 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
Previous Article | Next Article
The Journal of Neuroscience, March 1, 1998, 18(5):1713-1724
Role of the Jun Kinase Pathway in the Regulation of c-Jun Expression and Apoptosis in Sympathetic Neurons
Andreas Eilers1, Jonathan Whitfield1, Carol Babij1, Lee L. Rubin2, and Jonathan Ham1 1 Eisai London Research Laboratories, University College London, London WC1E 6BT, United Kingdom, and 2 Ontogeny Inc., Cambridge, Massachusetts 02139
When deprived of nerve growth factor (NGF), developing sympathetic neurons die by apoptosis. This death is associated with an increase in the level of c-Jun protein and is blocked by expression of a c-Jun dominant negative mutant. Here we have investigated whether NGF withdrawal activates Jun kinases, a family of stress-activated protein kinases that can stimulate the transcriptional activity of c-Jun by phosphorylating serines 63 and 73 in the transactivation domain and which can activate c-jun gene expression. We found that sympathetic neurons contained high basal levels of Jun kinase activity that increased further after NGF deprivation. In contrast, p38 kinase, another stress-activated protein kinase that can also stimulate c-jun gene expression, was not activated after NGF withdrawal. Consistent with Jun kinase activation, we found using a phospho-c-Jun-specific antibody that c-Jun was phosphorylated on serine 63 after NGF withdrawal. Furthermore, expression of a constitutively active form of MEK kinase 1 (MEKK1), which strongly activates the Jun kinase pathway, increased c-Jun protein levels and c-Jun phosphorylation and induced apoptosis in the presence of NGF. This death could be prevented by co-expression of SEKAL, a dominant negative mutant of SAPK/ERK kinase 1 (SEK1), an activator of Jun kinase that is a target of MEKK1. In contrast, expression of SEKAL alone did not prevent c-Jun expression, increases in c-Jun phosphorylation, or cell death after NGF withdrawal. Thus, activation of Jun kinase and increases in c-Jun phosphorylation and c-Jun protein levels occur at the same time after NGF withdrawal, but c-Jun levels and phosphorylation are regulated by an SEK1-independent pathway.
Key words: apoptosis; c-Jun; Jun kinase; p38 kinase; signal transduction; sympathetic neurons; stress-activated protein kinases
Copyright © 1998 Society for Neuroscience 0270-6474/98/1851713-12$05.00/0
This article has been cited by other articles:
K.-H. Sun, H.-g. Lee, M. A. Smith, and K. Shah
Direct and Indirect Roles of Cyclin-dependent Kinase 5 as an Upstream Regulator in the c-Jun NH2-Terminal Kinase Cascade: Relevance to Neurotoxic Insults in Alzheimer's Disease
Mol. Biol. Cell, November 1, 2009; 20(21): 4611 - 4619.
[Abstract] [Full Text] [PDF]
Z. Yuan, S. Gong, J. Luo, Z. Zheng, B. Song, S. Ma, J. Guo, C. Hu, G. Thiel, C. Vinson, et al.
Opposing Roles for ATF2 and c-Fos in c-Jun-Mediated Neuronal Apoptosis
Mol. Cell. Biol., May 1, 2009; 29(9): 2431 - 2442.
[Abstract] [Full Text] [PDF]
E. Towers, J. Gilley, R. Randall, R. Hughes, M. Kristiansen, and J. Ham
The proapoptotic dp5 gene is a direct target of the MLK-JNK-c-Jun pathway in sympathetic neurons
Nucleic Acids Res., May 1, 2009; 37(9): 3044 - 3060.
[Abstract] [Full Text] [PDF]
B. Bjorkblom, J. C. Vainio, V. Hongisto, T. Herdegen, M. J. Courtney, and E. T. Coffey
All JNKs Can Kill, but Nuclear Localization Is Critical for Neuronal Death
J. Biol. Chem., July 11, 2008; 283(28): 19704 - 19713.
[Abstract] [Full Text] [PDF]
N. Askari, R. Diskin, M. Avitzour, R. Capone, O. Livnah, and D. Engelberg
Hyperactive Variants of p38{alpha} Induce, whereas Hyperactive Variants of p38{gamma} Suppress, Activating Protein 1-mediated Transcription
J. Biol. Chem., January 5, 2007; 282(1): 91 - 99.
[Abstract] [Full Text] [PDF]
L. Xie, R. S. Johnson, and R. S. Freeman
Inhibition of NGF deprivation-induced death by low oxygen involves suppression of BIMEL and activation of HIF-1
J. Cell Biol., March 14, 2005; 168(6): 911 - 920.
[Abstract] [Full Text] [PDF]
G. S. Walsh, N. Orike, D. R. Kaplan, and F. D. Miller
The Invulnerability of Adult Neurons: A Critical Role for p73
J. Neurosci., October 27, 2004; 24(43): 9638 - 9647.
[Abstract] [Full Text] [PDF]
A. F. Lee, D. K. Ho, P. Zanassi, G. S. Walsh, D. R. Kaplan, and F. D. Miller
Evidence That {Delta}Np73 Promotes Neuronal Survival by p53-Dependent and p53-Independent Mechanisms
J. Neurosci., October 13, 2004; 24(41): 9174 - 9184.
[Abstract] [Full Text] [PDF]
J. Cao, M. M. Semenova, V. T. Solovyan, J. Han, E. T. Coffey, and M. J. Courtney
Distinct Requirements for p38{alpha} and c-Jun N-terminal Kinase Stress-activated Protein Kinases in Different Forms of Apoptotic Neuronal Death
J. Biol. Chem., August 20, 2004; 279(34): 35903 - 35913.
[Abstract] [Full Text] [PDF]
L.-Y. Yu, E. Jokitalo, Y.-F. Sun, P. Mehlen, D. Lindholm, M. Saarma, and U. Arumae
GDNF-deprived sympathetic neurons die via a novel nonmitochondrial pathway
J. Cell Biol., December 8, 2003; 163(5): 987 - 997.
[Abstract] [Full Text] [PDF]
P. Giuliano, T. de Cristofaro, A. Affaitati, G. M. Pizzulo, A. Feliciello, C. Criscuolo, G. De Michele, A. Filla, E. V. Avvedimento, and S. Varrone
DNA damage induced by polyglutamine-expanded proteins
Hum. Mol. Genet., September 15, 2003; 12(18): 2301 - 2309.
[Abstract] [Full Text] [PDF]
J. Gilley, P. J. Coffer, and J. Ham
FOXO transcription factors directly activate bim gene expression and promote apoptosis in sympathetic neurons
J. Cell Biol., August 18, 2003; 162(4): 613 - 622.
[Abstract] [Full Text] [PDF]
S. Nakagomi, Y. Suzuki, K. Namikawa, S. Kiryu-Seo, and H. Kiyama
Expression of the Activating Transcription Factor 3 Prevents c-Jun N-Terminal Kinase-Induced Neuronal Death by Promoting Heat Shock Protein 27 Expression and Akt Activation
J. Neurosci., June 15, 2003; 23(12): 5187 - 5196.
[Abstract] [Full Text] [PDF]
S. Yamagishi, M. Yamada, H. Koshimizu, S. Takai, H. Hatanaka, K. Takeda, H. Ichijo, K. Shimoke, and T. Ikeuchi
Apoptosis-Signal Regulating Kinase-1 Is Involved in the Low Potassium-Induced Activation of p38 Mitogen-Activated Protein Kinase and c-Jun in Cultured Cerebellar Granule Neurons
J. Biochem., June 1, 2003; 133(6): 719 - 724.
[Abstract] [Full Text] [PDF]
S. Dziennis and B. A. Habecker
Cytokine Suppression of Dopamine-beta -hydroxylase by Extracellular Signal-regulated Kinase-dependent and -independent Pathways
J. Biol. Chem., April 25, 2003; 278(18): 15897 - 15904.
[Abstract] [Full Text] [PDF]
J.-A. Haefliger, T. Tawadros, L. Meylan, S. L. Gurun, M.-E. Roehrich, D. Martin, B. Thorens, and G. Waeber
The scaffold protein IB1/JIP-1 is a critical mediator of cytokine-induced apoptosis in pancreatic {beta} cells
J. Cell Sci., April 15, 2003; 116(8): 1463 - 1469.
[Abstract] [Full Text] [PDF]
K. Lei and R. J. Davis
JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis
PNAS, March 4, 2003; 100(5): 2432 - 2437.
[Abstract] [Full Text] [PDF]
D. A. Linseman, R. A. Phelps, R. J. Bouchard, S. S. Le, T. A. Laessig, M. L. McClure, and K. A. Heidenreich
Insulin-Like Growth Factor-I Blocks Bcl-2 Interacting Mediator of Cell Death (Bim) Induction and Intrinsic Death Signaling in Cerebellar Granule Neurons
J. Neurosci., November 1, 2002; 22(21): 9287 - 9297.
[Abstract] [Full Text] [PDF]
X. Deng, S. Jayanthi, B. Ladenheim, I. N. Krasnova, and J. L. Cadet
Mice with Partial Deficiency of c-Jun Show Attenuation of Methamphetamine-Induced Neuronal Apoptosis
Mol. Pharmacol., November 1, 2002; 62(5): 993 - 1000.
[Abstract] [Full Text] [PDF]
M. H. Ghahremani, E. Keramaris, T. Shree, Z. Xia, R. J. Davis, R. Flavell, R. S. Slack, and D. S. Park
Interaction of the c-Jun/JNK Pathway and Cyclin-dependent Kinases in Death of Embryonic Cortical Neurons Evoked by DNA Damage
J. Biol. Chem., September 13, 2002; 277(38): 35586 - 35596.
[Abstract] [Full Text] [PDF]
H. Okazawa and S. Estus
The JNK/c-Jun cascade and Alzheimer's disease
American Journal of Alzheimer's Disease and Other Dementias, March 1, 2002; 17(2): 79 - 88.
[Abstract] [PDF]
C. A. Harris, M. Deshmukh, B. Tsui-Pierchala, A. C. Maroney, and E. M. Johnson Jr
Inhibition of the c-Jun N-Terminal Kinase Signaling Pathway by the Mixed Lineage Kinase Inhibitor CEP-1347 (KT7515) Preserves Metabolism and Growth of Trophic Factor-Deprived Neurons
J. Neurosci., January 1, 2002; 22(1): 103 - 113.
[Abstract] [Full Text] [PDF]
A. W. Harrington, J. Y. Kim, and S. O. Yoon
Activation of Rac GTPase by p75 Is Necessary for c-jun N-Terminal Kinase-Mediated Apoptosis
J. Neurosci., January 1, 2002; 22(1): 156 - 166.
[Abstract] [Full Text] [PDF]
S. Le, T. J. Connors, and A. C. Maroney
c-Jun N-terminal Kinase Specifically Phosphorylates p66ShcA at Serine 36 in Response to Ultraviolet Irradiation
J. Biol. Chem., December 14, 2001; 276(51): 48332 - 48336.
[Abstract] [Full Text] [PDF]
D. B. Parkinson, Z. Dong, H. Bunting, J. Whitfield, C. Meier, H. Marie, R. Mirsky, and K. R. Jessen
Transforming Growth Factor beta (TGFbeta ) Mediates Schwann Cell Death In Vitro and In Vivo: Examination of c-Jun Activation, Interactions with Survival Signals, and the Relationship of TGFbeta -Mediated Death to Schwann Cell Differentiation
J. Neurosci., November 1, 2001; 21(21): 8572 - 8585.
[Abstract] [Full Text] [PDF]
S. J. Crocker, W. R. Lamba, P. D. Smith, S. M. Callaghan, R. S. Slack, H. Anisman, and D. S. Park
c-Jun mediates axotomy-induced dopamine neuron death in vivo
PNAS, October 25, 2001; (2001) 231177098.
[Abstract] [Full Text] [PDF]
D. A. Linseman, T. Laessig, M. K. Meintzer, M. McClure, H. Barth, K. Aktories, and K. A. Heidenreich
An Essential Role for Rac/Cdc42 GTPases in Cerebellar Granule Neuron Survival
J. Biol. Chem., October 12, 2001; 276(42): 39123 - 39131.
[Abstract] [Full Text] [PDF]
Y. Levkovitz and J. M. Baraban
A Dominant Negative Inhibitor of the Egr Family of Transcription Regulatory Factors Suppresses Cerebellar Granule Cell Apoptosis by Blocking c-Jun Activation
J. Neurosci., August 15, 2001; 21(16): 5893 - 5901.
[Abstract] [Full Text] [PDF]
Z. Xu, A. C. Maroney, P. Dobrzanski, N. V. Kukekov, and L. A. Greene
The MLK Family Mediates c-Jun N-Terminal Kinase Activation in Neuronal Apoptosis
Mol. Cell. Biol., July 15, 2001; 21(14): 4713 - 4724.
[Abstract] [Full Text] [PDF]
M. Mota, M. Reeder, J. Chernoff, and C. E. Bazenet
Evidence for a Role of Mixed Lineage Kinases in Neuronal Apoptosis
J. Neurosci., July 15, 2001; 21(14): 4949 - 4957.
[Abstract] [Full Text] [PDF]
E. J. Morris, E. Keramaris, H. J. Rideout, R. S. Slack, N. J. Dyson, L. Stefanis, and D. S. Park
Cyclin-Dependent Kinases and P53 Pathways Are Activated Independently and Mediate Bax Activation in Neurons after DNA Damage
J. Neurosci., July 15, 2001; 21(14): 5017 - 5026.
[Abstract] [Full Text] [PDF]
G. S. De Zutter and R. J. Davis
Pro-apoptotic gene expression mediated by the p38 mitogen-activated protein kinase signal transduction pathway
PNAS, May 3, 2001; (2001) 111027698.
[Abstract] [Full Text]
D. Sampath and W. Plunkett
The Role of c-jun Kinase in the Apoptotic Response to Nucleoside Analogue-induced DNA Damage
Cancer Res., November 1, 2000; 60(22): 6408 - 6415.
[Abstract] [Full Text]
E. T. Coffey, V. Hongisto, M. Dickens, R. J. Davis, and M. J. Courtney
Dual Roles for c-Jun N-Terminal Kinase in Developmental and Stress Responses in Cerebellar Granule Neurons
J. Neurosci., October 15, 2000; 20(20): 7602 - 7613.
[Abstract] [Full Text] [PDF]
U. Namgung and Z. Xia
Arsenite-Induced Apoptosis in Cortical Neurons Is Mediated by c-Jun N-Terminal Protein Kinase 3 and p38 Mitogen-Activated Protein Kinase
J. Neurosci., September 1, 2000; 20(17): 6442 - 6451.
[Abstract] [Full Text] [PDF]
G. C. Fletcher, L. Xue, S. K. Passingham, and A. M. Tolkovsky
Death Commitment Point Is Advanced by Axotomy in Sympathetic Neurons
J. Cell Biol., August 21, 2000; 150(4): 741 - 754.
[Abstract] [Full Text] [PDF]
M. Takeda, H. Kato, A. Takamiya, A. Yoshida, and H. Kiyama
Injury-Specific Expression of Activating Transcription Factor-3 in Retinal Ganglion Cells and Its Colocalized Expression with Phosphorylated c-Jun
Invest. Ophthalmol. Vis. Sci., August 1, 2000; 41(9): 2412 - 2421.
[Abstract] [Full Text]
S. I. Savitz and J. A. Kessler
Leukemia Inhibitory Factor Requires Concurrent p75LNTR Signaling to Induce Apoptosis of Cultured Sympathetic Neurons
J. Neurosci., June 1, 2000; 20(11): 4198 - 4205.
[Abstract] [Full Text] [PDF]
M. Matsuoka, B. Wispriyono, Y. Iryo, and H. Igisu
Mercury Chloride Activates c-Jun N-Terminal Kinase and Induces c-jun Expression in LLC-PK1 Cells
Toxicol. Sci., February 1, 2000; 53(2): 361 - 368.
[Abstract] [Full Text] [PDF]
T. Kanamoto, M. Mota, K. Takeda, L. L. Rubin, K. Miyazono, H. Ichijo, and C. E. Bazenet
Role of Apoptosis Signal-Regulating Kinase in Regulation of the c-Jun N-Terminal Kinase Pathway and Apoptosis in Sympathetic Neurons
Mol. Cell. Biol., January 1, 2000; 20(1): 196 - 204.
[Abstract] [Full Text]
D. L. Clemm, L. Sherman, V. Boonyaratanakornkit, W. T. Schrader, N. L. Weigel, and D. P. Edwards
Differential Hormone-Dependent Phosphorylation of Progesterone Receptor A and B Forms Revealed by a Phosphoserine Site-Specific Monoclonal Antibody
Mol. Endocrinol., January 1, 2000; 14(1): 52 - 65.
[Abstract] [Full Text]
I. E. Mazzoni, F. A. Said, R. Aloyz, F. D. Miller, and D. Kaplan
Ras Regulates Sympathetic Neuron Survival by Suppressing the p53-Mediated Cell Death Pathway
J. Neurosci., November 15, 1999; 19(22): 9716 - 9727.
[Abstract] [Full Text] [PDF]
Y. Satomi, S. Miyamoto, and M. N. Gould
Induction of AP-1 activity by perillyl alcohol in breast cancer cells
Carcinogenesis, October 1, 1999; 20(10): 1957 - 1961.
[Abstract] [Full Text] [PDF]
H. Hida, S. Nagano, M. Takeda, and B. Soliven
Regulation of Mitogen-Activated Protein Kinases by Sphingolipid Products in Oligodendrocytes
J. Neurosci., September 1, 1999; 19(17): 7458 - 7467.
[Abstract] [Full Text] [PDF]
Y. Luo, A. Hattori, J. Munoz, Z.-H. Qin, and G. S. Roth
Intrastriatal Dopamine Injection Induces Apoptosis Through Oxidation-Involved Activation of Transcription Factors AP-1 and NF-kappa B in Rats
Mol. Pharmacol., August 1, 1999; 56(2): 254 - 264.
[Abstract] [Full Text]
A. Martin-Villalba, I. Herr, I. Jeremias, M. Hahne, R. Brandt, J. Vogel, J. Schenkel, T. Herdegen, and K.-M. Debatin
CD95 Ligand (Fas-L/APO-1L) and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Mediate Ischemia-Induced Apoptosis in Neurons
J. Neurosci., May 15, 1999; 19(10): 3809 - 3817.
[Abstract] [Full Text] [PDF]
T. Herdegen, K. Mielke, and T. Kallunki
Review : c-Jun and the c-Jun Amino-Terminal Kinases: Bipotential Components of the Neuronal Stress Response
Neuroscientist, May 1, 1999; 5(3): 147 - 154.
[Abstract] [PDF]
J. Y. H. Kim, M. E. Sutton, D. J. Lu, T. A. Cho, L. C. Goumnerova, L. Goritchenko, J. R. Kaufman, K. K. Lam, A. L. Billet, N. J. Tarbell, et al.
Activation of Neurotrophin-3 Receptor TrkC Induces Apoptosis in Medulloblastomas
Cancer Res., February 1, 1999; 59(3): 711 - 719.
[Abstract] [Full Text] [PDF]
C. N. G. Anderson and A. M. Tolkovsky
A Role for MAPK/ERK in Sympathetic Neuron Survival: Protection against a p53-Dependent, JNK-Independent Induction of Apoptosis by Cytosine Arabinoside
J. Neurosci., January 15, 1999; 19(2): 664 - 673.
[Abstract] [Full Text] [PDF]
C Sanz, Y Leon, S Canon, L Alvarez, F Giraldez, and I Varela-Nieto
Pattern of expression of the jun family of transcription factors during the early development of the inner ear: implications in apoptosis
J. Cell Sci., January 11, 1999; 112(22): 3967 - 3974.
[Abstract] [PDF]
S. B. Maggirwar, P. D. Sarmiere, S. Dewhurst, and R. S. Freeman
Nerve Growth Factor-Dependent Activation of NF-kappa B Contributes to Survival of Sympathetic Neurons
J. Neurosci., December 15, 1998; 18(24): 10356 - 10365.
[Abstract] [Full Text] [PDF]
R. S. Aloyz, S. X. Bamji, C. D. Pozniak, J. G. Toma, J. Atwal, D. R. Kaplan, and F. D. Miller
P53 Is Essential for Developmental Neuron Death as Regulated by the TrkA and p75 Neurotrophin Receptors
J. Cell Biol., December 14, 1998; 143(6): 1691 - 1703.
[Abstract] [Full Text] [PDF]
T. Herdegen, F.-X. Claret, T. Kallunki, A. Martin-Villalba, C. Winter, T. Hunter, and M. Karin
Lasting N-Terminal Phosphorylation of c-Jun and Activation of c-Jun N-Terminal Kinases after Neuronal Injury
J. Neurosci., July 15, 1998; 18(14): 5124 - 5135.
[Abstract] [Full Text] [PDF]
Y. F. Liu, D. Dorow, and J. Marshall
Activation of MLK2-mediated Signaling Cascades by Polyglutamine-expanded Huntingtin
J. Biol. Chem., June 16, 2000; 275(25): 19035 - 19040.
[Abstract] [Full Text] [PDF]
T. C. Harding, L. Xue, A. Bienemann, D. Haywood, M. Dickens, A. M. Tolkovsky, and J. B. Uney
Inhibition of JNK by Overexpression of the JNK Binding Domain of JIP-1 Prevents Apoptosis in Sympathetic Neurons
J. Biol. Chem., February 9, 2001; 276(7): 4531 - 4534.
[Abstract] [Full Text] [PDF]
R. J. Crowder and R. S. Freeman
Glycogen Synthase Kinase-3beta Activity Is Critical for Neuronal Death Caused by Inhibiting Phosphatidylinositol 3-Kinase or Akt but Not for Death Caused by Nerve Growth Factor Withdrawal
J. Biol. Chem., October 27, 2000; 275(44): 34266 - 34271.
[Abstract] [Full Text] [PDF]
S. Yamagishi, M. Yamada, Y. Ishikawa, T. Matsumoto, T. Ikeuchi, and H. Hatanaka
p38 Mitogen-activated Protein Kinase Regulates Low Potassium-induced c-Jun Phosphorylation and Apoptosis in Cultured Cerebellar Granule Neurons
J. Biol. Chem., February 9, 2001; 276(7): 5129 - 5133.
[Abstract] [Full Text] [PDF]
A. C. Maroney, J. P. Finn, T. J. Connors, J. T. Durkin, T. Angeles, G. Gessner, Z. Xu, S. L. Meyer, M. J. Savage, L. A. Greene, et al.
CEP-1347 (KT7515), a Semisynthetic Inhibitor of the Mixed Lineage Kinase Family
J. Biol. Chem., June 29, 2001; 276(27): 25302 - 25308.
[Abstract] [Full Text] [PDF]
D. Daily, A. Vlamis-Gardikas, D. Offen, L. Mittelman, E. Melamed, A. Holmgren, and A. Barzilai
Glutaredoxin Protects Cerebellar Granule Neurons from Dopamine-induced Apoptosis by Dual Activation of the Ras-Phosphoinositide 3-Kinase and Jun N-terminal Kinase Pathways
J. Biol. Chem., June 8, 2001; 276(24): 21618 - 21626.
[Abstract] [Full Text] [PDF]
G. S. De Zutter and R. J. Davis
Pro-apoptotic gene expression mediated by the p38 mitogen-activated protein kinase signal transduction pathway
PNAS, May 22, 2001; 98(11): 6168 - 6173.
[Abstract] [Full Text] [PDF]
S. J. Crocker, W. R. Lamba, P. D. Smith, S. M. Callaghan, R. S. Slack, H. Anisman, and D. S. Park
c-Jun mediates axotomy-induced dopamine neuron death in vivo
PNAS, November 6, 2001; 98(23): 13385 - 13390.
[Abstract] [Full Text] [PDF]
J.-D. Delcroix, S. Averill, K. Fernandes, D. R. Tomlinson, J. V. Priestley, and P. Fernyhough
Axonal Transport of Activating Transcription Factor-2 Is Modulated by Nerve Growth Factor in Nociceptive Neurons
J. Neurosci., September 15, 1999; 19(18): RC24 - RC24.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|