 |
||||
|
||||
|
||||
|
||||
Previous Article | Next Article
The Journal of Neuroscience, January 1, 2002, 22(1):156-166
Activation of Rac GTPase by p75 Is Necessary for c-jun N-Terminal Kinase-Mediated Apoptosis
Anthony W. Harrington1, 2, Ju Young Kim1, 3, and Sung Ok Yoon1 1 Neurobiotech Center and Department of Neuroscience, 2 Biochemistry Program, and 3 Molecular, Cellular, and Developmental Biology Program, Ohio State University, Columbus, Ohio 43210
The neurotrophin receptor p75 can induce apoptosis both in vitro and in vivo. The mechanisms by which p75 induces apoptosis have remained mostly unknown. Here, we report that p75 activates Rac GTPase, which in turn activates c-jun N-terminal kinase (JNK), including an injury-specific JNK3, in an NGF-dependent manner. N17Rac blocks this JNK activation and subsequent NGF-dependent apoptosis, indicating that activation of Rac GTPase is required for JNK activation and apoptosis induced by p75. In addition, p75-mediated Rac activation is modulated by coactivation of Trk, identifying Rac GTPase as one of the key molecules whose activity is critical for cell survival and death in neurotrophin signaling. The crucial role of the JNK pathway in p75 signaling is further confirmed by the results that blocking p75 from signaling via the JNK pathway or suppressing the JNK activity itself led to inhibition of NGF-dependent death. Together, these results indicate that the apoptotic machinery of p75 comprises Rac GTPase and JNK.
Key words: apoptosis; Rac GTPase; c-jun N-terminal kinase; signal transduction; p75; NGF
Copyright © 2002 Society for Neuroscience 0270-6474/02/221156-11$05.00/0
This article has been cited by other articles:
M. Volosin, C. Trotter, A. Cragnolini, R. S. Kenchappa, M. Light, B. L. Hempstead, B. D. Carter, and W. J. Friedman
Induction of Proneurotrophins and Activation of p75NTR-Mediated Apoptosis via Neurotrophin Receptor-Interacting Factor in Hippocampal Neurons after Seizures
J. Neurosci., September 24, 2008; 28(39): 9870 - 9879.
[Abstract] [Full Text] [PDF]
A. Caporali, E. Pani, A. J.G. Horrevoets, N. Kraenkel, A. Oikawa, G. B. Sala-Newby, M. Meloni, B. Cristofaro, G. Graiani, A. S. Leroyer, et al.
Neurotrophin p75 Receptor (p75NTR) Promotes Endothelial Cell Apoptosis and Inhibits Angiogenesis: Implications for Diabetes-Induced Impaired Neovascularization in Ischemic Limb Muscles
Circ. Res., July 18, 2008; 103(2): e15 - e26.
[Abstract] [Full Text] [PDF]
E. J. Coulson, L. M. May, S. L. Osborne, K. Reid, C. K. Underwood, F. A. Meunier, P. F. Bartlett, and P. Sah
p75 Neurotrophin Receptor Mediates Neuronal Cell Death by Activating GIRK Channels through Phosphatidylinositol 4,5-Bisphosphate
J. Neurosci., January 2, 2008; 28(1): 315 - 324.
[Abstract] [Full Text] [PDF]
Q. M. Li, C. Tep, T. Y. Yune, X. Z. Zhou, T. Uchida, K. P. Lu, and S. O. Yoon
Opposite Regulation of Oligodendrocyte Apoptosis by JNK3 and Pin1 after Spinal Cord Injury
J. Neurosci., August 1, 2007; 27(31): 8395 - 8404.
[Abstract] [Full Text] [PDF]
A. G. Miraglia, S. Travaglione, S. Meschini, L. Falzano, P. Matarrese, M. G. Quaranta, M. Viora, C. Fiorentini, and A. Fabbri
Cytotoxic Necrotizing Factor 1 Prevents Apoptosis via the Akt/I{kappa}B Kinase Pathway: Role of Nuclear Factor-{kappa}B and Bcl-2
Mol. Biol. Cell, July 1, 2007; 18(7): 2735 - 2744.
[Abstract] [Full Text] [PDF]
S. Jin, R. M. Ray, and L. R. Johnson
Rac1 mediates intestinal epithelial cell apoptosis via JNK
Am J Physiol Gastrointest Liver Physiol, December 1, 2006; 291(6): G1137 - G1147.
[Abstract] [Full Text] [PDF]
K. Obata, H. Katsura, J. Sakurai, K. Kobayashi, H. Yamanaka, Y. Dai, T. Fukuoka, and K. Noguchi
Suppression of the p75 Neurotrophin Receptor in Uninjured Sensory Neurons Reduces Neuropathic Pain after Nerve Injury.
J. Neurosci., November 15, 2006; 26(46): 11974 - 11986.
[Abstract] [Full Text] [PDF]
J. Tan and R. K. Shepherd
Aminoglycoside-Induced Degeneration of Adult Spiral Ganglion Neurons Involves Differential Modulation of Tyrosine Kinase B and p75 Neurotrophin Receptor Signaling
Am. J. Pathol., August 1, 2006; 169(2): 528 - 543.
[Abstract] [Full Text] [PDF]
S. M. Massa, Y. Xie, T. Yang, A. W. Harrington, M. L. Kim, S. O. Yoon, R. Kraemer, L. A. Moore, B. L. Hempstead, and F. M. Longo
Small, nonpeptide p75NTR ligands induce survival signaling and inhibit proNGF-induced death.
J. Neurosci., May 17, 2006; 26(20): 5288 - 5300.
[Abstract] [Full Text] [PDF]
M. A. Belmonte, M. F. Santos, A. H. Kihara, C. Y. I. Yan, and D. E. Hamassaki
Light-Induced Photoreceptor Degeneration in the Mouse Involves Activation of the Small GTPase Rac1.
Invest. Ophthalmol. Vis. Sci., March 1, 2006; 47(3): 1193 - 1200.
[Abstract] [Full Text] [PDF]
E. S. Jeon, H. Y. Song, M. R. Kim, H. J. Moon, Y. C. Bae, J. S. Jung, and J. H. Kim
Sphingosylphosphorylcholine induces proliferation of human adipose tissue-derived mesenchymal stem cells via activation of JNK
J. Lipid Res., March 1, 2006; 47(3): 653 - 664.
[Abstract] [Full Text] [PDF]
J. C. He, I. Gomes, T. Nguyen, G. Jayaram, P. T. Ram, L. A. Devi, and R. Iyengar
The G{alpha}o/i-coupled Cannabinoid Receptor-mediated Neurite Outgrowth Involves Rap Regulation of Src and Stat3
J. Biol. Chem., September 30, 2005; 280(39): 33426 - 33434.
[Abstract] [Full Text] [PDF]
M. S. Linggi, T. L. Burke, B. B. Williams, A. Harrington, R. Kraemer, B. L. Hempstead, S. O. Yoon, and B. D. Carter
Neurotrophin Receptor Interacting Factor (NRIF) Is an Essential Mediator of Apoptotic Signaling by the p75 Neurotrophin Receptor
J. Biol. Chem., April 8, 2005; 280(14): 13801 - 13808.
[Abstract] [Full Text] [PDF]
K. Kanekura, Y. Hashimoto, Y. Kita, J. Sasabe, S. Aiso, I. Nishimoto, and M. Matsuoka
A Rac1/Phosphatidylinositol 3-Kinase/Akt3 Anti-apoptotic Pathway, Triggered by AlsinLF, the Product of the ALS2 Gene, Antagonizes Cu/Zn-superoxide Dismutase (SOD1) Mutant-induced Motoneuronal Cell Death
J. Biol. Chem., February 11, 2005; 280(6): 4532 - 4543.
[Abstract] [Full Text] [PDF]
E. C. Yeiser, N. J. Rutkoski, A. Naito, J.-i. Inoue, and B. D. Carter
Neurotrophin Signaling through the p75 Receptor Is Deficient in traf6-/- Mice
J. Neurosci., November 17, 2004; 24(46): 10521 - 10529.
[Abstract] [Full Text] [PDF]
E. B. E. Becker, J. Howell, Y. Kodama, P. A. Barker, and A. Bonni
Characterization of the c-Jun N-Terminal Kinase-BimEL Signaling Pathway in Neuronal Apoptosis
J. Neurosci., October 6, 2004; 24(40): 8762 - 8770.
[Abstract] [Full Text] [PDF]
C. Bandtlow and G. Dechant
From Cell Death to Neuronal Regeneration, Effects of the p75 Neurotrophin Receptor Depend on Interactions with Partner Subunits
Sci. Signal., June 1, 2004; 2004(235): pe24 - pe24.
[Abstract] [Full Text] [PDF]
J. J. Gentry, N. J. Rutkoski, T. L. Burke, and B. D. Carter
A Functional Interaction between the p75 Neurotrophin Receptor Interacting Factors, TRAF6 and NRIF
J. Biol. Chem., April 16, 2004; 279(16): 16646 - 16656.
[Abstract] [Full Text] [PDF]
C. E. Paul, E. Vereker, K. M. Dickson, and P. A. Barker
A Pro-Apoptotic Fragment of the p75 Neurotrophin Receptor Is Expressed in p75NTRExonIV Null Mice
J. Neurosci., February 25, 2004; 24(8): 1917 - 1923.
[Abstract] [Full Text] [PDF]
A. L. Bhakar, J. L. Howell, C. E. Paul, A. H. Salehi, E. B. E. Becker, F. Said, A. Bonni, and P. A. Barker
Apoptosis Induced by p75NTR Overexpression Requires Jun Kinase-Dependent Phosphorylation of Bad
J. Neurosci., December 10, 2003; 23(36): 11373 - 11381.
[Abstract] [Full Text] [PDF]
B. Zhang, Y. Zhang, and E. Shacter
Caspase 3-Mediated Inactivation of Rac GTPases Promotes Drug-Induced Apoptosis in Human Lymphoma Cells
Mol. Cell. Biol., August 15, 2003; 23(16): 5716 - 5725.
[Abstract] [Full Text] [PDF]
J. Y. Kim, Q. Sun, M. Oglesbee, and S. O. Yoon
The Role of ErbB2 Signaling in the Onset of Terminal Differentiation of Oligodendrocytes In Vivo
J. Neurosci., July 2, 2003; 23(13): 5561 - 5571.
[Abstract] [Full Text] [PDF]
A. Middlemas, J.-D. Delcroix, N. M. Sayers, D. R. Tomlinson, and P. Fernyhough
Enhanced activation of axonally transported stress-activated protein kinases in peripheral nerve in diabetic neuropathy is prevented by neurotrophin-3
Brain, July 1, 2003; 126(7): 1671 - 1682.
[Abstract] [Full Text] [PDF]
W. Tan, S. Rouen, K. M. Barkus, Y. S. Dremina, D. Hui, J. A. Christianson, D. E. Wright, S. O. Yoon, and R. T. Dobrowsky
Nerve Growth Factor Blocks the Glucose-induced Down-regulation of Caveolin-1 Expression in Schwann Cells via p75 Neurotrophin Receptor Signaling
J. Biol. Chem., June 13, 2003; 278(25): 23151 - 23162.
[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]
V. Waetzig and T. Herdegen
A Single c-Jun N-terminal Kinase Isoform (JNK3-p54) Is an Effector in Both Neuronal Differentiation and Cell Death
J. Biol. Chem., January 3, 2003; 278(1): 567 - 572.
[Abstract] [Full Text] [PDF]
A. H. Salehi, S. Xanthoudakis, and P. A. Barker
NRAGE, a p75 Neurotrophin Receptor-interacting Protein, Induces Caspase Activation and Cell Death through a JNK-dependent Mitochondrial Pathway
J. Biol. Chem., December 6, 2002; 277(50): 48043 - 48050.
[Abstract] [Full Text] [PDF]
C. Yan, Y. Liang, K. D. Nylander, and N. F. Schor
TrkA as a Life and Death Receptor: Receptor Dose as a Mediator of Function
Cancer Res., September 1, 2002; 62(17): 4867 - 4875.
[Abstract] [Full Text] [PDF]
M. Palmada, S. Kanwal, N.J. Rutkoski, C. Gustafson-Brown, R.S. Johnson, R. Wisdom, and B.D. Carter
c-jun is essential for sympathetic neuronal death induced by NGF withdrawal but not by p75 activation
J. Cell Biol., August 5, 2002; 158(3): 453 - 461.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|