spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search    

The fully linked HTML version of this article has now been published.
JCS ePress online publication date 14 Mar 2006
doi: 10.1242/jcs.02837

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jcs.02837v1
119/7/1329    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
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 arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Choi, B.-H.
Right arrow Articles by Kim, K.-T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Choi, B.-H.
Right arrow Articles by Kim, K.-T.
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   Add to Twitter  
What's this?

Research Article

Protein kinase C{delta}-mediated proteasomal degradation of MAP kinase phosphatase-1 contributes to glutamate-induced neuronal cell death


Bo-Hwa Choi, Eun-Mi Hur, Jong-Hee Lee, Dong-Jae Jun, and Kyong-Tai Kim*
* Author for correspondence (e-mail: ktk{at}postech.ac.kr)

Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) is a dual-specificity phosphatase that is involved in the regulation of cell survival, differentiation and apoptosis through inactivating MAPKs by dephosphorylation. Here, we provide evidence for a role of MKP-1 in the glutamate-induced cell death of HT22 hippocampal cells and primary mouse cortical neurons. We suggest that, during glutamate-induced oxidative stress, protein kinase C (PKC) {delta} becomes activated and induces sustained activation of extracellular signal-regulated kinase 1/2 (ERK1/2) through a mechanism that involves degradation of MKP-1. Glutamate-induced activation of ERK1/2 was blocked by inhibition of PKC{delta}, confirming that ERK1/2 is regulated by PKC{delta}. Prolonged exposure to glutamate caused reduction in the protein level of MKP-1, which correlated with the sustained activation of ERK1/2. Furthermore, knockdown of endogenous MKP-1 by small interfering (si)RNA resulted in pronounced enhancement of ERK1/2 phosphorylation accompanied by increased cytotoxicity under glutamate exposure. In glutamate-treated cells, MKP-1 was polyubiquitylated and proteasome inhibitors markedly blocked the degradation of MKP-1. Moreover, inhibition of glutamate-induced PKC{delta} activation suppressed the downregulation and ubiquitylation of MKP-1. Taken together, these results demonstrate that activation of PKC{delta} triggers degradation of MKP-1 through the ubiquitin-proteasome pathway, thereby contributing to persistent activation of ERK1/2 under glutamate-induced oxidative toxicity.
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   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
P. Xie, S. Guo, Y. Fan, H. Zhang, D. Gu, and H. Li
Atrogin-1/MAFbx Enhances Simulated Ischemia/Reperfusion-induced Apoptosis in Cardiomyocytes through Degradation of MAPK Phosphatase-1 and Sustained JNK Activation
J. Biol. Chem., February 27, 2009; 284(9): 5488 - 5496.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
Y. Ho, R. Samarasinghe, M. E. Knoch, M. Lewis, E. Aizenman, and D. B. DeFranco
Selective Inhibition of Mitogen-Activated Protein Kinase Phosphatases by Zinc Accounts for Extracellular Signal-Regulated Kinase 1/2-Dependent Oxidative Neuronal Cell Death
Mol. Pharmacol., October 1, 2008; 74(4): 1141 - 1151.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
T. Boutros, E. Chevet, and P. Metrakos
Mitogen-Activated Protein (MAP) Kinase/MAP Kinase Phosphatase Regulation: Roles in Cell Growth, Death, and Cancer
Pharmacol. Rev., September 1, 2008; 60(3): 261 - 310.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. L. Lomonaco, S. Kahana, M. Blass, Y. Brody, H. Okhrimenko, C. Xiang, S. Finniss, P. M. Blumberg, H.-K. Lee, and C. Brodie
Phosphorylation of Protein Kinase C{delta} on Distinct Tyrosine Residues Induces Sustained Activation of Erk1/2 via Down-regulation of MKP-1: ROLE IN THE APOPTOTIC EFFECT OF ETOPOSIDE
J. Biol. Chem., June 20, 2008; 283(25): 17731 - 17739.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
X. Qi and D. Mochly-Rosen
The PKC{delta} -Abl complex communicates ER stress to the mitochondria - an essential step in subsequent apoptosis
J. Cell Sci., March 15, 2008; 121(6): 804 - 813.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
P. Lingor, L. Tonges, N. Pieper, C. Bermel, E. Barski, V. Planchamp, and M. Bahr
ROCK inhibition and CNTF interact on intrinsic signalling pathways and differentially regulate survival and regeneration in retinal ganglion cells
Brain, January 1, 2008; 131(1): 250 - 263.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. K. Venugopal, J. Chen, Y. Zhang, D. Clemens, A. Follenzi, and M. A. Zern
Role of MAPK Phosphatase-1 in Sustained Activation of JNK during Ethanol-induced Apoptosis in Hepatocyte-like VL-17A Cells
J. Biol. Chem., November 2, 2007; 282(44): 31900 - 31908.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
D. Zhang, V. Anantharam, A. Kanthasamy, and A. G. Kanthasamy
Neuroprotective Effect of Protein Kinase C{delta} Inhibitor Rottlerin in Cell Culture and Animal Models of Parkinson's Disease
J. Pharmacol. Exp. Ther., September 1, 2007; 322(3): 913 - 922.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2006