Source:http://linkedlifedata.com/resource/pubmed/id/11152698
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
14
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pubmed:dateCreated |
2001-4-3
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pubmed:abstractText |
Kainate receptor glutamate receptor 6 (GluR6) subunit-deficient and c-Jun N-terminal kinase 3 (JNK3)-null mice share similar phenotypes including resistance to kainite-induced epileptic seizures and neuronal toxicity (Yang, D. D., Kuan, C-Y., Whitmarsh, A. J., Rincon, M., Zheng, T. S., Davis, R. J., Rakis, P., and Flavell, R. (1997) Nature 389, 865-869; Mulle, C., Seiler, A., Perez-Otano, I., Dickinson-Anson, H., Castillo, P. E., Bureau, I., Maron, C., Gage, F. H., Mann, J. R., Bettler, B., and Heinemmann, S. F. (1998) Nature 392, 601-605). This suggests that JNK activation may be involved in GluR6-mediated excitotoxicity. We provide evidence that post-synaptic density protein (PSD-95) links GluR6 to JNK activation by anchoring mixed lineage kinase (MLK) 2 or MLK3, upstream activators of JNKs, to the receptor complex. Association of MLK2 and MLK3 with PSD-95 in HN33 cells and rat brain preparations is dependent upon the SH3 domain of PSD-95, and expression of GluR6 in HN33 cells activated JNKs and induced neuronal apoptosis. Deletion of the PSD-95-binding site of GluR6 reduced both JNK activation and neuronal toxicity. Co-expression of dominant negative MLK2, MLK3, or mitogen-activated kinase kinase (MKK) 4 and MKK7 also significantly attenuated JNK activation and neuronal toxicity mediated by GluR6, and co-expression of PSD-95 with a deficient Src homology 3 domain also inhibited GluR6-induced JNK activation and neuronal toxicity. Our results suggest that PSD-95 plays a critical role in GluR6-mediated JNK activation and excitotoxicity by anchoring MLK to the receptor complex.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Dlgh4 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 4,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase...,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Kainic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/mitogen-activated protein kinase...,
http://linkedlifedata.com/resource/pubmed/chemical/postsynaptic density proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
11382-6
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11152698-Animals,
pubmed-meshheading:11152698-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:11152698-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:11152698-MAP Kinase Kinase 4,
pubmed-meshheading:11152698-MAP Kinase Kinase Kinases,
pubmed-meshheading:11152698-MAP Kinase Signaling System,
pubmed-meshheading:11152698-Membrane Proteins,
pubmed-meshheading:11152698-Mitogen-Activated Protein Kinase Kinases,
pubmed-meshheading:11152698-Nerve Tissue Proteins,
pubmed-meshheading:11152698-Neurons,
pubmed-meshheading:11152698-Rats,
pubmed-meshheading:11152698-Receptors, Kainic Acid,
pubmed-meshheading:11152698-Signal Transduction
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pubmed:year |
2001
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pubmed:articleTitle |
Kainate receptor activation induces mixed lineage kinase-mediated cellular signaling cascades via post-synaptic density protein 95.
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pubmed:affiliation |
Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.
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