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 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.
Suzuki
T
T
Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan. t-suzuki@mayqueen.f.u-tokyo.ac.jp
Ando
K
K
Isohara
T
T
Oishi
M
M
Lim
G S
GS
Satoh
Y
Y
Wasco
W
W
Tanzi
R E
RE
Nairn
A C
AC
Greengard
P
P
Gandy
S E
SE
Kirino
Y
Y
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
C489697:APLP1 protein, human; C084104:APLP2 protein, human; D016564:Amyloid beta-Protein Precursor; C498283:Aplp2 protein, rat; D009419:Nerve Tissue Proteins