Source:http://linkedlifedata.com/resource/pubmed/id/10794679
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2000-6-12
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pubmed:abstractText |
In an effort to gain insight into how kinases might regulate epithelial Na(+) channel (ENaC) activity, we expressed human ENaC (hENaC) in Xenopus oocytes and examined the effect of agents that modulate the activity of some kinases. Activation of protein kinase C (PKC) by phorbol ester increased the activity of ENaC, but only in oocytes with a baseline current of <2,000 nA. Inhibitors of protein kinases produced varying effects. Chelerythrine, an inhibitor of PKC, produced a significant inhibition of ENaC current, but calphostin C, another PKC inhibitor, had no effect. The PKA/protein kinase G inhibitor H-8 had no effect, whereas the p38 mitogen-activated protein kinase inhibitor, SB-203580 had a significant inhibitory effect. Staurosporine, a nonspecific kinase inhibitor, was the most potent tested. It inhibited ENaC currents in both oocytes and in M-1 cells, a model for the collecting duct. Site-directed mutagenesis revealed that the staurosporine effect did not require an intact COOH terminus of either the beta- or gamma-hENaC subunit. However, an intact COOH terminus of the alpha-subunit was required for this effect. These results suggest that an integrated kinase network regulates ENaC activity through an action that requires a portion of the alpha-subunit.
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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/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Epithelial Sodium Channel,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Staurosporine,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0363-6143
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
C1047-54
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10794679-Animals,
pubmed-meshheading:10794679-Enzyme Inhibitors,
pubmed-meshheading:10794679-Epithelial Sodium Channel,
pubmed-meshheading:10794679-Female,
pubmed-meshheading:10794679-Humans,
pubmed-meshheading:10794679-Mutagenesis, Site-Directed,
pubmed-meshheading:10794679-Oocytes,
pubmed-meshheading:10794679-Protein Kinase C,
pubmed-meshheading:10794679-Protein Kinase Inhibitors,
pubmed-meshheading:10794679-Protein Kinases,
pubmed-meshheading:10794679-Protein Structure, Quaternary,
pubmed-meshheading:10794679-Recombinant Proteins,
pubmed-meshheading:10794679-Sodium Channels,
pubmed-meshheading:10794679-Staurosporine,
pubmed-meshheading:10794679-Tetradecanoylphorbol Acetate,
pubmed-meshheading:10794679-Xenopus laevis
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pubmed:year |
2000
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pubmed:articleTitle |
Kinase regulation of hENaC mediated through a region in the COOH-terminal portion of the alpha-subunit.
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pubmed:affiliation |
Department of Internal Medicine, University of Iowa and Department of Veterans Affairs Medical Center, Iowa City, Iowa 52242, USA.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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