ArticleThe Journal of biological chemistry2011
Regulation of the epithelial Na+ channel by the RH domain of G protein-coupled receptor kinase, GRK2, and Galphaq/11.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Recent advances in the development of GRK2 inhibitors: blocking the interaction of GRK2 with its partners.Acta pharmacologica Sinica · 2026Review
- GRK2 activates TRAF2-NF-Acta pharmaceutica Sinica. B · 2025Article
- Novel inhibitors of phosphorylation independent activity of GRK2 modulate cAMP signaling.Pharmacology research & perspectives · 2022Article
- Association Between Polymorphisms of ADRBK1 Gene and Plasma Renin Activity in Hypertensive Patients: A Case-Control Study.Medical science monitor : international medical journal of experimental and clinical research · 2016Article
- G Protein-Coupled Receptor Kinases: Crucial Regulators of Blood Pressure.Journal of the American Heart Association · 2016Review
- Dual role of GRK5 in cancer development and progression.Translational medicine @ UniSa · 2016Article
- H-Ras mediates the inhibitory effect of epidermal growth factor on the epithelial Na+ channel.PloS one · 2015Article
- Strike a pose: Gαq complexes at the membrane.Trends in pharmacological sciences · 2014Review
- Epithelial Na(+) channel regulation by cytoplasmic and extracellular factors.Experimental cell research · 2012Review
- SMURF and NEDD4: sharp shooters monitor the gate keepers and ion traffic controllers of lead astray cell.The Journal of membrane biology · 2011Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 α-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 (ΔRH-GRK2) or a GRK2 mutant that cannot interact with Gαq/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 α-subunits of Gq/11. We further found that expression of constitutively active Gαq/11 mutants significantly inhibits activity of ENaC. Conversely, co-expression of siRNA against Gαq/11 increases ENaC activity. The effect of Gαq 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 α-subunits regulate the activity ENaC.
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