title: Phosphorylation of Alzheimer beta-amyloid precursor-like proteins.
abstract: Amyloid precursor-like proteins (APLPs), APLP1 and APLP2, are members of a gene family which include the Alzheimer beta-amyloid precursor protein (APP). APLP1, APLP2, and APP contain highly homologous amino acid sequences, especially in their cytoplasmic domains, although APLPs lack the beta-amyloid domain derived by proteolytic processing from APP. APP is phosphorylated at three sites in the cytoplasmic domain in cultured cells and adult rat brain [Suzuki et al. (1994) EMBO J. 13, 1114-1122; Oishi, et al. (1997) Mol. 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, 534-542; Walter et al. (1997) J. Biol. Chem. 272, 1896-1903]. We report here that a cytoplasmic domain peptide from APLP1 is phosphorylated in 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 cdc2 kinase site phosphorylated in APP. Furthermore, phosphorylation of this site occurs in a cell cycle-dependent manner in cultured cells. These findings indicate that in intact cells the phosphorylation of APLP2 appears to be regulated in a similar fashion to that of APP.
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan. t-suzuki@mayqueen.f.u-tokyo.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Ando
authors.forename: T
authors.initials: T
authors.lastname: Isohara
authors.forename: M
authors.initials: M
authors.lastname: Oishi
authors.forename: G S
authors.initials: GS
authors.lastname: Lim
authors.forename: Y
authors.initials: Y
authors.lastname: Satoh
authors.forename: W
authors.initials: W
authors.lastname: Wasco
authors.forename: R E
authors.initials: RE
authors.lastname: Tanzi
authors.forename: A C
authors.initials: AC
authors.lastname: Nairn
authors.forename: P
authors.initials: P
authors.lastname: Greengard
authors.forename: S E
authors.initials: SE
authors.lastname: Gandy
authors.forename: Y
authors.initials: Y
authors.lastname: Kirino
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000031:analogs & derivatives / Q000378:metabolism*; D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D005910:Glioma; D006367:HeLa Cells; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: C489697:APLP1 protein, human; C084104:APLP2 protein, human; D016564:Amyloid beta-Protein Precursor; C498283:Aplp2 protein, rat; D009419:Nerve Tissue Proteins