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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
46
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pubmed:dateCreated |
1998-12-8
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pubmed:abstractText |
Previous studies have shown that an inducible Raf-1 kinase protein, DeltaRaf-1:ER, activates the mitogen-activated protein kinase/extracellular signal-regulated protein kinase (ERK)-signaling pathway, which is required for the transformation of the rat salivary epithelial cell line, Pa-4. Differential display polymerase chain reaction was employed to search for mRNAs repressed by DeltaRaf-1:ER activation. Through this approach, the gene encoding the alpha-subunit of the amiloride-sensitive epithelial sodium channel (alpha-ENaC) was identified as a target of activated Raf-1 kinases. alpha-ENaC down-regulation could also be seen in cells treated with 12-O-tetradecanoyl-1-phorbol-13-acetate (TPA), indicating that the repression of steady-state alpha-ENaC mRNA level was dependent upon the activity of protein kinase C, the target of TPA, as well. Pretreatment of cells with a specific inhibitor of the ERK kinase pathway, PD 98059, markedly abolished the down-regulation of alpha-ENaC expression, consistent with the hypothesis that the ERK kinase-signaling pathway is involved in TPA-mediated repression. Moreover, through the use of transient transfection assays with alpha-ENaC-reporter and activated Raf expression construct(s), we provide the first evidence that activation of the ERK pathway down-regulates alpha-ENaC expression at the transcriptional level. Elucidating the molecular programming that modulates the expression of the alpha-subunit may provide new insights into the modulation of sodium reabsorption across epithelia.
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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-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Epithelial Sodium Channel,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-raf,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
13
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pubmed:volume |
273
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
30770-6
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:9804854-Animals,
pubmed-meshheading:9804854-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:9804854-Cells, Cultured,
pubmed-meshheading:9804854-Down-Regulation,
pubmed-meshheading:9804854-Enzyme Activation,
pubmed-meshheading:9804854-Epithelial Cells,
pubmed-meshheading:9804854-Epithelial Sodium Channel,
pubmed-meshheading:9804854-Gene Expression Regulation,
pubmed-meshheading:9804854-Parotid Gland,
pubmed-meshheading:9804854-Proto-Oncogene Proteins c-raf,
pubmed-meshheading:9804854-RNA, Messenger,
pubmed-meshheading:9804854-Rats,
pubmed-meshheading:9804854-Sodium Channels,
pubmed-meshheading:9804854-Tetradecanoylphorbol Acetate,
pubmed-meshheading:9804854-Transcription, Genetic
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pubmed:year |
1998
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pubmed:articleTitle |
The amiloride-sensitive epithelial sodium channel alpha-subunit is transcriptionally down-regulated in rat parotid cells by the extracellular signal-regulated protein kinase pathway.
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pubmed:affiliation |
Department of Molecular Pharmacology and Toxicology, Los Angeles, California 90033, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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