QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, December 10, 2003, 23(36):11373-11381

This Article Full Text Full Text (PDF) Supplementary Figures Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (60) Citing Articles via Google Scholar Google Scholar Articles by Bhakar, A. L. Articles by Barker, P. A. Search for Related Content PubMed PubMed Citation Articles by Bhakar, A. L. Articles by Barker, P. A. Pubmed/NCBI databases Substance via MeSH

 Previous Article  |  Next Article 

Cellular/Molecular
Apoptosis Induced by p75NTR Overexpression Requires Jun Kinase-Dependent Phosphorylation of Bad

Asha L. Bhakar,¹ Jenny L. Howell,¹ Christine E. Paul,¹ Amir H. Salehi,¹ Esther B. E. Becker,² Farid Said,³ Azad Bonni,² and Philip A. Barker¹

¹Centre for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada, H3A 2B4, ²Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, and ³Aegera Therapeutics Inc., Montreal, Quebec, Canada, H3E 1A8

The p75 neurotrophin receptor (p75NTR), a member of the tumor necrosis factor receptor superfamily, facilitates apoptosis during development and after injury to the CNS. The signaling cascades activated by p75NTR that result in apoptosis remain poorly understood. In this study, we show that overexpression of p75NTR in primary cortical neurons, in pheochromocytoma cell line (PC12) cells, and in glioma cells results in activation of Jun kinase (JNK), accumulation of cytochrome c within the cytosol, and activation of caspases 9, 6, and 3. To link p75NTR-dependent JNK activation to mitochondrial cytochrome c release, regulation of BH3-domain-only family members was examined. Transcription of BH3-domain-only family members was not induced by p75NTR, but p75NTR-dependent JNK activation resulted in phosphorylation and oligomerization of the BH3-domain-only family member Bad. Loss of function experiments using Bad dominant negatives or RNA interference demonstrated a requirement for Bad in p75NTR-induced apoptosis. Together, these studies provide the first data linking apoptosis induced by p75NTR to the phosphorylation of BH3-domain-only family members.

Key words: apoptosis; jun kinase; neurotrophin; receptor; trk; cell death

---

Received July 11, 2003; revised October 21, 2003; accepted October 22, 2003.

This article has been cited by other articles:

				A. Caporali and C. Emanueli Cardiovascular Actions of Neurotrophins Physiol Rev, January 1, 2009; 89(1): 279 - 308. [Abstract] [Full Text] [PDF]

				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]

				Q.-L. Fu, B. Hu, W. Wu, R. B. Pepinsky, S. Mi, and K.-F. So Blocking LINGO-1 Function Promotes Retinal Ganglion Cell Survival Following Ocular Hypertension and Optic Nerve Transection Invest. Ophthalmol. Vis. Sci., March 1, 2008; 49(3): 975 - 985. [Abstract] [Full Text] [PDF]

				Y. Kim, P. Zhou, L. Qian, J.-Z. Chuang, J. Lee, C. Li, C. Iadecola, C. Nathan, and A. Ding MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival J. Exp. Med., September 3, 2007; 204(9): 2063 - 2074. [Abstract] [Full Text] [PDF]

				M. Pehar, M. R. Vargas, K. M. Robinson, P. Cassina, P. J. Diaz-Amarilla, T. M. Hagen, R. Radi, L. Barbeito, and J. S. Beckman Mitochondrial Superoxide Production and Nuclear Factor Erythroid 2-Related Factor 2 Activation in p75 Neurotrophin Receptor-Induced Motor Neuron Apoptosis J. Neurosci., July 18, 2007; 27(29): 7777 - 7785. [Abstract] [Full Text] [PDF]

				A. Ramos, W. Chi Ho, S. Forte, K. Dickson, J. Boutilier, K. Favell, and P. A. Barker Hypo-Osmolar Stress Induces p75NTR Expression by Activating Sp1-Dependent Transcription J. Neurosci., February 7, 2007; 27(6): 1498 - 1506. [Abstract] [Full Text] [PDF]

				B. Cai, S. H. Chang, E. B. E. Becker, A. Bonni, and Z. Xia p38 MAP Kinase Mediates Apoptosis through Phosphorylation of BimEL at Ser-65 J. Biol. Chem., September 1, 2006; 281(35): 25215 - 25222. [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]

				M. Volosin, W. Song, R. D. Almeida, D. R. Kaplan, B. L. Hempstead, and W. J. Friedman Interaction of survival and death signaling in basal forebrain neurons: roles of neurotrophins and proneurotrophins. J. Neurosci., July 19, 2006; 26(29): 7756 - 7766. [Abstract] [Full Text] [PDF]

				H. K. Wong, M. Fricker, A. Wyttenbach, A. Villunger, E. M. Michalak, A. Strasser, and A. M. Tolkovsky Mutually Exclusive Subsets of BH3-Only Proteins Are Activated by the p53 and c-Jun N-Terminal Kinase/c-Jun Signaling Pathways during Cortical Neuron Apoptosis Induced by Arsenite Mol. Cell. Biol., October 1, 2005; 25(19): 8732 - 8747. [Abstract] [Full Text] [PDF]

				J. Zhang, J. Liu, C. Yu, and A. Lin BAD Ser128 Is Not Phosphorylated by c-Jun NH2-Terminal Kinase for Promoting Apoptosis Cancer Res., September 15, 2005; 65(18): 8372 - 8378. [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]

				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]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help