G protein-coupled receptor kinase 4gamma interacts with inactive Galpha(s) and Galpha13

Biochemical and Biophysical Research Communications
Lindsay KeeverBradley T Andresen

Abstract

G protein-coupled receptors (GPCRs) are regulated by multiple families of kinases including GPCR kinases (GRKs). GRK4 is constitutively active towards GPCRs, and polymorphisms of GRK4gamma are linked to hypertension. We examined, through co-immunoprecipitation, the interactions between GRK4gamma and the Galpha and Gbeta subunits of heterotrimeric G proteins. Because GRK4 has been shown to inhibit Galpha(s)-coupled GPCR signaling and lacks a PH domain, we hypothesized that GRK4gamma would interact with active Galpha(s), but not Gbeta. Surprisingly, GRK4gamma preferentially interacts with inactive Galpha(s) and Gbeta to a greater extent than active Galpha(s). GRK4gamma also interacts with inactive Galpha(13) and Gbeta. Functional studies demonstrate that wild-type GRK4gamma, but not kinase-dead GRK4gamma, ablates isoproterenol-mediated cAMP production indicating that the kinase domain is responsible for GPCR regulation. This evidence suggests that binding to inactive Galpha(s) and Gbeta may explain the constitutive activity of GRK4gamma towards Galpha(s)-coupled receptors.

References

Dec 1, 1992·Human Molecular Genetics·C AmbroseJ J Wasmuth
May 23, 1998·Annual Review of Pharmacology and Toxicology·J G Krupnick, J L Benovic
Sep 1, 1999·The Journal of Endocrinology·C B BrenninkmeijerS Phaneuf
Dec 2, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·M SalleseA De Blasi
Mar 21, 2002·Proceedings of the National Academy of Sciences of the United States of America·Robin A FelderPedro A Jose
May 17, 2005·Cellular Signalling·Thierry MétayéJean-Louis Kraimps
Apr 15, 2006·The Journal of Biological Chemistry·David T LodowskiJohn J G Tesmer

❮ Previous
Next ❯

Citations

Feb 16, 2010·Biochimica Et Biophysica Acta·Pedro A JoseRobin A Felder
Apr 15, 2015·Hypertension·Jian YangChunyu Zeng
Jul 3, 2015·The Journal of Biological Chemistry·Samantha J AllenKevin J Lumb
Sep 27, 2019·Experimental and Therapeutic Medicine·Inga NachreinerMehmet Kemal Tur

❮ Previous
Next ❯

Related Concepts

Related Feeds

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.