Source:http://linkedlifedata.com/resource/pubmed/id/19941067
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2010-3-10
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| pubmed:abstractText |
Apoptosis-associated tyrosine kinase (AATYK) is up-regulated by phosphorylation in cultured cerebellar granule neurons (CGN) undergoing apoptosis upon switch to low KCl-containing medium. However, the underlying signaling pathways remain to be fully characterized. When CGN at culture day 7 were switched from 25 mM KCl (K25) to 5 mM (K5) medium, AATYK band migration on SDS-PAGE shifted to a more slowly migrating position expected for the hyperphosphorylated protein. The apoptosis-inducing agent C(2)-ceramide also caused a mobility shift of the AATYK protein. Exposing CGN (K25) to L-type voltage-dependent Ca(2+) channel antagonists shifted the AATYK band to the K5-induced position, while the Ca(2+) channel activator FPL-64176 had the contrary effect. FK-506, a calcineurin inhibitor caused AATYK hyperphosphorylation under high KCl conditions. CGN death in K5 medium is linked to inhibition of the PI 3-kinase/Akt survival pathway and concomitant activation of the pro-apoptotic downstream target glycogen synthase kinase-3 (GSK-3). GSK-3 inhibitors blocked the K5-induced mobility shift of AATYK. Moreover, CGN cultured from AATYK-deficient mice remained sensitive to death in K5 medium. Thus, AATYK activation may not be a physiologically relevant principal regulatory target of the GSK-3 death pathway in KCl-deprived CGN.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Apr
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| pubmed:issn |
1573-6903
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
35
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
588-97
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:19941067-Amyloid beta-Peptides,
pubmed-meshheading:19941067-Animals,
pubmed-meshheading:19941067-Apoptosis,
pubmed-meshheading:19941067-Blotting, Western,
pubmed-meshheading:19941067-Calcium Signaling,
pubmed-meshheading:19941067-Cells, Cultured,
pubmed-meshheading:19941067-Cerebellum,
pubmed-meshheading:19941067-Cytoplasmic Granules,
pubmed-meshheading:19941067-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:19941067-Mice,
pubmed-meshheading:19941067-Neurons,
pubmed-meshheading:19941067-Phosphorylation,
pubmed-meshheading:19941067-Potassium,
pubmed-meshheading:19941067-Protein-Tyrosine Kinases,
pubmed-meshheading:19941067-Rats
|
| pubmed:year |
2010
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| pubmed:articleTitle |
Apoptosis-associated tyrosine kinase and neuronal cell death.
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| pubmed:affiliation |
Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline Research and Development Limited, New Frontiers Science Park, Harlow, UK.
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| pubmed:publicationType |
Journal Article
|