G-protein-coupled receptor kinases (GRKs) specifically phosphorylate agonist-occupied G-protein-coupled receptors (GPCRs). All seven mammalian GRKs contain an N-terminal domain that is homologous to the regulator of G-protein signaling (RGS) family of proteins. The RGS domain of GRK2 has been shown to interact specifically with Galphaq family members. While the specificity and functional consequences of GRK/Galpha interaction remain somewhat poorly defined, GRK RGS homology (RH) domains likely function to provide specificity for GRK interaction with a particular Galpha subunit or GPCR/Galpha complex. Indeed, GRK2 binds Galphaq, alpha11, and alpha14, but not Galpha16, Galphas, Galphai, or Galpha(12/13), while the RGS domains of GRK5 and GRK6 do not bind Galpha(q/11), Galphas, Galphai, or Galpha(12/13). In this chapter we describe various in vitro and intact cell strategies that can be used to elucidate the function of GRK RH domains.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/S0076-6879(04)90019-5 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Roles of sensory receptors in non-sensory organs: the kidney and beyond.
Nat Rev Nephrol
January 2025
Department of Physiology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Olfactory receptors (ORs), taste receptors and opsins are well-known for their pivotal roles in mediating the senses of smell, taste and sight, respectively. However, in the past two decades, research has shown that these sensory receptors also regulate physiological processes in a variety of non-sensory tissues. Although ORs, taste receptors and opsins have all been shown to have physiological roles beyond their traditional locations, most work in the kidney has focused on ORs.
View Article and Find Full Text PDFNetwork pharmacology and molecular docking to explore mechanisms of clozapine-induced cardiac arrest.
J Psychiatry Neurosci
January 2025
From the Computational Biology Centre and the Laboratory of Psychiatric-Neuroimaging-Genetic and Comorbidity, Tianjin Anding Hospital, Tianjin Mental Health Centre of Tianjin Medical University, Nankai University Affiliated Tianjin Anding Hospital, Tianjin, China.
Background: Clozapine is superior to all other antipsychotics in treating schizophrenia in terms of its curative efficacy; however, this drug is prescribed only as a last resort in the treatment of schizophrenia, given its potential to induce cardiac arrest. The mechanism of clozapine-induced cardiac arrest remains unclear, so we aimed to elucidate the potential mechanisms of clozapine-induced cardiac arrest using network pharmacology and molecular docking.
Methods: We identified and analyzed the overlap between potential cardiac arrest-related target genes and clozapine target genes.
Molecular basis of proton sensing by G protein-coupled receptors.
Cell
December 2024
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94143, USA; Chan Zuckerberg Biohub, San Francisco, CA 94148, USA; Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA 94115, USA. Electronic address:
Three proton-sensing G protein-coupled receptors (GPCRs)-GPR4, GPR65, and GPR68-respond to extracellular pH to regulate diverse physiology. How protons activate these receptors is poorly understood. We determined cryogenic-electron microscopy (cryo-EM) structures of each receptor to understand the spatial arrangement of proton-sensing residues.
View Article and Find Full Text PDFEvolutionary study and structural basis of proton sensing by Mus GPR4 and Xenopus GPR4.
Cell
December 2024
Key Laboratory Experimental Teratology of the Ministry of Education, New Cornerstone Science Laboratory, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, China; NHC Key Laboratory of Otorhinolaryngology, Qilu Hospital of Shandong University, Advanced Medical Research Institute, Shandong University, Jinan, China; Department of Physiology and Pathophysiology, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China. Electronic address:
Animals have evolved pH-sensing membrane receptors, such as G-protein-coupled receptor 4 (GPR4), to monitor pH changes related to their physiology and generate adaptive reactions. However, the evolutionary trajectory and structural mechanism of proton sensing by GPR4 remain unresolved. Here, we observed a positive correlation between the optimal pH of GPR4 activity and the blood pH range across different species.
View Article and Find Full Text PDFTranscriptomic DN3 clock neuron subtypes regulate sleep.
Sci Adv
January 2025
Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02453, USA.
Circadian neurons within animal brains orchestrate myriad physiological processes and behaviors, but the contribution of these neurons to the regulation of sleep is not well understood. To address this deficiency, we leveraged single-cell RNA sequencing to generate a comprehensive census of transcriptomic cell types of clock neurons. We focused principally on the enigmatic DN3s, which constitute most fly brain clock neurons and were previously almost completely uncharacterized.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!