GPCR Activation and Signaling Cornichon protein CNIH4 is not essential for mice gametogenesis and fertility Revealing the tissue-level complexity of endogenous glucagon-like peptide-1 receptor expression and signaling Christopher Prior, as CEO and Reports Recent Drug Discovery Highlights Call for GPCR Papers GPCRs: Signal Transduction.

October 2022 "Psychedelics, also known as classical hallucinogens, affect processes related to perception, cognition and sensory processing mostly via the serotonin 5-HT2A receptor (5-HT2AR). This class of psychoactive substances, which includes lysergic acid diethylamide (LSD), psilocybin, mescaline and the substituted amphetamine 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), is receiving renewed attention for their potential therapeutic properties as it relates to psychiatric conditions such as depression and substance use disorders. Current studies focused on the potentially clinical effects of psychedelics on human subjects tend to exclude sex as a biological variable. Much of the understanding of psychedelic pharmacology is derived from rodent models, but most of this preclinical research has only focused on male mice. Here we tested the effects of DOI on head-twitch behavior (HTR) - a mouse behavioral proxy of human psychedelic potential - in male and female mice. DOI elicited more HTR in female as compared to male C57BL/6J mice, a sex-specific exacerbated behavior that was not observed in 129S6/SvEv animals. Volinanserin (or M100907) - a 5-HT2AR antagonist - fully prevented DOI-induced HTR in male and female C57BL/6J mice. Accumulation of inositol monophosphate (IP1) in the frontal cortex upon DOI administration showed no sex-related effect in C57BL/6J mice. However, the pharmacokinetic properties of DOI differed among sexes - brain and plasma concentrations of DOI were lower 30 and 60 min after drug administration in female as compared to male C57BL/6J mice. Together, these results suggest strain-dependent and sex-related differences in the behavioral and pharmacokinetic profiles of the 5-HT2AR agonist DOI in C57BL/6J mice, and support the importance of studying sex as a biological variable in preclinical psychedelic research." Read more at the source #DrGPCR #GPCR #IndustryNews

Let’s dive into the   Classified GPCR News  from July 22 to 28, 2024 GPCR Activation and Signaling Activating Inverse Regulation of C-C Chemokine Receptor 3 Oligomerization by Downstream Proteins Indicates Biased Signal Transduction Pathways Activation of a GPCR, ORL1 receptor: A novel therapy to prevent heart failure for diabetes treatment GPCRs in Neuroscience Astrocytes control quiescent NSC reactivation via GPCR signaling-mediated targets for ovarian cancer nanomedicines: from RNA sequencing data analysis to in vitro validation Signaling

GPCR Activation and Signaling Ubiquitylation of BBSome is required for ciliary assembly and signaling Unravelling GPCR signalling networks using global phosphoproteomics. arcoscreen is one of the 13 biotech companies to discover in western in 2023 Call for GPCR Papers GPCRs: Signal Transduction.

compounds with the highest affinities were demonstrated to be negative allosteric modulators of mGlu5 signaling

GPCR Activation and Signaling Targeting biased signaling by PAR1: Function and molecular mechanism of Loss of biased signaling at a G protein-coupled receptor in overexpressed systems. Call for GPCR Papers GPCRs: Signal Transduction. Ends tomorrow - March 31st, 2023. (June 28 - 30, 2023) FREE 11th Adrenoceptor Symposium: Adrenoceptors and GPCR Signalling (June 30 - July

GPCR Activation and Signaling Cell death signaling in Anopheles gambiae initiated by Bacillus thuringiensis Alkyl Chain of Δ9-Tetrahydrocannabinol GPCRs in Cardiology, Endocrinology, and Taste Cholecystokinin-A Signaling Oncology and Immunology From outside to inside and back again: the lysophosphatidic acid-CCN axis in signal transduction NPFF stimulates human ovarian cancer cell invasion by upregulating MMP-9 via ERK1/2 signaling , 2023 | Training Seminar "The Renaissance in GPCRs as Drug Targets: Allosteric Function and Biased Signaling

GPCR Activation and Signaling Autoregulation of GPCR signalling through the third intracellular loop. Approval for Change of Market Listing Segment to the Tokyo Stock Exchange Call for GPCR Papers GPCRs: Signal Transduction. (June 11 - 16, 2023). 11th Adrenoceptor Symposium: Adrenoceptors and GPCR Signalling (June 30 - July Integrated Approaches In Pharmacology, Computer Simulations And Machine Learning To Predict Ligand Signaling

GPCRs Functional partnerships between GPI-anchored proteins and adhesion GPCRs GPCR Activation and Signaling biased intracellular agonist The psychosis risk factor RBM12 encodes a novel repressor of GPCR/cAMP signal transduction The relaxin receptor RXFP1 signals through a mechanism of autoinhibition To probe the activation from inactive conformation using molecular dynamic simulations Kinetic insights into agonist-dependent signalling , 2023) Training Seminar "The Renaissance in GPCRs as Drug Targets: Allosteric Function and Biased Signaling

August 2022 "Emerging evidence suggests that G protein-coupled receptor (GPCR) kinases (GRKs) are associated with the pathophysiology of Alzheimer's disease (AD). However, GRKs have not been directly implicated in regulation of the amyloid-β (Aβ) pathogenic cascade in AD. Here, we determine that GRKs phosphorylate a non-canonical substrate, anterior pharynx-defective 1A (APH1A), an integral component of the γ-secretase complex. Significantly, we show that GRKs generate distinct phosphorylation barcodes in intracellular loop 2 (ICL2) and the C terminus of APH1A, which differentially regulate recruitment of the scaffolding protein β-arrestin 2 (βarr2) to APH1A and γ-secretase-mediated Aβ generation. Further molecular dynamics simulation studies reveal an interaction between the βarr2 finger loop domain and ICL2 and ICL3 of APH1A, similar to a GPCR-β-arrestin complex, which regulates γ-secretase activity. Collectively, these studies provide insight into the molecular and structural determinants of the APH1A-βarr2 interaction that critically regulate Aβ generation." Read more at the source #DrGPCR #GPCR #IndustryNews

Join us for the first virtual cafe talk to hear about the amazing work that Dr. Brian Arey is doing. https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe/ #gpcr #drgpcr #virtualcafe

We have previously reported that the MC4R forms homodimers, affecting receptor Gs signaling properties In this study, we analyzed effects of inhibiting homodimerization on Gq/11 signaling using previously Gq/11 signaling of chimeric receptors was analyzed using luciferase-based reporter gene (NFAT) assays Results demonstrate an improvement of alpha-MSH-induced NFAT signaling of chimeras, reaching the level of setmelanotide signaling at wild-type MC4R (MC4R-WT).

In Vitro Module Editing Of NRPS Enables Production Of Highly Potent Gq-Signaling Inhibitor FR900359 Adenosine A3 Receptor GPCRs in Cardiology, Endocrinology, and Taste Hepatic Regulator of G protein Signaling 14 Ameliorates NAFLD through Activating cAMP-AMPK Signaling by Targeting Giα1/3 APOL1-mediated monovalent cation transport contributes to APOL1-mediated podocytopathy in kidney disease Hepatocyte GPCR signaling transduction Structural and Molecular Insights into GPCR Function Segregation of nascent GPCRs in the

GPCR Activation and Signaling Components of TOR and MAP kinase signaling control chemotropism and pathogenicity A Rab10-ACAP1-Arf6 GTPases cascade modulates M4 muscarinic acetylcholine receptor trafficking and signaling Monitoring the Reversibility of GPCR Signaling by Combining Photochromic Ligands with Label-free Impedance Transduction. (June 28 - 30, 2023) 11th Adrenoceptor Symposium: Adrenoceptors and GPCR Signalling (June 30 - July 1

GPCR Activation and Signaling Coupling between GPR143 and dopamine D2 receptor is required for selective All-Atom Molecular Dynamics Simulations Indicated the Involvement of a Conserved Polar Signaling Channel Impact of membrane lipid polyunsaturation on dopamine D2 receptor ligand binding and signaling GPCR Binders Small-molecule targeting of GPCR-independent non-canonical G protein signaling inhibits cancer progression Transduction.

relationship between the conformational change of the receptor because of the mutation and related downstream signaling understanding of the relationship between the changed conformation of the receptor and consequently activated signaling

Biosciences won Top Out-Licensing Deal on the 8th annual Japan Deal of the Year Call for GPCR Papers GPCRs: Signal Transduction. (June 11 - 16, 2023). 11th Adrenoceptor Symposium: Adrenoceptors and GPCR Signalling (June 30 - July Integrated Approaches In Pharmacology, Computer Simulations And Machine Learning To Predict Ligand Signaling

October 2022 Intermolecular Interactions in G Protein-Coupled Receptor Allosteric Sites at the Membrane Interface from Molecular Dynamics Simulations and Quantum Chemical Calculations "Allosteric modulators are called promising candidates in G protein-coupled receptor (GPCR) drug development by displaying subtype selectivity and more specific receptor modulation. Among the allosteric sites known to date, cavities at the receptor-lipid interface represent an uncharacteristic binding location that raises many questions about the ligand interactions and stability, the binding site structure, and how all of these are affected by lipid molecules. In this work, we analyze interactions in the allosteric sites of the PAR2, C5aR1, and GCGR receptors in three lipid compositions using molecular dynamics simulations. In addition, we performed quantum chemical calculations involving the symmetry-adapted perturbation theory (SAPT) and the natural population analysis to quantify the strength of intermolecular interactions. We show that besides classical hydrogen bonds, weak polar interactions such as O-HC, O-Br, and long-range electrostatics with the backbone amides contribute to the stability of allosteric modulators at the receptor-lipid interface. The allosteric cavities are detectable in various membrane compositions. The availability of polar atoms for interactions in such cavities can be assessed by water molecules from simulations. Although ligand-lipid interactions are weak, lipid tails play a role in ligand binding pose stability and the size of allosteric cavities. We discuss physicochemical aspects of ligand binding at the receptor-lipid interface and suggest a compound library enriched by weak donor groups for ligand search in such sites." Read more at the source #DrGPCR #GPCR #IndustryNews

The S339fs5 and R334X mutants exhibited significantly increased signaling compared to wild type CXCR4 including agonist-promoted calcium flux and extracellular signal-regulated kinase activation. together, these studies identify a new WHIM syndrome mutant, CXCR4-S339fs5, that promotes enhanced signaling

focus on the relatively less well-studied effects of GPCRs in cardiac fibroblasts, focusing on key signaling We also review the hierarchy of signaling events driving the fibrotic response and the communications We discuss how such events may be distinct depending on where the GPCRs and their associated signaling Finally, we explore what such connections between the cell surface and nuclear GPCR signaling might mean

activity by anosmin 1, since this protein is able to enhance the activation of the ERK1/2 (extracellular signal-regulated

GPCR Activation and Signaling Transactivation of receptor tyrosine kinases by purinergic P2Y and adenosine GPCRs in Neuroscience Role of G-Proteins and GPCR-Mediated Signalling in Neuropathophysiology. Functional Assessment of Cancer-Linked Mutations in Sensitive Regions of Regulators of G Protein Signaling Ghrelin receptor signaling in health and disease: a biased view. Transduction.

in the role of GPCRs in lifespan are those that mimic dietary restriction, those related to insulin signaling

September 2022 Isoforms of GPR35 have distinct extracellular N-termini that allosterically modify receptor-transducer bias "Within the intestine, the human G protein-coupled receptor (GPCR) GPR35 is involved in oncogenic signaling cells to thoroughly profile both GPR35 isoforms for constitutive and ligand-induced activation and signaling provide clues for the future design of isoform-specific GPR35 ligands that selectively modulate GPR35-transducer

We discuss ligand binding, signaling, and structures of the vGPCRs in light of robust differences from

GPCR Activation and Signaling The dual-function chemokine receptor CCR2 drives migration and chemokine Platelet P2Y1 receptor exhibits constitutive G protein signaling and β-arrestin 2 recruitment. Simultaneous activation of CXC chemokine receptor 4 and histamine receptor H1 enhances calcium signaling Non-canonical Golgi-compartmentalized Gβγ signaling: mechanisms, functions, and therapeutic targets. Transduction.

2022 "Heterotrimeric G proteins couple activated G protein-coupled receptors (GPCR) to intracellular signaling of GPCR activation upon acquiring mutations that prevent GTPase activity and result in constitutive signaling YM-254890 (YM) can inhibit signaling by both GPCR-activated wild type αq and GPCR-independent αqQ209L Treatment of cells with YM failed to inhibit signaling by these PM-restricted αqQ209L. GPCR-dependent signaling by PM-restricted wild type αq is strongly inhibited by YM, demonstrating that

monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS)-stimulator of interferon genes (STING) signaling This study unveiled a new antifibrotic cGAS/STING signaling pathway that suppresses pathological angiogenesis Meanwhile, cGAS deletion upregulated profibrotic Yes-associated protein (YAP) signaling in endothelial Pharmacological targeting of cGAS/STING-YAP signaling by both a small-molecule STING agonist, SR-717, Together, our data support that activation of cGAS/STING signaling mitigates organ fibrosis and suppresses