Beta-amyloid precursor protein is modified with O-linked N-acetylglucosamine.
The beta-amyloid precursor protein (APP) has been implicated in the etiology of Alzheimer's disease (Kang et al.: Nature 325:733-736, 1987; Selkoe: Science 248:1058-1060, 1990; Selkoe: In Cowan et al. (eds): "Annual Review of Neuroscience." Palo Alto, CA: Annual Reviews, Inc., pp 489-519, 1994) and numerous studies have shown that beta-amyloid is involved in amyloid plaque formation (Rumble et al.: N Engl J Med 320:1446-1452, 1989; Sisodia et al.: Science 248: 492-495, 1990). Evidence is presented that APP is modified with N-acetylglucosamine linked to cytoplasmic serine or threonine residues (O-GlcNAc). This is the first report of a plasma membrane protein modified with this carbohydrate. It has been postulated that this modification, which is ubiquitous in all organisms studied to date except bacteria (Haltiwanger et al.: Biochem Soc Trans 20:264-269, 1992; Dong et al.: J Biol Chem 268:16679-16687, 1993; Elliot et al.: J Neurosci 13:2424-2429, 1993; Kelly et al.: J Biol Chem 268:10416-10424, 1993), may function as an alternative to phosphorylation (Dong et al., 1993) and is involved in the multimerization of proteins (Haltiwanger et al., 1992; Dong et al., 1993). O-GlcNAc occurs at "PEST" sequences (Rogers et al.: Science 234:364-368, 1986) and it has been suggested that this modification within such a sequence leads to increased proteolytic stability of the molecule (Dong et al., 1993).(ABSTRACT TRUNCATED AT 250 WORDS)
Griffith
L S
LS
Department of Biochemistry, Rheinische Friedrich-Wilhelms University, Bonn, Germany.
Mathes
M
M
Schmitz
B
B
D000117:Acetylglucosamine / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002241:Carbohydrates / Q000494:pharmacology; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects*; D005690:Galactose / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008815:Mice, Inbred Strains; D011233:Precipitin Tests
D016564:Amyloid beta-Protein Precursor; D000911:Antibodies, Monoclonal; D002241:Carbohydrates; D000117:Acetylglucosamine; D005690:Galactose