| Abstract | G protein coupled receptors (GPCRs) are extremely important drug targets and the beta-arrestin intracellular scaffolding and adaptor proteins regulate major aspects of their pharmacology. beta-arrestin binding to activated, GPCR kinase (GRK)-phosphorylated receptors has the capacity to terminate G protein coupling, internalize the receptors into clathrin-coated vesicles and establish a secondary signaling complex independent of G protein signaling. These events appear to be differentially regulated by GRK phosphorylation, ubiquitination and potentially beta-arrestin oligomerization, which are likely to be highly receptor and cell-type dependent. The role of beta-arrestins in switching from G-protein dependent to independent signaling places them in a pivotal position to dictate the downstream effects of ligand binding. Consequently, we must appreciate the functioning of these molecules as we strive to discover and optimize new GPCR drug therapies for endocrine, metabolic and immune disorders. |
| Authors | Jasmin R Dromey, Kevin D G Pfleger
(Affiliation: Laboratory for Molecular Endocrinology-GPCRs, Western Australian Institute for Medical Research, WA, Australia.)
|
| Journal | Endocrine, metabolic & immune disorders drug targets
(Endocr Metab Immune Disord Drug Targets)
Vol. 8
Issue 1
Pg. 51-61
(Mar 2008)
ISSN: 1871-5303 United Arab Emirates |
| PMID | 18393923
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
|
| Chemical References |
- Arrestins
- Receptors, G-Protein-Coupled
- beta-arrestin
- Ubiquinone
|
| Topics |
- Animals
- Arrestins
(drug effects, physiology)
- Humans
- Receptors, G-Protein-Coupled
(classification, drug effects, physiology)
- Ubiquinone
(metabolism)
|
