Linked Life Data

21464134

Source:http://linkedlifedata.com/resource/pubmed/id/21464134

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2011-5-30
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
3
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
19259-69
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Regulation of the epithelial Na+ channel by the RH domain of G protein-coupled receptor kinase, GRK2, and Galphaq/11.
pubmed:affiliation
Discipline of Physiology, The Bosch Institute, Faculty of Medicine, The University of Sydney, Sydney, NSW 2006, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't