pubmed-article:21464134 | rdf:type | pubmed:Citation | lld:pubmed |
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pubmed-article:21464134 | lifeskim:mentions | umls-concept:C0682972 | lld:lifeskim |
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pubmed-article:21464134 | lifeskim:mentions | umls-concept:C1514562 | lld:lifeskim |
pubmed-article:21464134 | lifeskim:mentions | umls-concept:C1883221 | lld:lifeskim |
pubmed-article:21464134 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
pubmed-article:21464134 | lifeskim:mentions | umls-concept:C0597484 | lld:lifeskim |
pubmed-article:21464134 | lifeskim:mentions | umls-concept:C0439799 | lld:lifeskim |
pubmed-article:21464134 | lifeskim:mentions | umls-concept:C1883204 | lld:lifeskim |
pubmed-article:21464134 | lifeskim:mentions | umls-concept:C1880389 | lld:lifeskim |
pubmed-article:21464134 | pubmed:issue | 22 | lld:pubmed |
pubmed-article:21464134 | pubmed:dateCreated | 2011-5-30 | lld:pubmed |
pubmed-article:21464134 | pubmed:abstractText | The G protein-coupled receptor kinase (GRK2) belongs to a family of protein kinases that phosphorylates agonist-activated G protein-coupled receptors, leading to G protein-receptor uncoupling and termination of G protein signaling. GRK2 also contains a regulator of G protein signaling homology (RH) domain, which selectively interacts with ?-subunits of the Gq/11 family that are released during G protein-coupled receptor activation. We have previously reported that kinase activity of GRK2 up-regulates activity of the epithelial sodium channel (ENaC) in a Na(+) absorptive epithelium by blocking Nedd4-2-dependent inhibition of ENaC. In the present study, we report that GRK2 also regulates ENaC by a mechanism that does not depend on its kinase activity. We show that a wild-type GRK2 (wtGRK2) and a kinase-dead GRK2 mutant ((K220R)GRK2), but not a GRK2 mutant that lacks the C-terminal RH domain (?RH-GRK2) or a GRK2 mutant that cannot interact with G?q/11/14 ((D110A)GRK2), increase activity of ENaC. GRK2 up-regulates the basal activity of the channel as a consequence of its RH domain binding the ?-subunits of Gq/11. We further found that expression of constitutively active G?q/11 mutants significantly inhibits activity of ENaC. Conversely, co-expression of siRNA against G?q/11 increases ENaC activity. The effect of G?q on ENaC activity is not due to change in ENaC membrane expression and is independent of Nedd4-2. These findings reveal a novel mechanism by which GRK2 and Gq/11 ?-subunits regulate the activity ENaC. | lld:pubmed |
pubmed-article:21464134 | pubmed:language | eng | lld:pubmed |
pubmed-article:21464134 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:21464134 | pubmed:citationSubset | IM | lld:pubmed |
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pubmed-article:21464134 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:21464134 | pubmed:month | Jun | lld:pubmed |
pubmed-article:21464134 | pubmed:issn | 1083-351X | lld:pubmed |
pubmed-article:21464134 | pubmed:author | pubmed-author:KumarSharadS | lld:pubmed |
pubmed-article:21464134 | pubmed:author | pubmed-author:CookDavid IDI | lld:pubmed |
pubmed-article:21464134 | pubmed:author | pubmed-author:LeeIl-HaIH | lld:pubmed |
pubmed-article:21464134 | pubmed:author | pubmed-author:DinudomAnuwat... | lld:pubmed |
pubmed-article:21464134 | pubmed:author | pubmed-author:CampbellCraig... | lld:pubmed |
pubmed-article:21464134 | pubmed:author | pubmed-author:SongSung-HeeS... | lld:pubmed |
pubmed-article:21464134 | pubmed:issnType | Electronic | lld:pubmed |
pubmed-article:21464134 | pubmed:day | 3 | lld:pubmed |
pubmed-article:21464134 | pubmed:volume | 286 | lld:pubmed |
pubmed-article:21464134 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:21464134 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:21464134 | pubmed:pagination | 19259-69 | lld:pubmed |
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pubmed-article:21464134 | pubmed:year | 2011 | lld:pubmed |
pubmed-article:21464134 | pubmed:articleTitle | Regulation of the epithelial Na+ channel by the RH domain of G protein-coupled receptor kinase, GRK2, and Galphaq/11. | lld:pubmed |
pubmed-article:21464134 | pubmed:affiliation | Discipline of Physiology, The Bosch Institute, Faculty of Medicine, The University of Sydney, Sydney, NSW 2006, Australia. | lld:pubmed |
pubmed-article:21464134 | pubmed:publicationType | Journal Article | lld:pubmed |
pubmed-article:21464134 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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