 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
Previous Article | Next Article
The Journal of Neuroscience, January 15, 2001, 21(2):434-443
Differential Regulation of Mitogen-Activated Protein Kinases ERK1/2 and ERK5 by Neurotrophins, Neuronal Activity, and cAMP in Neurons
Jane E. Cavanaugh1, 2, James Ham1, Michal Hetman1, 2, Steve Poser2, Chen Yan3, and Zhengui Xia1, 2 Departments of 1 Environmental Health and 2 Pharmacology, University of Washington, Seattle, Washington 98195-7234, and 3 Cardiology Unit, University of Rochester, Rochester, New York 14642
Activation of the extracellular signal-regulated kinase 1 (ERK1) and ERK2 by neurotrophins, neuronal activity, or cAMP has been strongly implicated in differentiation, survival, and adaptive responses of neurons during development and in the adult brain. Recently, a new member of the mitogen-activated protein (MAP) kinase family, ERK5, was discovered. Like ERK1 and ERK2, ERK5 is expressed in neurons, and ERK5 stimulation by epidermal growth factor is blocked by the MAP kinase/ERK kinase 1 (MEK1) inhibitors PD98059 and U0126. This suggests the interesting possibility that some of the functions attributed to ERK1/2 may be mediated by ERK5. However, the regulatory properties of ERK5 in primary cultured neurons have not been reported. Here we examined the regulation of ERK5 signaling in primary cultured cortical neurons. Our data demonstrate that, similar to ERK1/2, ERK5 is activated by neurotrophins including brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and NT-4. BDNF stimulation of ERK5 required the activity of MEK5. Surprisingly, ERK5 was not stimulated by cAMP or neuronal activity induced by glutamate or membrane depolarization. In contrast to ERK1/2, ERK5 strongly activated the transcriptional activity of myocyte enhancer factor 2C (MEF2C) in pheochromocytoma 12 (PC12) cells and was required for neurotrophin stimulation of MEF2C transcription in both PC12 cells and cortical neurons. Furthermore, ERK1/2, but not ERK5, induced transcription from Elk1 and the cAMP/ Ca2+ response element in PC12 cells. Our data suggest that mechanisms for regulation of ERK5 and downstream transcriptional pathways regulated by ERK5 are distinct from those of ERK1/2 in neurons. Furthermore, ERK5 is the first MAP kinase identified whose activity is stimulated by neurotrophins but not by neuronal activity.
Key words: signal transduction; CNS; cortical neurons; neurons; MAP kinase; ERK1/2; ERK5; BMK1; CREB; CRE; MEF2C; BDNF; glutamate; membrane depolarization; neuronal activity; neurotrophin; cAMP
Copyright © 2001 Society for Neuroscience 0270-6474/01/212434-10$05.00/0
This article has been cited by other articles:
Y. Obara, A. Yamauchi, S. Takehara, W. Nemoto, M. Takahashi, P. J. S. Stork, and N. Nakahata
ERK5 Activity Is Required for Nerve Growth Factor-induced Neurite Outgrowth and Stabilization of Tyrosine Hydroxylase in PC12 Cells
J. Biol. Chem., August 28, 2009; 284(35): 23564 - 23573.
[Abstract] [Full Text] [PDF]
M. Rosario, R. Franke, C. Bednarski, and W. Birchmeier
The neurite outgrowth multiadaptor RhoGAP, NOMA-GAP, regulates neurite extension through SHP2 and Cdc42
J. Cell Biol., July 24, 2007; 178(3): 503 - 516.
[Abstract] [Full Text] [PDF]
K. Cude, Y. Wang, H.-J. Choi, S.-L. Hsuan, H. Zhang, C.-Y. Wang, and Z. Xia
Regulation of the G2-M cell cycle progression by the ERK5-NF{kappa}B signaling pathway
J. Cell Biol., April 23, 2007; 177(2): 253 - 264.
[Abstract] [Full Text] [PDF]
T. Mizushima, K. Obata, H. Katsura, J. Sakurai, K. Kobayashi, H. Yamanaka, Y. Dai, T. Fukuoka, T. Mashimo, and K. Noguchi
Intensity-Dependent Activation of Extracellular Signal-Regulated Protein Kinase 5 in Sensory Neurons Contributes to Pain Hypersensitivity
J. Pharmacol. Exp. Ther., April 1, 2007; 321(1): 28 - 34.
[Abstract] [Full Text] [PDF]
M. Kidd, I. M. Modlin, G. N. Eick, R. L. Camp, and S. M. Mane
Role of CCN2/CTGF in the proliferation of Mastomys enterochromaffin-like cells and gastric carcinoid development
Am J Physiol Gastrointest Liver Physiol, January 1, 2007; 292(1): G191 - G200.
[Abstract] [Full Text] [PDF]
S. Zhuang and R. G. Schnellmann
A Death-Promoting Role for Extracellular Signal-Regulated Kinase
J. Pharmacol. Exp. Ther., December 1, 2006; 319(3): 991 - 997.
[Abstract] [Full Text] [PDF]
Y. Wang, B. Su, and Z. Xia
Brain-derived Neurotrophic Factor Activates ERK5 in Cortical Neurons via a Rap1-MEKK2 Signaling Cascade
J. Biol. Chem., November 24, 2006; 281(47): 35965 - 35974.
[Abstract] [Full Text] [PDF]
K. Kalita, G. Kharebava, J.-J. Zheng, and M. Hetman
Role of Megakaryoblastic Acute Leukemia-1 in ERK1/2-Dependent Stimulation of Serum Response Factor-Driven Transcription by BDNF or Increased Synaptic Activity
J. Neurosci., September 27, 2006; 26(39): 10020 - 10032.
[Abstract] [Full Text] [PDF]
L. Liu, P. Cundiff, G. Abel, Y. Wang, R. Faigle, H. Sakagami, M. Xu, and Z. Xia
Extracellular signal-regulated kinase (ERK) 5 is necessary and sufficient to specify cortical neuronal fate
PNAS, June 20, 2006; 103(25): 9697 - 9702.
[Abstract] [Full Text] [PDF]
X. Lu, L. Gilbert, X. He, J. Rubin, and M. S. Nanes
Transcriptional Regulation of the Osterix (Osx, Sp7) Promoter by Tumor Necrosis Factor Identifies Disparate Effects of Mitogen-activated Protein Kinase and NF{kappa}B Pathways
J. Biol. Chem., March 10, 2006; 281(10): 6297 - 6306.
[Abstract] [Full Text] [PDF]
K. Ishizawa, Y. Izawa, H. Ito, C. Miki, K. Miyata, Y. Fujita, Y. Kanematsu, K. Tsuchiya, T. Tamaki, A. Nishiyama, et al.
Aldosterone Stimulates Vascular Smooth Muscle Cell Proliferation Via Big Mitogen-Activated Protein Kinase 1 Activation
Hypertension, October 1, 2005; 46(4): 1046 - 1052.
[Abstract] [Full Text] [PDF]
M. Alonso, P. Bekinschtein, M. Cammarota, M. R.M. Vianna, I. Izquierdo, and J. H. Medina
Endogenous BDNF is required for long-term memory formation in the rat parietal cortex
Learn. Mem., September 1, 2005; 12(5): 504 - 510.
[Abstract] [Full Text] [PDF]
L.-M. Sturla, C. W. Cowan, L. Guenther, R. C. Castellino, J. Y.H. Kim, and S. L. Pomeroy
A Novel Role for Extracellular Signal-Regulated Kinase 5 and Myocyte Enhancer Factor 2 in Medulloblastoma Cell Death
Cancer Res., July 1, 2005; 65(13): 5683 - 5689.
[Abstract] [Full Text] [PDF]
S. Lesne, C. Gabriel, D. A. Nelson, E. White, E. T. MacKenzie, D. Vivien, and A. Buisson
Akt-dependent Expression of NAIP-1 Protects Neurons against Amyloid-{beta} Toxicity
J. Biol. Chem., July 1, 2005; 280(26): 24941 - 24947.
[Abstract] [Full Text] [PDF]
M. Alonso, J. H. Medina, and L. Pozzo-Miller
ERK1/2 Activation Is Necessary for BDNF to Increase Dendritic Spine Density in Hippocampal CA1 Pyramidal Neurons
Learn. Mem., March 1, 2004; 11(2): 172 - 178.
[Abstract] [Full Text] [PDF]
B.-e Xu, S. Stippec, L. Lenertz, B.-H. Lee, W. Zhang, Y.-K. Lee, and M. H. Cobb
WNK1 Activates ERK5 by an MEKK2/3-dependent Mechanism
J. Biol. Chem., February 27, 2004; 279(9): 7826 - 7831.
[Abstract] [Full Text] [PDF]
G. Q. Butcher, B. Lee, and K. Obrietan
Temporal Regulation of Light-Induced Extracellular Signal-Regulated Kinase Activation in the Suprachiasmatic Nucleus
J Neurophysiol, December 1, 2003; 90(6): 3854 - 3863.
[Abstract] [Full Text] [PDF]
L. Liu, J. E. Cavanaugh, Y. Wang, H. Sakagami, Z. Mao, and Z. Xia
ERK5 activation of MEF2-mediated gene expression plays a critical role in BDNF-promoted survival of developing but not mature cortical neurons
PNAS, July 8, 2003; 100(14): 8532 - 8537.
[Abstract] [Full Text] [PDF]
S. J. Cameron, S. Malik, M. Akaike, N. Lerner-Marmarosh, C. Yan, J.-D. Lee, J.-i. Abe, and J. Yang
Regulation of Epidermal Growth Factor-induced Connexin 43 Gap Junction Communication by Big Mitogen-activated Protein Kinase 1/ERK5 but Not ERK1/2 Kinase Activation
J. Biol. Chem., May 9, 2003; 278(20): 18682 - 18688.
[Abstract] [Full Text] [PDF]
M. Hetman, S.-L. Hsuan, A. Habas, M. J. Higgins, and Z. Xia
ERK1/2 Antagonizes Glycogen Synthase Kinase-3beta -induced Apoptosis in Cortical Neurons
J. Biol. Chem., December 13, 2002; 277(51): 49577 - 49584.
[Abstract] [Full Text] [PDF]
G. W. Pearson and M. H. Cobb
Cell Condition-dependent Regulation of ERK5 by cAMP
J. Biol. Chem., December 6, 2002; 277(50): 48094 - 48098.
[Abstract] [Full Text] [PDF]
S. J. Sohn, B. K. Sarvis, D. Cado, and A. Winoto
ERK5 MAPK Regulates Embryonic Angiogenesis and Acts as a Hypoxia-sensitive Repressor of Vascular Endothelial Growth Factor Expression
J. Biol. Chem., November 1, 2002; 277(45): 43344 - 43351.
[Abstract] [Full Text] [PDF]
M. Buschbeck, J. Eickhoff, M. N. Sommer, and A. Ullrich
Phosphotyrosine-specific Phosphatase PTP-SL Regulates the ERK5 Signaling Pathway
J. Biol. Chem., August 9, 2002; 277(33): 29503 - 29509.
[Abstract] [Full Text] [PDF]
Y. Suzaki, M. Yoshizumi, S. Kagami, A. H. Koyama, Y. Taketani, H. Houchi, K. Tsuchiya, E. Takeda, and T. Tamaki
Hydrogen Peroxide Stimulates c-Src-mediated Big Mitogen-activated Protein Kinase 1 (BMK1) and the MEF2C Signaling Pathway in PC12 Cells. POTENTIAL ROLE IN CELL SURVIVAL FOLLOWING OXIDATIVE INSULTS
J. Biol. Chem., March 8, 2002; 277(11): 9614 - 9621.
[Abstract] [Full Text] [PDF]
M. Stanciu and D. B. DeFranco
Prolonged Nuclear Retention of Activated Extracellular Signal-regulated Protein Kinase Promotes Cell Death Generated by Oxidative Toxicity or Proteasome Inhibition in a Neuronal Cell Line
J. Biol. Chem., February 1, 2002; 277(6): 4010 - 4017.
[Abstract] [Full Text] [PDF]
W. A. Pedersen, R. Wan, P. Zhang, and M. P. Mattson
Urocortin, But Not Urocortin II, Protects Cultured Hippocampal Neurons from Oxidative and Excitotoxic Cell Death via Corticotropin-Releasing Hormone Receptor Type I
J. Neurosci., January 15, 2002; 22(2): 404 - 412.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|