PMID- 10341243 OWN - NLM STAT- MEDLINE DCOM- 19990616 LR - 20191023 IS - 1529-2401 (Electronic) IS - 0270-6474 (Linking) VI - 19 IP - 11 DP - 1999 Jun 1 TI - Role of phosphorylation of Alzheimer's amyloid precursor protein during neuronal differentiation. PG - 4421-7 AB - Alzheimer's amyloid precursor protein (APP), the precursor of beta-amyloid (Abeta), is an integral membrane protein with a receptor-like structure. We recently demonstrated that the mature APP (mAPP; N- and O-glycosylated form) is phosphorylated at Thr668 (numbering for APP695 isoform), specifically in neurons. Phosphorylation of mAPP appears to occur during, and after, neuronal differentiation. Here we report that the phosphorylation of mAPP begins 48-72 hr after treatment of PC12 cells with NGF and that this correlates with the timing of neurite outgrowth. The phosphorylated form of APP is distributed in neurites and mostly in the growth cones of differentiating PC12 cells. PC12 cells stably expressing APP with Thr668Glu substitution showed remarkably reduced neurite extension after treatment with NGF. These observations suggest that the phosphorylated form of APP may play an important role in neurite outgrowth of differentiating neurons. FAU - Ando, K AU - Ando K AD - Laboratory of Neurobiophysics, School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033 Japan. FAU - Oishi, M AU - Oishi M FAU - Takeda, S AU - Takeda S FAU - Iijima, K AU - Iijima K FAU - Isohara, T AU - Isohara T FAU - Nairn, A C AU - Nairn AC FAU - Kirino, Y AU - Kirino Y FAU - Greengard, P AU - Greengard P FAU - Suzuki, T AU - Suzuki T LA - eng GR - P01 AG009464/AG/NIA NIH HHS/United States GR - AG09464/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Nerve Tissue Proteins) RN - 2ZD004190S (Threonine) SB - IM MH - Alzheimer Disease/*metabolism/pathology MH - Amyloid beta-Protein Precursor/genetics/*physiology MH - Animals MH - Cell Differentiation/physiology MH - Mutation MH - Nerve Tissue Proteins/genetics/*physiology MH - Neurons/*metabolism/pathology MH - PC12 Cells MH - Phosphorylation MH - Rats MH - Threonine/physiology PMC - PMC6782598 EDAT- 1999/05/26 00:00 MHDA- 1999/05/26 00:01 CRDT- 1999/05/26 00:00 PHST- 1999/05/26 00:00 [pubmed] PHST- 1999/05/26 00:01 [medline] PHST- 1999/05/26 00:00 [entrez] PST - ppublish SO - J Neurosci. 1999 Jun 1;19(11):4421-7.