 |
||||
|
||||
|
||||
|
||||
|
||||
Previous Article | Next Article
The Journal of Neuroscience, February 15, 2003, 23(4):1189
Developmental Regulation of the Proteolysis of the p35 Cyclin-Dependent Kinase 5 Activator by Phosphorylation
Taro Saito1, Reiko Onuki1, Yuichi Fujita1, Gen-ichi Kusakawa1, 2, Koichi Ishiguro3, James A. Bibb4, Takeo Kishimoto2, and Shin-ichi Hisanaga1 1 Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Minami-Osawa, Hachiohji, Tokyo 192-0397, Japan, 2 Laboratory of Cell and Developmental Biology, Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan, 3 Mitsubishi Kasei Institute of Life Sciences, Machida, Tokyo 194-8511, Japan, and 4 Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas 75390
Cyclin-dependent kinase 5 (Cdk5), a cdc2-related kinase expressed in postmitotic neurons, is activated by association with a brain-specific activator, p35. It has been suggested that the conversion of p35 to p25 by the protease calpain is involved in neuronal cell death. However, p35 protein is turned over rapidly via proteasomal degradation in living neurons. In this study we show that the phosphorylation of p35 by Cdk5 suppresses the cleavage to p25 by calpain, whereas phosphorylation facilitates the proteasomal degradation of p35. The phosphorylation site in p35 that might be involved in preventing calpain cleavage was distinct from the phosphorylation site involved in facilitating proteasomal degradation. A phosphorylated form of p35 that was resistant to cleavage by calpain was more prevalent in the fetal brain, whereas the unphosphorylated form of p35 occurred in the adult brain. These results suggest that the phosphorylation of p35 serves as a protective mechanism that suppresses the generation of p25 in developing brains.
Key words: calpain; Cdk5; neuron; proteasome; protein kinase; cell death; development
Copyright © 2003 Society for Neuroscience 0270-6474/03/2341189-09$05.00/0
This article has been cited by other articles:
K. Yotsumoto, T. Saito, A. Asada, T. Oikawa, T. Kimura, C. Uchida, K. Ishiguro, T. Uchida, M. Hasegawa, and S.-i. Hisanaga
Effect of Pin1 or Microtubule Binding on Dephosphorylation of FTDP-17 Mutant Tau
J. Biol. Chem., June 19, 2009; 284(25): 16840 - 16847.
[Abstract] [Full Text] [PDF]
S. Kaminosono, T. Saito, F. Oyama, T. Ohshima, A. Asada, Y. Nagai, N. Nukina, and S.-i. Hisanaga
Suppression of Mutant Huntingtin Aggregate Formation by Cdk5/p35 through the Effect on Microtubule Stability
J. Neurosci., August 27, 2008; 28(35): 8747 - 8755.
[Abstract] [Full Text] [PDF]
L. He, Z. Hou, and R. Z. Qi
Calmodulin Binding and Cdk5 Phosphorylation of p35 Regulate Its Effect on Microtubules
J. Biol. Chem., May 9, 2008; 283(19): 13252 - 13260.
[Abstract] [Full Text] [PDF]
C. Naujokat and T. Saric
Concise Review: Role and Function of the Ubiquitin-Proteasome System in Mammalian Stem and Progenitor Cells
Stem Cells, October 1, 2007; 25(10): 2408 - 2418.
[Abstract] [Full Text] [PDF]
C. Nguyen, A. Nishi, J. W. Kansy, J. Fernandez, K. Hayashi, F. Gillardon, H. C. Hemmings Jr., A. C. Nairn, and J. A. Bibb
Regulation of Protein Phosphatase Inhibitor-1 by Cyclin-dependent Kinase 5
J. Biol. Chem., June 1, 2007; 282(22): 16511 - 16520.
[Abstract] [Full Text] [PDF]
H. Kamei, T. Saito, M. Ozawa, Y. Fujita, A. Asada, J. A. Bibb, T. C. Saido, H. Sorimachi, and S.-i. Hisanaga
Suppression of Calpain-dependent Cleavage of the CDK5 Activator p35 to p25 by Site-specific Phosphorylation
J. Biol. Chem., January 19, 2007; 282(3): 1687 - 1694.
[Abstract] [Full Text] [PDF]
B. Sahin, H. Shu, J. Fernandez, A. El-Armouche, J. D. Molkentin, A. C. Nairn, and J. A. Bibb
Phosphorylation of Protein Phosphatase Inhibitor-1 by Protein Kinase C
J. Biol. Chem., August 25, 2006; 281(34): 24322 - 24335.
[Abstract] [Full Text] [PDF]
F. Sakaue, T. Saito, Y. Sato, A. Asada, K. Ishiguro, M. Hasegawa, and S.-i. Hisanaga
Phosphorylation of FTDP-17 Mutant tau by Cyclin-dependent Kinase 5 Complexed with p35, p25, or p39
J. Biol. Chem., September 9, 2005; 280(36): 31522 - 31529.
[Abstract] [Full Text] [PDF]
S. Sasaki, D. Mori, K. Toyo-oka, A. Chen, L. Garrett-Beal, M. Muramatsu, S. Miyagawa, N. Hiraiwa, A. Yoshiki, A. Wynshaw-Boris, et al.
Complete Loss of Ndel1 Results in Neuronal Migration Defects and Early Embryonic Lethality
Mol. Cell. Biol., September 1, 2005; 25(17): 7812 - 7827.
[Abstract] [Full Text] [PDF]
M. Futter, K. Uematsu, S. A. Bullock, Y. Kim, H. C. Hemmings Jr., A. Nishi, P. Greengard, and A. C. Nairn
Phosphorylation of spinophilin by ERK and cyclin-dependent PK 5 (Cdk5)
PNAS, March 1, 2005; 102(9): 3489 - 3494.
[Abstract] [Full Text] [PDF]
A. C. B. Lim, Z. Hou, C.-P. Goh, and R. Z. Qi
Protein Kinase CK2 Is an Inhibitor of the Neuronal Cdk5 Kinase
J. Biol. Chem., November 5, 2004; 279(45): 46668 - 46673.
[Abstract] [Full Text] [PDF]
A. Izquierdo, R. K. Suda, and E. A. Murray
Bilateral Orbital Prefrontal Cortex Lesions in Rhesus Monkeys Disrupt Choices Guided by Both Reward Value and Reward Contingency
J. Neurosci., August 25, 2004; 24(34): 7540 - 7548.
[Abstract] [Full Text] [PDF]
S. Y. Lee, M. R. Wenk, Y. Kim, A. C. Nairn, and P. De Camilli
Regulation of synaptojanin 1 by cyclin-dependent kinase 5 at synapses
PNAS, January 13, 2004; 101(2): 546 - 551.
[Abstract] [Full Text] [PDF]
K. Tomizawa, S. Sunada, Y.-F. Lu, Y. Oda, M. Kinuta, T. Ohshima, T. Saito, F.-Y. Wei, M. Matsushita, S.-T. Li, et al.
Cophosphorylation of amphiphysin I and dynamin I by Cdk5 regulates clathrin-mediated endocytosis of synaptic vesicles
J. Cell Biol., November 24, 2003; 163(4): 813 - 824.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|