QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (67) Citing Articles via Google Scholar Google Scholar Articles by Ando, K. Articles by Suzuki, T. Search for Related Content PubMed PubMed Citation Articles by Ando, K. Articles by Suzuki, T.

 Previous Article  |  Next Article 

The Journal of Neuroscience, June 1, 1999, 19(11):4421-4427

Role of Phosphorylation of Alzheimer's Amyloid Precursor Protein during Neuronal Differentiation

Kanae Ando¹, Masaki Oishi², Shizu Takeda^{1, 3}, Ko-ichi Iijima¹, Toshio Isohara^{2, 4}, Angus C. Nairn², Yutaka Kirino¹, Paul Greengard², and Toshiharu Suzuki¹

¹ Laboratory of Neurobiophysics, School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033 Japan, ² Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York, 10021, ³ Bio-oriented Technology Research Advancement Institution, Toranomon 3-18-19, Minato-ku, Tokyo 105-0001, Japan, and ⁴ Life Science Research Center, Advanced Technology Research Laboratories, Nippon Steel Corporation, 3-35-1 Ida, Nakahara-ku, Kawasaki 211-0035, Japan

Alzheimer's amyloid precursor protein (APP), the precursor of -amyloid (A), 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.

Key words: Alzheimer's disease; amyloid precursor protein; neurite outgrowth; protein phosphorylation; PC12 cells; neuronal differentiation

---

Copyright © 1999 Society for Neuroscience  0270-6474/99/19114421-07$05.00/0

This article has been cited by other articles:

				T. Suzuki and T. Nakaya Regulation of Amyloid {beta}-Protein Precursor by Phosphorylation and Protein Interactions J. Biol. Chem., October 31, 2008; 283(44): 29633 - 29637. [Abstract] [Full Text] [PDF]

				T. Hoshino, T. Nakaya, T. Homan, K.-i. Tanaka, Y. Sugimoto, W. Araki, M. Narita, S. Narumiya, T. Suzuki, and T. Mizushima Involvement of Prostaglandin E2 in Production of Amyloid-beta Peptides Both in Vitro and in Vivo J. Biol. Chem., November 9, 2007; 282(45): 32676 - 32688. [Abstract] [Full Text] [PDF]

				Z. Muresan and V. Muresan The Amyloid-beta Precursor Protein Is Phosphorylated via Distinct Pathways during Differentiation, Mitosis, Stress, and Degeneration Mol. Biol. Cell, October 1, 2007; 18(10): 3835 - 3844. [Abstract] [Full Text] [PDF]

				A. Marutle, M. Ohmitsu, M. Nilbratt, N. H. Greig, A. Nordberg, and K. Sugaya Modulation of human neural stem cell differentiation in Alzheimer (APP23) transgenic mice by phenserine PNAS, July 24, 2007; 104(30): 12506 - 12511. [Abstract] [Full Text] [PDF]

				E. Rockenstein, M. Torrance, A. Adame, M. Mante, P. Bar-on, J. B. Rose, L. Crews, and E. Masliah Neuroprotective Effects of Regulators of the Glycogen Synthase Kinase-3{beta} Signaling Pathway in a Transgenic Model of Alzheimer's Disease Are Associated with Reduced Amyloid Precursor Protein Phosphorylation J. Neurosci., February 21, 2007; 27(8): 1981 - 1991. [Abstract] [Full Text] [PDF]

				Z. Muresan and V. Muresan Neuritic Deposits of Amyloid-{beta} Peptide in a Subpopulation of Central Nervous System-Derived Neuronal Cells. Mol. Cell. Biol., July 1, 2006; 26(13): 4982 - 4997. [Abstract] [Full Text] [PDF]

				K.-A Chang, H.-S. Kim, T.-Y. Ha, J.-W. Ha, K. Y. Shin, Y. H. Jeong, J.-P. Lee, C.-H. Park, S. Kim, T.-K. Baik, et al. Phosphorylation of Amyloid Precursor Protein (APP) at Thr668 Regulates the Nuclear Translocation of the APP Intracellular Domain and Induces Neurodegeneration. Mol. Cell. Biol., June 1, 2006; 26(11): 4327 - 4338. [Abstract] [Full Text] [PDF]

				T. Nakaya and T. Suzuki Role of APP phosphorylation in FE65-dependent gene transactivation mediated by AICD Genes Cells, June 1, 2006; 11(6): 633 - 645. [Abstract] [Full Text] [PDF]

				A. Sumioka, S. Nagaishi, T. Yoshida, A. Lin, M. Miura, and T. Suzuki Role of 14-3-3{gamma} in FE65-dependent Gene Transactivation Mediated by the Amyloid {beta}-Protein Precursor Cytoplasmic Fragment J. Biol. Chem., December 23, 2005; 280(51): 42364 - 42374. [Abstract] [Full Text] [PDF]

				Z. Muresan and V. Muresan Coordinated transport of phosphorylated amyloid-{beta} precursor protein and c-Jun NH2-terminal kinase-interacting protein-1 J. Cell Biol., November 21, 2005; 171(4): 615 - 625. [Abstract] [Full Text] [PDF]

				E. Rockenstein, M. Mante, M. Alford, A. Adame, L. Crews, M. Hashimoto, L. Esposito, L. Mucke, and E. Masliah High {beta}-Secretase Activity Elicits Neurodegeneration in Transgenic Mice Despite Reductions in Amyloid-{beta} Levels: IMPLICATIONS FOR THE TREATMENT OF ALZHEIMER DISEASE J. Biol. Chem., September 23, 2005; 280(38): 32957 - 32967. [Abstract] [Full Text] [PDF]

				W. T. Kimberly, J. B. Zheng, T. Town, R. A. Flavell, and D. J. Selkoe Physiological Regulation of the {beta}-Amyloid Precursor Protein Signaling Domain by c-Jun N-Terminal Kinase JNK3 during Neuronal Differentiation J. Neurosci., June 8, 2005; 25(23): 5533 - 5543. [Abstract] [Full Text] [PDF]

				Z. Muresan and V. Muresan c-Jun NH2-Terminal Kinase-Interacting Protein-3 Facilitates Phosphorylation and Controls Localization of Amyloid-{beta} Precursor Protein J. Neurosci., April 13, 2005; 25(15): 3741 - 3751. [Abstract] [Full Text] [PDF]

				M. Asaumi, K. Iijima, A. Sumioka, K. Iijima-Ando, Y. Kirino, T. Nakaya, and T. Suzuki Interaction of N-Terminal Acetyltransferase with the Cytoplasmic Domain of {beta}-Amyloid Precursor Protein and Its Effect on A{beta} Secretion J. Biochem., February 1, 2005; 137(2): 147 - 155. [Abstract] [Full Text] [PDF]

				E. B. Lee, B. Zhang, K. Liu, E. A. Greenbaum, R. W. Doms, J. Q. Trojanowski, and V. M.-Y. Lee BACE overexpression alters the subcellular processing of APP and inhibits A{beta} deposition in vivo J. Cell Biol., January 17, 2005; 168(2): 291 - 302. [Abstract] [Full Text] [PDF]

				H. Taru and T. Suzuki Facilitation of Stress-induced Phosphorylation of {beta}-Amyloid Precursor Protein Family Members by X11-like/Mint2 Protein J. Biol. Chem., May 14, 2004; 279(20): 21628 - 21636. [Abstract] [Full Text] [PDF]

				Z. Muresan and V. Muresan A phosphorylated, carboxy-terminal fragment of {beta}-amyloid precursor protein localizes to the splicing factor compartment Hum. Mol. Genet., March 1, 2004; 13(5): 475 - 488. [Abstract] [Full Text] [PDF]

				Y. Araki, S. Tomita, H. Yamaguchi, N. Miyagi, A. Sumioka, Y. Kirino, and T. Suzuki Novel Cadherin-related Membrane Proteins, Alcadeins, Enhance the X11-like Protein-mediated Stabilization of Amyloid {beta}-Protein Precursor Metabolism J. Biol. Chem., December 5, 2003; 278(49): 49448 - 49458. [Abstract] [Full Text] [PDF]

				S. Kins, P. Kurosinski, R. M. Nitsch, and J. Gotz Activation of the ERK and JNK Signaling Pathways Caused by Neuron-Specific Inhibition of PP2A in Transgenic Mice Am. J. Pathol., September 1, 2003; 163(3): 833 - 843. [Abstract] [Full Text] [PDF]

				H. Inomata, Y. Nakamura, A. Hayakawa, H. Takata, T. Suzuki, K. Miyazawa, and N. Kitamura A Scaffold Protein JIP-1b Enhances Amyloid Precursor Protein Phosphorylation by JNK and Its Association with Kinesin Light Chain 1 J. Biol. Chem., June 13, 2003; 278(25): 22946 - 22955. [Abstract] [Full Text] [PDF]

				B. J. Schnapp Trafficking of signaling modules by kinesin motors J. Cell Sci., June 1, 2003; 116(11): 2125 - 2135. [Abstract] [Full Text] [PDF]

				G. V. Gassen and W. Annaert Amyloid, Presenilins, and Alzheimer's Disease Neuroscientist, April 1, 2003; 9(2): 117 - 126. [Abstract] [PDF]

				H. Taru, Y. Kirino, and T. Suzuki Differential Roles of JIP Scaffold Proteins in the Modulation of Amyloid Precursor Protein Metabolism J. Biol. Chem., July 19, 2002; 277(30): 27567 - 27574. [Abstract] [Full Text] [PDF]

				H. Taru, K.-i. Iijima, M. Hase, Y. Kirino, Y. Yagi, and T. Suzuki Interaction of Alzheimer's beta -Amyloid Precursor Family Proteins with Scaffold Proteins of the JNK Signaling Cascade J. Biol. Chem., May 24, 2002; 277(22): 20070 - 20078. [Abstract] [Full Text] [PDF]

				K. Ando, K.-i. Iijima, J. I. Elliott, Y. Kirino, and T. Suzuki Phosphorylation-dependent Regulation of the Interaction of Amyloid Precursor Protein with Fe65 Affects the Production of beta -Amyloid J. Biol. Chem., October 19, 2001; 276(43): 40353 - 40361. [Abstract] [Full Text] [PDF]

				J. Walter, A. Schindzielorz, B. Hartung, and C. Haass Phosphorylation of the beta -Amyloid Precursor Protein at the Cell Surface by Ectocasein Kinases 1 and 2 J. Biol. Chem., July 28, 2000; 275(31): 23523 - 23529. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help