title: Serine phosphorylation of the secreted extracellular domain of APP.
abstract: The phosphorylation status of full-length APP (FL-APP) and secreted APP (s-APP) was investigated in stably transfected cells. 32P incorporation was detected in the mature full-length APP both in the absence and presence of phorbol ester. Surprisingly, 32P-phosphate was incorporated in the secreted ectodomain, and this was stable to treatment of the [32P]-phospho-s-APP with a large excess of PNGase F, suggesting that N-linked oligosaccharide sites do not account for phosphate incorporation. Phosphoamino acid analysis of the [32P]-phospho-s-APP resulted in the recovery of [32P]-phosphoserine as the preponderant species. Brefeldin A completely inhibited the release of [32P]-phospho s-APP, but did not inhibit the incorporation of 32P into the FL-APP, suggesting that phosphorylation occurs early in the central vacuolar pathway. It is possible that ectodomain phosphorylation by a novel luminal or extracellular protein kinase may play a role in regulating the metabolic fate of APP.
authors.affiliation: Athena Neurosciences, Inc., South San Francisco, California 94080.
authors.forename: J
authors.initials: J
authors.lastname: Knops
authors.forename: S
authors.initials: S
authors.lastname: Gandy
authors.forename: P
authors.initials: P
authors.lastname: Greengard
authors.forename: I
authors.initials: I
authors.lastname: Lieberburg
authors.forename: S
authors.initials: S
authors.lastname: Sinha
mesh_terms: D000596:Amino Acids / Q000032:analysis; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D010710:Phosphates / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
chemical_list: D000596:Amino Acids; D016564:Amyloid beta-Protein Precursor; D010710:Phosphates; D010750:Phosphoproteins; D010761:Phosphorus Radioisotopes; D011494:Protein Kinases; D013755:Tetradecanoylphorbol Acetate