Advertisement
JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M500833200 on July 14, 2005 Originally published In Press as doi:10.1074/jbc.M500833200 on July 13, 2005

J. Biol. Chem., Vol. 280, Issue 36, 31537-31547, September 9, 2005
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Data
Right arrow All Versions of this Article:
280/36/31537    most recent
M500833200v2
M500833200v1
Right arrow Submit a Letter to Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kang, D. E.
Right arrow Articles by Koo, E. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kang, D. E.
Right arrow Articles by Koo, E. H.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Presenilins Mediate Phosphatidylinositol 3-Kinase/AKT and ERK Activation via Select Signaling Receptors

SELECTIVITY OF PS2 IN PLATELET-DERIVED GROWTH FACTOR SIGNALING*{boxs}

David E. Kang{ddagger}, Il Sang Yoon, Emanuela Repetto, Tracy Busse, Nader Yermian, Listya Ie, and Edward H. Koo

From the Department of Neurosciences, University of California, San Diego, La Jolla, California 92093

The Alzheimer's disease-linked genes, PS1 and PS2, are required for intramembrane proteolysis of multiple type I proteins, including Notch and amyloid precursor protein. In addition, it has been documented that PS1 positively regulates, whereas PS1 familial Alzheimer disease mutations suppress, phosphatidylinositol 3-kinase (PI3K)/Akt activation, a pathway known to inactivate glycogen synthase kinase-3 and reduce tau phosphorylation. In this study, we show that the loss of presenilins not only inhibits PI3K/Akt signaling and increases tau phosphorylation but also suppresses the MEK/ERK pathway. The deficits in Akt and ERK activation in cells deficient in both PS1 and PS2 (PS–/–) are evident after serum withdrawal and stimulation with fetal bovine serum or ligands of select receptor tyrosine kinases, platelet-derived growth factor receptor {beta} (PDGFR{beta}) and PDGFR{alpha}, but not insulin-like growth factor-1R and epidermal growth factor receptor. The defects in PDGF signaling in PS–/– cells are due to reduced expression of PDGF receptors. Whereas fetal bovine serum-induced Akt activation is reconstituted by both PS1 and PS2 in PS–/– cells, PDGF signaling is selectively restored by PS2 but not PS1 and is dependent on the N-terminal fragment of PS2 but not {gamma}-secretase activity or the hydrophilic loop of PS2. The rescue of PDGF receptor expression and activation by PS2 is facilitated by FHL2, a PS2-interacting transcriptional co-activator. Finally, we present evidence that PS1 mutations interfere with this PS2-mediated activity by reducing PS2 fragments. These findings highlight important roles of both presenilins in Akt and ERK signaling via select signaling receptors.

Received for publication, January 24, 2005 , and in revised form, June 8, 2005.

* This work was supported in part by the American Federation for Aging Research (to D. E. K.) and Alzheimer's Association Grant NIRG-02-4044 (to D. E. K.). Parts of this paper were presented at the 9th International Conference on Alzheimer's Disease and Related Disorders, July 17–22, 2004, Philadelphia, and published in abstract form (54). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{boxs} The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. 1–3.

{ddagger} To whom correspondence should be addressed: Dept. of Neurosciences, UC San Diego, Leichtag Biomedical Research 380, 9500 Gilman Dr., La Jolla, CA 92093. Tel.: 858-822-6484; Fax: 858-822-1021; E-mail: dekang{at}ucsd.edu.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
H. Watanabe, M. J. Smith, E. Heilig, V. Beglopoulos, R. J. Kelleher III, and J. Shen
Indirect Regulation of Presenilins in CREB-mediated Transcription
J. Biol. Chem., May 15, 2009; 284(20): 13705 - 13713.
[Abstract] [Full Text] [PDF]

Home page
 AM J ALZHEIMERS DIS OTHER DEMENHome page
A. Robles, M.J. Sobrido, M. Garcia-Murias, J.M. Prieto, M. Lema, D. Santos, and M. Paramo
Clinical Picture of a Patient With a Novel PSEN1 Mutation (L424V)
American Journal of Alzheimer's Disease and Other Dementias, February 1, 2009; 24(1): 40 - 45.
[Abstract] [PDF]

Home page
 J. Neurosci.Home page
S. Oddo, A. Caccamo, B. Tseng, D. Cheng, V. Vasilevko, D. H. Cribbs, and F. M. LaFerla
Blocking A{beta}42 Accumulation Delays the Onset and Progression of Tau Pathology via the C Terminus of Heat Shock Protein70-Interacting Protein: A Mechanistic Link between A{beta} and Tau Pathology
J. Neurosci., November 19, 2008; 28(47): 12163 - 12175.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
V. Kallhoff-Munoz, L. Hu, X. Chen, R. G. Pautler, and H. Zheng
Genetic Dissection of {gamma}-Secretase-Dependent and-Independent Functions of Presenilin in Regulating Neuronal Cell Cycle and Cell Death
J. Neurosci., October 29, 2008; 28(44): 11421 - 11431.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
D. Spasic and W. Annaert
Building {gamma}-secretase - the bits and pieces
J. Cell Sci., February 15, 2008; 121(4): 413 - 420.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
L. Baki, R. L. Neve, Z. Shao, J. Shioi, A. Georgakopoulos, and N. K Robakis
Wild-Type But Not FAD Mutant Presenilin-1 Prevents Neuronal Degeneration by Promoting Phosphatidylinositol 3-Kinase Neuroprotective Signaling
J. Neurosci., January 9, 2008; 28(2): 483 - 490.
[Abstract] [Full Text] [PDF]

Home page
 Annals of Clinical & Laboratory ScienceHome page
W. Feng, R. E. Brown, C. D. Trung, W. Li, L. Wang, T. Khoury, S. Alrawi, J. Yao, K. Xia, and D. Tan
Morphoproteomic Profile of mTOR, Ras/Raf Kinase/ERK, and NF-{kappa}B Pathways in Human Gastric Adenocarcinoma
Ann. Clin. Lab. Sci., January 1, 2008; 38(3): 195 - 209.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
A. Li, Z. Xie, Y. Dong, K. M. McKay, M. L. McKee, and R. E. Tanzi
Isolation and characterization of the Drosophila ubiquilin ortholog dUbqln: in vivo interaction with early-onset Alzheimer disease genes
Hum. Mol. Genet., November 1, 2007; 16(21): 2626 - 2639.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Repetto, I.-S. Yoon, H. Zheng, and D. E. Kang
Presenilin 1 Regulates Epidermal Growth Factor Receptor Turnover and Signaling in the Endosomal-Lysosomal Pathway
J. Biol. Chem., October 26, 2007; 282(43): 31504 - 31516.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. Khandelwal, D. Chandu, C. M. Roe, R. Kopan, and R. S. Quatrano
Moonlighting activity of presenilin in plants is independent of {gamma}-secretase and evolutionarily conserved
PNAS, August 14, 2007; 104(33): 13337 - 13342.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Nizzari, V. Venezia, E. Repetto, V. Caorsi, R. Magrassi, M. C. Gagliani, P. Carlo, T. Florio, G. Schettini, C. Tacchetti, et al.
Amyloid Precursor Protein and Presenilin1 Interact with the Adaptor GRB2 and Modulate ERK 1,2 Signaling
J. Biol. Chem., May 4, 2007; 282(18): 13833 - 13844.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
N. Landman, S. Y. Jeong, S. Y. Shin, S. V. Voronov, G. Serban, M. S. Kang, M. K. Park, G. Di Paolo, S. Chung, and T.-W. Kim
Presenilin mutations linked to familial Alzheimer's disease cause an imbalance in phosphatidylinositol 4,5-bisphosphate metabolism
PNAS, December 19, 2006; 103(51): 19524 - 19529.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
S. Chiba
Concise Review: Notch Signaling in Stem Cell Systems
Stem Cells, November 1, 2006; 24(11): 2437 - 2447.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
C. Alves da Costa, C. Sunyach, R. Pardossi-Piquard, J. Sevalle, B. Vincent, N. Boyer, T. Kawarai, N. Girardot, P. St. George-Hyslop, and F. Checler
Presenilin-dependent gamma-secretase-mediated control of p53-associated cell death in Alzheimer's disease.
J. Neurosci., June 7, 2006; 26(23): 6377 - 6385.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
Y. Niu, F. Roy, F. Saltel, C. Andrieu-Soler, W. Dong, A.-L. Chantegrel, R. Accardi, A. Thepot, N. Foiselle, M. Tommasino, et al.
A nuclear export signal and phosphorylation regulate dok1 subcellular localization and functions.
Mol. Cell. Biol., June 1, 2006; 26(11): 4288 - 4301.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
R. Wang, Y.-w. Zhang, X. Zhang, R. Liu, X. Zhang, S. Hong, K. Xia, J. Xia, Z. Zhang, and H. Xu
Transcriptional regulation of APH-1A and increased {gamma}-secretase cleavage of APP and Notch by HIF-1 and hypoxia
FASEB J, June 1, 2006; 20(8): 1275 - 1277.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Tanemura, D.-H. Chui, T. Fukuda, M. Murayama, J.-M. Park, T. Akagi, Y. Tatebayashi, T. Miyasaka, T. Kimura, T. Hashikawa, et al.
Formation of Tau Inclusions in Knock-in Mice with Familial Alzheimer Disease (FAD) Mutation of Presenilin 1 (PS1)
J. Biol. Chem., February 24, 2006; 281(8): 5037 - 5041.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
R. Wang, Y.-w. Zhang, P. Sun, R. Liu, X. Zhang, X. Zhang, K. Xia, J. Xia, H. Xu, and Z. Zhang
Transcriptional Regulation of PEN-2, a Key Component of the {gamma}-Secretase Complex, by CREB
Mol. Cell. Biol., February 15, 2006; 26(4): 1347 - 1354.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2005 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement