Source:http://linkedlifedata.com/resource/pubmed/id/12684463
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
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| pubmed:dateCreated |
2003-4-9
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| pubmed:abstractText |
Cyclin-dependent kinase 5 (Cdk5) is activated on binding of activator proteins p35 and p39. A N-terminally truncated p35, termed p25, is generated through cleavage by the Ca(2+)-dependent protease calpain after induction of ischemia in rat brain. p25 has been shown to accumulate in brains of patients with Alzheimer's disease and may contribute to A-beta peptide-mediated toxicity. Studies from transfected neurons as well as p35 and p25 transgenic mice have indicated that Cdk5, when activated by p25, gains some toxic function compared with p35/Cdk5. It remains unclear, however, whether p25/Cdk5 signaling additionally channels into pathways usually used by p35/Cdk5 and whether p25 is associated with a loss of p35 function. To clarify these issues, we have generated p25-transgenic mice in a p35-null background. We find that low levels of p25 during development induce a partial rescue of the p35-/- phenotype in several brain regions analyzed, including a rescue of cell positioning of a subset of neurons in the neocortex. In accordance with the partial rescue of brain anatomy, phosphorylation of the Cdk5 substrate mouse disabled 1 is partially restored during development. Besides this, p25/Cdk5 fails to phosphorylate other substrates that are normally phosphorylated by p35/Cdk5. Our results show that p25 can substitute for p35/Cdk5 under certain circumstances during development. In addition, they suggest that p25 may have lost some functions of p35.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cdk5 activator p39,
http://linkedlifedata.com/resource/pubmed/chemical/Cdk5 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 5,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphopyruvate Hydratase,
http://linkedlifedata.com/resource/pubmed/chemical/neuronal Cdk5 activator (p25-p35)
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Apr
|
| pubmed:issn |
1529-2401
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
1
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| pubmed:volume |
23
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2769-78
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:12684463-Aging,
pubmed-meshheading:12684463-Animals,
pubmed-meshheading:12684463-Brain,
pubmed-meshheading:12684463-Cerebellum,
pubmed-meshheading:12684463-Cerebral Cortex,
pubmed-meshheading:12684463-Corpus Callosum,
pubmed-meshheading:12684463-Cyclin-Dependent Kinase 5,
pubmed-meshheading:12684463-Cyclin-Dependent Kinases,
pubmed-meshheading:12684463-Gene Expression,
pubmed-meshheading:12684463-Hippocampus,
pubmed-meshheading:12684463-Mice,
pubmed-meshheading:12684463-Mice, Knockout,
pubmed-meshheading:12684463-Mice, Transgenic,
pubmed-meshheading:12684463-Nerve Tissue Proteins,
pubmed-meshheading:12684463-Neurodegenerative Diseases,
pubmed-meshheading:12684463-Neurons,
pubmed-meshheading:12684463-Phenotype,
pubmed-meshheading:12684463-Phosphopyruvate Hydratase,
pubmed-meshheading:12684463-Phosphorylation,
pubmed-meshheading:12684463-Signal Transduction
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| pubmed:year |
2003
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| pubmed:articleTitle |
Partial rescue of the p35-/- brain phenotype by low expression of a neuronal-specific enolase p25 transgene.
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| pubmed:affiliation |
Department of Pathology and Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.
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