scholarly journals G Protein-coupled Receptor Kinase 2 Regulator of G Protein Signaling Homology Domain Binds to Both Metabotropic Glutamate Receptor 1a and Gαqto Attenuate Signaling

2004 ◽  
Vol 279 (16) ◽  
pp. 16614-16620 ◽  
Author(s):  
Gurpreet K. Dhami ◽  
Lianne B. Dale ◽  
Pieter H. Anborgh ◽  
Katharine E. O'Connor-Halligan ◽  
Rachel Sterne-Marr ◽  
...  
Keyword(s):  
G Protein ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
Metabotropic Glutamate ◽  
G Protein Coupled

scholarly journals G Protein-coupled Receptor Kinase-mediated Desensitization of Metabotropic Glutamate Receptor 1A Protects against Cell Death

2000 ◽  
Vol 275 (49) ◽  
pp. 38213-38220 ◽  
Author(s):  
Lianne B. Dale ◽  
Moshmi Bhattacharya ◽  
Pieter H. Anborgh ◽  
Barbara Murdoch ◽  
Mickie Bhatia ◽  
...  
Keyword(s):  
Cell Death ◽  
G Protein ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
Metabotropic Glutamate ◽  
G Protein Coupled

Regulation of mGlu4 Metabotropic Glutamate Receptor Signaling by Type-2 G-Protein Coupled Receptor Kinase (GRK2)

2004 ◽  
Vol 65 (5) ◽  
pp. 1103-1110 ◽  
Author(s):  
L. Iacovelli ◽  
L. Capobianco ◽  
M. Iula ◽  
V. Di Giorgi Gerevini ◽  
A. Picascia ◽  
...  
Keyword(s):  
G Protein ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Receptor Signaling ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
Metabotropic Glutamate ◽  
G Protein Coupled

scholarly journals Phosphorylation-independent Regulation of Metabotropic Glutamate Receptor Signaling by G Protein-coupled Receptor Kinase 2

2002 ◽  
Vol 277 (28) ◽  
pp. 25266-25272 ◽  
Author(s):  
Gurpreet Kaur Dhami ◽  
Pieter H. Anborgh ◽  
Lianne B. Dale ◽  
Rachel Sterne-Marr ◽  
Stephen S. G. Ferguson
Keyword(s):  
G Protein ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Receptor Signaling ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
Metabotropic Glutamate ◽  
G Protein Coupled

scholarly journals Regulation of the Epithelial Na+ Channel by the RH Domain of G Protein-coupled Receptor Kinase, GRK2, and Gαq/11

2011 ◽  
Vol 286 (22) ◽  
pp. 19259-19269 ◽  
Author(s):  
Il-Ha Lee ◽  
Sung-Hee Song ◽  
Craig R. Campbell ◽  
Sharad Kumar ◽  
David I. Cook ◽  
...  
Keyword(s):  
G Protein ◽  
Kinase Activity ◽  
Receptor Activation ◽  
Na Channel ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled ◽  
Α Subunits

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 (K220RGRK2), 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 (D110AGRK2), 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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