vi tro and in vivo, with the intracellular domain of APP. Also, in the ca se of APP, another two closely related proteins exist, named beta-amyl oid precursor-like protein (APLP)1 and APLP2: by using the interaction trap procedure we observed that both Fe65 and Fe65L2 interact with AP P, APLP 1 or APLP2, although with different efficiencies.