Source:http://linkedlifedata.com/resource/pubmed/id/11080187
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2000-11-20
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pubmed:abstractText |
Previous studies have implicated stress-activated protein kinases (SAPKs) in aberrant phosphorylation of the high-molecular-mass neurofilament subunit (NFH). We now present direct evidence for this involvement using CEP-1347, a specific inhibitor of SAPK activation. Inhibition by this drug of stress-induced phosphorylation of NFH and the middle-molecular-mass neurofilament subunit in the perikaryon of dorsal root ganglion (DRG) neurons paralleled the decrease in levels of activated SAPKs and was essentially complete at 1 microM: CEP-1347. In addition, a role for SAPKs in the constitutive phosphorylation of NFH was demonstrated. Longterm treatment of unstressed DRG neurons with CEP-1347 lowered the steady-state phosphorylation level of NFH in neurites. No such effect was seen in neurons treated with PD 098059, which blocks activation of extracellular signal-regulated kinase 1/2. DRG neurites were shown to contain high basal levels of activated SAPKs. These included a 55-kDa SAPK whose activation was completely abolished at 0.05 microM: CEP-1347 and a 45-kDa SAPK that was not affected by the drug. These results indicate that SAPKs are involved in both stress-induced and constitutive phosphorylation of NFH. The differing responses of SAPKs in neurites and cell bodies to CEP-1347 inhibition further suggest the presence of different signaling pathways in the two neuronal compartments.
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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/3,9-bis((ethylthio)methyl)-K-252a,
http://linkedlifedata.com/resource/pubmed/chemical/Carbazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Neurofilament Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/neurofilament protein H
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0022-3042
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
75
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2358-67
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11080187-Animals,
pubmed-meshheading:11080187-Axons,
pubmed-meshheading:11080187-Carbazoles,
pubmed-meshheading:11080187-Cell Differentiation,
pubmed-meshheading:11080187-Cells, Cultured,
pubmed-meshheading:11080187-Enzyme Inhibitors,
pubmed-meshheading:11080187-Fluorescent Antibody Technique,
pubmed-meshheading:11080187-Ganglia, Spinal,
pubmed-meshheading:11080187-Immunohistochemistry,
pubmed-meshheading:11080187-Indoles,
pubmed-meshheading:11080187-Mitogen-Activated Protein Kinase 8,
pubmed-meshheading:11080187-Mitogen-Activated Protein Kinases,
pubmed-meshheading:11080187-Neurofilament Proteins,
pubmed-meshheading:11080187-PC12 Cells,
pubmed-meshheading:11080187-Phosphorylation,
pubmed-meshheading:11080187-Rats,
pubmed-meshheading:11080187-Signal Transduction
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pubmed:year |
2000
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pubmed:articleTitle |
Inhibition of aberrant and constitutive phosphorylation of the high-molecular-mass neurofilament subunit by CEP-1347 (KT7515), an inhibitor of the stress-activated protein kinase signaling pathway.
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pubmed:affiliation |
Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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