PHOSPHORYLATION OF ALZHEIMER BETA-AMYLOID PRECURSOR-LIKE PROTEINS

Amyloid precursor-like proteins (APLPs), APLP1 and APLP2, are members of a gene family which include the Alzheimer beta-amyloid precursor pr otein (APP). APLP1, APLP2, and APP contain highly homologous amino aci d sequences, especially in their cytoplasmic domains, although APLPs l ack the beta-amyloid domain derived by proteolytic processing from APP . APP is phosphorylated at three sites in the cytoplasmic domain in cu ltured cells and adult rat brain [Suzuki et al. (1994) EMBO J. 13, 111 4-1122; Oishi, et al. (1997) Mel. Med. 3, 109-121] and at sites in the extracellular domain in cultured cells [Knops et al. (1993) Biochem. Biophys. Res. Commun. 197, 380-385; Hung & Selkoe (1994) EMBO J. 13, 5 34-542; Waiter et al. (1997) J. Biol. Chem. 272, 1896-1903]. We report here that a cytoplasmic domain peptide from APLP1 is phosphorylated i n vitro by protein kinase C and that a cytoplasmic domain peptide from APLP2 is phosphorylated in vitro by protein kinase C and cdc2 kinase. APLP2 is phosphorylated by cdc2 kinase at a site homologous to the cd c2 kinase site phosphorylated in APP. Furthermore, phosphorylation of this site occurs in a cell cycle-dependent manner in cultured cells. T hese findings indicate that in intact cells the phosphorylation of APL P2 appears to be regulated in a similar fashion to that of APP.