Cell surface receptor function of amyloid precursor protein that activates Ser/Thr kinases.
Amyloid precursor protein (APP) has been shown to serve as a G(o)-coupled receptor in cell-free systems [Okamoto et al: J Biol Chem 1995;270:4205-4208]. However, it has not been known whether APP exerts intracellular signaling functions in living cells. In this study, we show that stimulation of APP by anti-APP antibody as well as by a mutation found in familial Alzheimer's disease results in activation of a specific set of mitogen-activated protein kinases in multiple vertebrate cells. We conclude that APP acts as a cell surface receptor of biological relevance that turns on specific Ser/Thr kinases, and suggest that the signaling function of APP is a potential target of familial Alzheimer's disease mutations.
Murayama
Y
Y
Forth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.
Takeda
S
S
Yonezawa
K
K
Giambarella
U
U
Nishimoto
I
I
Ogata
E
E
D000544:Alzheimer Disease / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D019556:COS Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002999:Clone Cells; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D005910:Glioma / Q000201:enzymology / Q000473:pathology; D007267:Injections; D019950:Mitogen-Activated Protein Kinase 1; D009154:Mutation; D009865:Oocytes; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D018075:RNA, Complementary / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014981:Xenopus
D016564:Amyloid beta-Protein Precursor; D000906:Antibodies; D018075:RNA, Complementary; D011956:Receptors, Cell Surface; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1