Using time-resolved cryo-electron microscopy (cryo-EM) and variability analysis to monitor the transitions high-resolution, dynamic view of GPCR activation, scientists can better tackle diseases by targeting specific Time-resolved cryo-EM of G-protein activation by a GPCR. Nature (2024).

September 2022 High GPER expression in triple-negative breast cancer is linked to pro-metastatic pathways while a new estrogen receptor, namely G protein-coupled estrogen receptor (GPER), is demonstrated to mediate At a median follow-up interval of 67.1 months, a significant trend towards reduced distant metastasis-free Transcriptome-based bioinformatics analysis revealed that GPER was linked to pro-metastatic pathways These results may supply new insights into GPER-mediated estrogen carcinogenesis in TNBC, thus providing

August 2022 "A confluence of factors has renewed interest in the scientific understanding and translational potential of psychedelic drugs such as lysergic acid diethylamide (LSD), mescaline, and psilocybin: the desire for additional approaches to mental health care, incremental progress in basic and clinical research, and the reconsideration and relaxation of existing drug policies. With the United States Food and Drug Administration's designation of psilocybin as a "Breakthrough Therapy" for treatment-resistant depression, a new path has been forged for the conveyance of psychedelics to the clinic. Essential to the further development of such applications, however, is a clearer understanding of how these drugs exert their effects at the molecular level. Here we review the current knowledge regarding the molecular details of psychedelic drug actions and suggest that these discoveries can facilitate new insights into their hallucinogenic and therapeutic mechanisms." Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 "G protein-coupled receptor (GPCR) kinases (GRKs) and arrestins mediate GPCR desensitization The spatial pattern of GPCR phosphorylation is predicted to trigger these discrete GRK and arrestin-mediated carboxyl-terminal tail (C-tail), but not proximal, phosphorylation of the chemokine receptor CXCR4 specifies We demonstrate by pharmacologic inhibition of GRK2/3-mediated phosphorylation of the chemokine receptor In conclusion, this study provides evidence that distal C-tail phosphorylation sites specify GRK-βarrestin-mediated

October 2022 Glucagon receptor-mediated regulation of gluconeogenic gene transcription is endocytosis-dependent We tested if this is true for the glucagon receptor (GCGR), which mediates physiological regulation of

October 2022 "Pepducins are small-lipidated peptides designed from the intracellular loops of G protein-coupled receptors (GPCRs) that act in an allosteric manner to modulate the activity of GPCRs. Over the past 2 decades, pepducins have progressed initially from pharmacologic tools used to manipulate GPCR activity in an orthosteric site-independent manner to compounds with therapeutic potential that have even been used safely in phase 1 and 2 clinical trials in human subjects. The effect of pepducins at their cognate receptors has been shown to vary between antagonist, partial agonist, and biased agonist outcomes in various primary and clonal cell systems, with even small changes in amino acid sequence altering these properties and their receptor selectivity. To date, pepducins designed from numerous GPCRs have been studied for their impact on pathologic conditions, including cardiovascular diseases such as thrombosis, myocardial infarction, and atherosclerosis. This review will focus in particular on pepducins designed from protease-activated receptors, C-X-C motif chemokine receptors, formyl peptide receptors, and the β2-adrenergic receptor. We will discuss the historic context of pepducin development for each receptor, as well as the structural, signaling, pathophysiologic consequences, and therapeutic potential for each pepducin class." Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 Coincident Regulation of PLCβ Signaling by Gq-Coupled and μOpioid Receptors Opposes Opioid- Mediated

G protein-coupled receptor kinase 2 is essential to enable vasoconstrictor-mediated arterial smooth muscle growth, we show that PI3K inhibition and depletion of GRK2 expression produced a similar ablation of pro-proliferative Vasoconstrictor-stimulated phosphorylation of the Akt substrates GSK3α and GSK3β was ablated following RNAi-mediated proliferation through its ability to promote efficient prolonged PI3K-Akt signalling, and thus relieve the GSK3-mediated

25-81) and GPR15L(71-81) are used as pharmacological tool compounds to delineate the GPR15 receptor-mediated

August 2022 " Background and purpose: Vascular tone is regulated by the relative contractile state of vascular smooth muscle cells (VSMCs). Several integrins directly modulate VSMC contraction by regulating calcium influx through L-type voltage-gated Ca2+ channels (VGCCs). Genetic variants in ITGA9, which encodes the α9 subunit of integrin α9β1, and SVEP1, a ligand for integrin α9β1, associate with elevated blood pressure; however, neither SVEP1 nor integrin α9β1 has reported roles in vasoregulation. We determined whether SVEP1 and integrin α9β1 can regulate VSMC contraction." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 Dopamine D 1 receptor-mediated β-arrestin signaling: Insight from pharmacology, biology, We now summarize important pharmacological, molecular, and cellular studies relevant to D1-mediated β-arrestin-related many results emerged from behavioral and physiological studies implying that bias toward or against D1-mediated

Constitutive, Basal, and β-Alanine-Mediated Activation of the Human Mas-Related G Protein-Coupled Receptor of the human Mas-related G-protein coupled receptor D (MRGPRD) in the regulation of the inflammatory mediator Consequently, the dynamic range for IL-6 detection as an assay for β-alanine-mediated activation of MRGPRD Overall, the observation that MRGPRD mediates the release of IL-6 in an in vitro system, hints at a role as an inflammatory mediator and supports the notion that IL-6 can be used as a marker for MRGPRD activation

Sandra Berndt talk about new structural perspectives in GPCR-mediated Src family kinase activation.

pharmacological activation of endogenous Ca2+ signaling transducers; however, such approaches can lack specificity This study demonstrated Gαq-G-protein coupled receptor (GPCR)-mediated [Ca2+]i signaling involvement cartilage-like matrix production, and it established hM3Dq as a powerful tool for elucidating the role of GPCR-mediated

The hepatitis B virus X protein (HBx) is involved in the process of hepatocellular carcinoma via the activation of various oncogenes. Our previous study indicated that ARBB1 (arrestin beta 1) promotes hepatocellular carcinogenesis (HCC). However, the role of ARRB1 in HBx-related HCC remains unclear. Herein, we identified that ARRB1 was upregulated by HBx in vivo and in vitro. Arrb1 deficiency suppressed HBx-induced hepatocellular carcinogenesis in several mouse models. Furthermore, knockdown of ARRB1 blocked HBx-induced macroautophagic/autophagic flux and disrupted the formation of autophagosomes. ARRB1 interacted with HBx, and the autophagic core protein MAP1LC3/LC3, a scaffolding protein, was essential for complete autophagy. Inhibition of autophagy by 3-methyladenine or interference of ATG5 or ATG7 attenuated HBx-induced cell cycle acceleration and the subsequent proliferative response via the induction of G1/S arrest. The absence of autophagy abolished the phosphorylation of CDK2 and the activity of the CDK2-CCNE1 complex. Our results demonstrate that ARRB1 plays a critical role in HBV-related HCC via modulating autophagy and the CDKN1B-CDK2-CCNE1-E2F1 axis and indicate that ARRB1 may be a potential therapeutic target for HCC. Abbreviations: ARRB1: arrestin beta 1; ACTB: actin beta; AMPK: adenosine monophosphate (AMP)-activated protein kinase; ATG5: autophagy related 5; ATG7: autophagy related 7; Baf A1: bafilomycin A1; CDK2: cyclin dependent kinase 2; CDKN1B/p27Kip1: cyclin dependent kinase inhibitor 1B; CQ: chloroquine; E2F1: E2F transcription factor 1; FBS: fetal bovine serum; GPCRs: G protein-coupled receptors; GST: glutathione S-transferase; HCC: hepatocellular carcinoma; HBV: hepatitis B virus; HBx: hepatitis B virus X protein; HMGB1: high mobility group box 1; HIF1A/HIF-1α: hypoxia inducible factor 1 subunit alpha; IHC: immunohistochemistry; JAK1: Janus kinase 1; LOX: lysyl oxidase; MAP1LC3B/LC3: microtubule associated protein 1 light chain 3 beta; MKI67: marker of proliferation Ki-67; MTOR: mechanistic target of rapamycin kinase; MAPK: mitogen-activated protein kinase; 3-MA: 3-methyladenine; NFKB/NF-κB: nuclear factor kappa B; PIK3CA: phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; PHHs: primary human hepatocytes; RB1: RB transcriptional corepressor 1; SQSTM1/p62: sequestosome 1; STAT: signal transducer and activator of transcription; TACR1/NK1R: tachykinin receptor 1. Read full article

October 2022 "Melanocortin 3 receptor (MC3R) is a G-protein coupled receptor (GPCR) that is defined as a regulator of appetite/hunger balance mechanisms mostly up to date. In addition to its function about weight gain and appetite control mechanisms of MC3R, recent studies showed that MC3R controls growth, puberty, and circadian rhythms as well. Despite the drastic effects of the MC3R deficiency in humans and other mammals, its cellular mechanisms are still under investigation. In this review paper, we aimed to point out the importance of the MC3R regulations in three main concepts: 1) its impact on weight and appetite control, 2) the control of growth, puberty, and circadian rhythm, and, 3) its protein-protein interactions and cellular mechanisms." Read more at the source #DrGPCR #GPCR #IndustryNews

Striatal mGlu5-mediated synaptic plasticity is independently regulated by location-specific receptor Specialized Pro-resolving Lipid Mediators and Resolution of Viral Diseases.

diversity of location, effectors, and signaling of GPCRs, and how these could interact to generate specific

Integration and Spatial Organization of Signaling by G Protein-Coupled Receptor Homo- and Heterodimer

October 2022 Keratinocyte-derived defensins activate neutrophil-specific receptors Mrgpra2a/b to prevent This signaling axis was required for effective neutrophil-mediated skin immunity and microbiome homeostasis animals both exhibited skin dysbiosis, with reduced microbial diversity and expansion of Staphylococcus species

Ligand-directed biased agonism at human histamine H3 receptor isoforms across Gαi/o- and β-arrestin2-mediated Emerging Voices in GPCR Biology in Special Issue of Molecular Pharmacology GPCR Events, Meetings, and Webinars October 17, 2024 | Unprecedented fragment-based screening using Spectral Shift for GPCRs October Ligand-directed biased agonism at human histamine H3 receptor isoforms across Gαi/o- and β-arrestin2-mediated recognition and activation of somatostatin receptors SSTR1 and SSTR3 SPMs exert anti-inflammatory and pro-resolving

Modulating a single function of a specific aGPCR isoform while affecting no other function and no other engineered an antibody, termed LK30, that binds to the extracellular region of the aGPCR ADGRL3, and specifically In cellular-adhesion assays, LK30 specifically broke the trans-cellular interaction of ADGRL3 with teneurin Our work provides proof of concept for the modulation of isoform- and ligand specific aGPCR functions

September 2022 Cell-Type-Specific Effects of the Ovarian Cancer G-Protein Coupled Receptor (OGR1) on roles of extracellular pH in the progression of pulmonary fibrosis, we sought to identify whether pH mediates

TRPM3 expression patterns differ between species and change during development.

Besides, ligand-specific subtle differences in the conformations assumed by intracellular loop 2 and

Sara Marsango and Graeme Milligan for their research on the Regulation of the pro-inflammatory G protein-coupled A special episode with our board, meet Drs. Maria Waldhoer, JoAnn Trejo, and Anne Marie Quinn. Candidate IDOR-1117-2520: A Potent and Selective Antagonist of CCR6 for Autoimmune Diseases MRGPRX4 mediates receptor family Technologies for the discovery of G protein-coupled receptor-targeting biologics Lipid mediators Exhibition June 2 - 7, 2024 | Chemotactic Cytokines June 9 - 14, 2024 | 2024 Phosphorylation and G-Protein Mediated

April is the month of DNA Day, a special day commemorating the discovery of the DNA double helix structure conformational changes that occur during G-protein activation by the β2-adrenergic receptor, using a time-resolved Time-resolved cryo-EM of G protein activation by a GPCR. bioRxiv : the preprint server for biology, 2023.03.20.533387

The more we know about the pathology of diseases, the more complicated it is to modulate them by a specific electrochemiluminescence, fluorescence emission, immunofluorescence staining, HTRF (homogeneous time-resolved fluorescence), and TR-FRET (time-resolved fluorescence resonance energy transfer). Signal-Regulated Kinase: A Regulator of Cell Growth, Inflammation, Chondrocyte and Bone Cell Receptor-Mediated Independent β-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular