RGD Reference Report - Beta-arrestin- and G protein receptor kinase-mediated calcium-sensing receptor desensitization. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Beta-arrestin- and G protein receptor kinase-mediated calcium-sensing receptor desensitization.

Authors: Pi, M  Oakley, RH  Gesty-Palmer, D  Cruickshank, RD  Spurney, RF  Luttrell, LM  Quarles, LD 
Citation: Pi M, etal., Mol Endocrinol. 2005 Apr;19(4):1078-87. Epub 2005 Jan 6.
RGD ID: 7207060
Pubmed: PMID:15637145   (View Abstract at PubMed)
DOI: DOI:10.1210/me.2004-0450   (Journal Full-text)

Extracellular calcium rapidly controls PTH secretion through binding to the G protein-coupled calcium-sensing receptor (CASR) expressed in parathyroid glands. Very little is known about the regulatory proteins involved in desensitization of CASR. G protein receptor kinases (GRK) and beta-arrestins are important regulators of agonist-dependent desensitization of G protein-coupled receptors. In the present study, we investigated their role in mediating agonist-dependent desensitization of CASR. In heterologous cell culture models, we found that the transfection of GRK4 inhibits CASR signaling by enhancing receptor phosphorylation and beta-arrestin translocation to the CASR. In contrast, we found that overexpression of GRK2 desensitizes CASR by classical mechanisms as well as through phosphorylation-independent mechanisms involving disruption of Galphaq signaling. In addition, we observed lower circulating PTH levels and an attenuated increase in serum PTH after hypocalcemic stimulation in beta-arrestin2 null mice, suggesting a functional role of beta-arrestin2-dependent desensitization pathways in regulating CASR function in vivo. We conclude that GRKs and beta-arrestins play key roles in regulating CASR responsiveness in parathyroid glands.

Objects Annotated

Genes (Rattus norvegicus)
Arrb1  (arrestin, beta 1)
Arrb2  (arrestin, beta 2)
Casr  (calcium-sensing receptor)
Grk2  (G protein-coupled receptor kinase 2)
Grk3  (G protein-coupled receptor kinase 3)
Grk4  (G protein-coupled receptor kinase 4)

Genes (Mus musculus)
Arrb1  (arrestin, beta 1)
Arrb2  (arrestin, beta 2)
Casr  (calcium-sensing receptor)
Grk2  (G protein-coupled receptor kinase 2)
Grk3  (G protein-coupled receptor kinase 3)
Grk4  (G protein-coupled receptor kinase 4)

Genes (Homo sapiens)
ARRB1  (arrestin beta 1)
ARRB2  (arrestin beta 2)
CASR  (calcium sensing receptor)
GRK2  (G protein-coupled receptor kinase 2)
GRK3  (G protein-coupled receptor kinase 3)
GRK4  (G protein-coupled receptor kinase 4)


Additional Information