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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
26
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pubmed:dateCreated |
1991-10-21
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pubmed:abstractText |
Agents that activate cAMP-dependent protein kinase (PKA) as well as agents that increase intracellular calcium induce the expression of certain immediate early genes (IEGs). Recently, it has been demonstrated that the same cis-acting element in the 5' region of the c-fos gene has the ability to mediate both cAMP- and calcium-induced c-fos expression in PC12 cells (Sheng, M., McFadden, G., and Greenberg, M. (1990) Neuron 4, 571-582). Here we demonstrate that both cAMP- and calcium-mediated induction of c-fos and egr1 are dependent on PKA activity. Addition of either depolarizing concentrations of KCl or the calcium ionophore, ionomycin, to PC12 cells increased the expression of both c-fos and egr1, but these inductions were dramatically reduced in three PKA-deficient cell lines, 123.7, AB.11, and A126-1B2. Furthermore, pretreatment of PC12 cells with 20 microM H89, a specific inhibitor of PKA, inhibited forskolin, dibutyryl cAMP, and KCl-induced c-fos and egr1 induction, while having no effect on NGF induction. Likewise, in the PKA-deficient cells, NGF or an activator of protein kinase C induced c-fos and egr1 normally. To determine if PKA deficiency modifies the ability of Ca2+ to activate calcium-dependent kinases, autophosphorylation of multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase) in response to Ca2+ influx was determined. In parental PC12 cells, PC12 cells pretreated with H89, and PKA-deficient cell lines, CaM kinase was activated equivalently in response to KCl depolarization. These results suggest that PKA is not required for Ca(2+)-induced increase in CaM kinase activity and that the induction of IEGs in response to Ca2+ influx is PKA-dependent. Thus, the requirement for PKA resides at a point distal to the activation of calmodulin-dependent processes.
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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/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ionomycin,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Chloride,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fos,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
266
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
17454-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:1910045-Blotting, Northern,
pubmed-meshheading:1910045-Calcium,
pubmed-meshheading:1910045-Cell Line,
pubmed-meshheading:1910045-DNA-Binding Proteins,
pubmed-meshheading:1910045-Gene Expression Regulation,
pubmed-meshheading:1910045-Ionomycin,
pubmed-meshheading:1910045-Kinetics,
pubmed-meshheading:1910045-Potassium Chloride,
pubmed-meshheading:1910045-Protein Kinases,
pubmed-meshheading:1910045-Proto-Oncogene Proteins,
pubmed-meshheading:1910045-Proto-Oncogene Proteins c-fos,
pubmed-meshheading:1910045-Signal Transduction,
pubmed-meshheading:1910045-Transcription Factors
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pubmed:year |
1991
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pubmed:articleTitle |
Induction of immediate early genes by Ca2+ influx requires cAMP-dependent protein kinase in PC12 cells.
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pubmed:affiliation |
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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