Abstract
G protein coupled receptors (GPCRs) are extremely important drug targets and the β-arrestin intracellular scaffolding and adaptor proteins regulate major aspects of their pharmacology. β-arrestin binding to activated, GPCR kinase (GRK)-phosphorylated receptors has the capacity to terminate G protein coupling, internalize the receptors into clathrincoated 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 β-arrestin oligomerization, which are likely to be highly receptor and cell-type dependent. The role of β-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.
Keywords: G protein coupled receptor, GPCR, β-arrestin, endocytosis, internalisation
Endocrine, Metabolic & Immune Disorders - Drug Targets
Title: G Protein Coupled Receptors as Drug Targets: The Role of β-Arrestins
Volume: 8 Issue: 1
Author(s): Jasmin R. Dromey and Kevin D.G. Pfleger
Affiliation:
Keywords: G protein coupled receptor, GPCR, β-arrestin, endocytosis, internalisation
Abstract: G protein coupled receptors (GPCRs) are extremely important drug targets and the β-arrestin intracellular scaffolding and adaptor proteins regulate major aspects of their pharmacology. β-arrestin binding to activated, GPCR kinase (GRK)-phosphorylated receptors has the capacity to terminate G protein coupling, internalize the receptors into clathrincoated 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 β-arrestin oligomerization, which are likely to be highly receptor and cell-type dependent. The role of β-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.
Export Options
About this article
Cite this article as:
Dromey R. Jasmin and Pfleger D.G. Kevin, G Protein Coupled Receptors as Drug Targets: The Role of β-Arrestins, Endocrine, Metabolic & Immune Disorders - Drug Targets 2008; 8 (1) . https://dx.doi.org/10.2174/187153008783928352
DOI https://dx.doi.org/10.2174/187153008783928352 |
Print ISSN 1871-5303 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3873 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Proteasome Inhibitors: Recent Advances and New Perspectives In Medicinal Chemistry
Current Topics in Medicinal Chemistry Eosinophilopoiesis at the Cross-Roads of Research on Development, Immunity and Drug Discovery
Current Medicinal Chemistry Apoptosis: A Potential Therapeutic Target for Retinal Degenerations
Current Neurovascular Research Reactive Oxygen Species in Pathogenesis of Atherosclerosis
Current Pharmaceutical Design An Update on Clinical and Pharmacological Aspects of Drug-Eluting Stents
Cardiovascular & Hematological Disorders-Drug Targets The Impact of Hypothermia on the Pharmacokinetics of Drugs Used in Neonates and Young Infants
Current Pharmaceutical Design Tumor Angiogenesis: A Potential Target In Cancer Control by Phytochemicals
Current Cancer Drug Targets Unraveling the Dopamine Receptor Signalplex by DRIPs and DRAPs
Current Proteomics Analysis of QTc Interval during Levofloxacin Prescription in Cardiac Patients with Pneumonia
Current Drug Safety Organoselenium Compounds as Potential Neuroprotective Therapeutic Agents
Current Organic Chemistry Anticonvulsant and Antinociceptive Actions of Novel Adenosine Kinase Inhibitors
Current Topics in Medicinal Chemistry Radiological Screening Programs for Women at High Risk of Developing Breast Cancer
Current Women`s Health Reviews Inducers of Heme Oxygenase-1
Current Pharmaceutical Design Endothelial Cell Aging and Apoptosis in Prevention and Disease: E-Selectin Expression and Modulation As A Model
Current Pharmaceutical Design Cell Metabolism Under Microenvironmental Low Oxygen Tension Levels in Stemness, Proliferation and Pluripotency
Current Molecular Medicine Low Concentration of Caffeine Inhibits the Progression of the Hepatocellular Carcinoma <i>via Akt</i> Signaling Pathway
Anti-Cancer Agents in Medicinal Chemistry Molecule of the Month
Current Topics in Medicinal Chemistry Routine use of Corticosteroids to Prevent Inflammation Response in Cardiac Surgery
Recent Patents on Cardiovascular Drug Discovery Antioxidative Effects of Rhodiola Genus: Phytochemistry and Pharmacological Mechanisms against the Diseases
Current Topics in Medicinal Chemistry Curcumin as an Adjuvant to Breast Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry