Phosphorylation of Alzheimer beta-amyloid precursor-like proteins

Biochemistry. 1997 Apr 15;36(15):4643-9. doi: 10.1021/bi962618k.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amyloid beta-Protein Precursor / analogs & derivatives
  • Amyloid beta-Protein Precursor / metabolism*
  • Animals
  • Cytoplasm / metabolism
  • Glioma
  • HeLa Cells
  • Humans
  • Nerve Tissue Proteins / metabolism
  • Phosphorylation
  • Protein Structure, Tertiary
  • Rats
  • Tumor Cells, Cultured


  • APLP1 protein, human
  • APLP2 protein, human
  • Amyloid beta-Protein Precursor
  • Aplp2 protein, rat
  • Nerve Tissue Proteins