Source:http://linkedlifedata.com/resource/pubmed/id/15878642
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2005-5-26
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| pubmed:abstractText |
Conventional protein kinase C (cPKC) isoforms are activated by a coincident rise in cytosolic Ca(2+) and membrane-bound diacylglycerol. In excitable cells, cPKC may be activated by Ca(2+) influx through voltage-gated Ca(2+) channels (VGCC). cPKCs, in turn, are known to modulate the activity of VGCC. We examined whether PKCalpha, a cPKC, could be activated by depolarization in a neuroendocrine cell line and whether activation occurred on a time scale that modulated the depolarization-evoked intracellular Ca(2+) concentration ([Ca(2+)](i)) signal. Pheochromocytoma cells (PC12 cells) were transfected with wild-type and mutant forms of PKCalpha labeled with yellow fluorescent protein to monitor kinase translocation. Simultaneously, [Ca(2+)](i) changes were monitored with fura-2. Two point mutations that render PKCalpha inactive, D187A in the Ca(2+) binding site and K368R in the ATP binding site, significantly prolonged the time-to-peak of the depolarization-evoked [Ca(2+)](i) signal. A mutation that modulates membrane insertion (W58G) and two mutations of an autophosphorylation site (S657A, S657E) had no effect on the kinetics of the [Ca(2+)](i) signal. We conclude that in PC12 cells, Ca(2+) entry through VGCC rapidly activates PKCalpha, and that PKCalpha can modulate the Ca(2+) signal on a physiologically relevant time scale. Point mutations of PKCalpha can be used as specific and potent modulators of the PKC signaling pathway.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Fura-2,
http://linkedlifedata.com/resource/pubmed/chemical/Luminescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PRKCA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Chloride,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/yellow fluorescent protein, Bacteria
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| pubmed:status |
MEDLINE
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| pubmed:issn |
0306-4522
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
133
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
393-403
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:15878642-Animals,
pubmed-meshheading:15878642-Bacterial Proteins,
pubmed-meshheading:15878642-Calcium,
pubmed-meshheading:15878642-Diagnostic Imaging,
pubmed-meshheading:15878642-Extracellular Space,
pubmed-meshheading:15878642-Fura-2,
pubmed-meshheading:15878642-Humans,
pubmed-meshheading:15878642-Luminescent Proteins,
pubmed-meshheading:15878642-Mutagenesis,
pubmed-meshheading:15878642-Mutation,
pubmed-meshheading:15878642-PC12 Cells,
pubmed-meshheading:15878642-Pheochromocytoma,
pubmed-meshheading:15878642-Phosphorylation,
pubmed-meshheading:15878642-Potassium Chloride,
pubmed-meshheading:15878642-Protein Kinase C,
pubmed-meshheading:15878642-Protein Kinase C-alpha,
pubmed-meshheading:15878642-Protein Transport,
pubmed-meshheading:15878642-Rats,
pubmed-meshheading:15878642-Transfection
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| pubmed:year |
2005
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| pubmed:articleTitle |
Protein kinase Calpha modulates depolarizaton-evoked changes of intracellular Ca2+ concentration in a rat pheochromocytoma cell line.
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| pubmed:affiliation |
Department of Pharmacology and Physiology, University of Medicine and Dentistry New Jersey-New Jersey Medical School, Newark, NJ 07101-1709, USA.
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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