September 2022 Microbial Metabolites Orchestrate a Distinct Multi-Tiered Regulatory Network in the Intestinal Epithelium That Directs P-Glycoprotein Expression "P-glycoprotein (P-gp) is a key component of the intestinal epithelium playing a pivotal role in removal of toxins and efflux of endocannabinoids to prevent excessive inflammation and sustain homeostasis. Recent studies revealed butyrate and secondary bile acids, produced by the intestinal microbiome, potentiate the induction of functional P-gp expression. We now aim to determine the molecular mechanism by which this functional microbiome output regulates P-gp. RNA sequencing of intestinal epithelial cells responding to butyrate and secondary bile acids in combination discovered a unique transcriptional program involving multiple pathways that converge on P-gp induction. Using shRNA knockdown and CRISPR/Cas9 knockout cell lines, as well as mouse models, we confirmed the RNA sequencing findings and discovered a role for intestinal HNF4α in P-gp regulation. These findings shed light on a sophisticated signaling network directed by intestinal microbial metabolites that orchestrate P-gp expression and highlight unappreciated connections between multiple pathways linked to colonic health." Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 Isoforms of GPR35 have distinct extracellular N-termini that allosterically modify receptor-transducer coupling and mediate intracellular pathway bias "Within the intestine, the human G protein-coupled receptor activation and signaling of 10 different heterotrimeric G proteins, ligand-induced arrestin recruitment, and receptor results reveal that the extended N-terminus of the long isoform limits G protein activation yet elevates receptor-β-arrestin contributed by the extended N-terminus of the long GPR35 isoform limits the extent of agonist-induced receptor-β-arrestin2

G protein-coupled receptors (GPCRs) are a vast family of membrane-bound proteins crucial for transmitting These receptors typically engage specific G protein subtypes, such as Gs, Gi/o, Gq/11, and G12/13, at receptor-mediated cAMP signalling, while Gs proteins similarly enhanced Gq dependent-vasopressin receptor-mediated receptors (β2AR) [4]. Stallaert, W., et al., Purinergic Receptor Transactivation by the β(2)-Adrenergic Receptor Increases

, essential to maintaining proper cardiac output and circulation, is regulated by G protein-coupled receptor

October 2022 "G protein-coupled receptors (GPCRs) are important drug targets characterized by a canonical impact of binding of agonists and antagonist/inverse agonists to selected structures of cannabinoid receptor 1 (CB1R), β2 adrenergic receptor (β2 AR) and A2A adenosine receptor (A2A AR). " Read more at the source

Previously, we identified potent positive crosstalk between insulin/IGF-1 receptors and G protein-coupled

Kathleen M Caron and her team studied the GPER/GPR30 complex with β1-adrenergic receptor and AKAP5 in January 8th to 14th, 2024 Adhesion GPCRs Conformational transitions and activation of the adhesion receptor CD97 GPCR Activation and Signaling Biased Signaling in Mutated Variants of β2-Adrenergic Receptor: Insights receptors in auditory neurons GPCRs in Oncology and Immunology G protein-coupled estrogen receptor ( GPER)/GPR30 forms a complex with the β1-adrenergic receptor, a membrane-associated guanylate kinase (

2022 N-terminal alterations turn the gut hormone GLP-2 into an antagonist with gradual loss of GLP-2 receptor selectivity towards more GLP-1 receptor interaction "Background and purpose: To fully elucidate the regulatory role of the GLP-2 system in the gut and the bones, potent and selective GLP-2 receptor (GLP To examine selectivity, COS-7 cells expressing human GLP-1 or GIP receptors were assessed for cAMP accumulation

on the mechanism of signal activation, ligand selectivity and allosteric modulation in angiotensin receptors Thus, we need to know much more about the structures of receptor-ligand complexes at high resolution. Recently, X-ray structures of both AngII receptors (AT1 and AT2 receptors) bound to peptide and non-peptide , as the basis of ligand selectivity, efficacy, and regulation of the molecular functions of the receptors This review covers the new data elucidating the structural dynamics of AngII receptors and how structural

pro-inflammatory neutrophil response, signaling downstream of an agonist-activated G protein-coupled receptor Among the family of GPCR kinases (GRKs) that regulate receptor phosphorylation and signaling termination The medium chain fatty acid receptor GPR84 as well as formyl peptide receptor 2 (FPR2), receptors expressed

Rho1 signaling is activated by G-protein-coupled receptor (GPCR) signaling at the cell surface. The SG receptor that transduces the Fog signal into Rho1-dependent myosin activation has not been identified

Genomics, in turn, played a crucial role in the discovery and sequencing of the beta-adrenergic receptor Another significant impact of genomics on GPCR research is the elucidation of receptor structure and receptor, using a time-resolved approach5. Cloning of the gene and cDNA for mammalian beta-adrenergic receptor and homology with rhodopsin. The G-protein-coupled receptors in the human genome form five main families.

Bioorthogonal Tethering Enhances Drug Fragment Affinity for G Protein-Coupled Receptors in Live Cells Differential Responses of the GLP-1 and GLP-2 Receptors to N-Terminal Modification of a Dual Agonist. Therapeutic antagonism of the neurokinin 1 receptor in endosomes provides sustained pain relief. Structural genomics of the human dopamine receptor system Structural Insights into Molecular Recognition and Receptor Activation in Chemokine–Chemokine Receptor Complexes Industry News Mavorixafor reduces

August 2022 "Emerging evidence suggests that G protein-coupled receptor (GPCR) kinases (GRKs) are associated

October 2022 "Protease-activated receptor 2 (PAR2) is a G-protein-coupled receptor (GPCR) activated by Interestingly, unlike PAR2-AP, GB83 and trypsin induced sustained receptor endocytosis and PAR2 colocalization

Consider G-protein-coupled receptors-an expansive class of transmembrane signaling proteins that participate While early evidence for the role of oligomerization in receptor signaling came from ensemble biochemical for these techniques to advance our understanding of the role of oligomerization in G-protein-coupled receptor

Considering the central role of the serotonin 5-HT2A receptor in the distinct effects of psychedelics

September 2022 "G-protein-coupled receptors (GPCRs) are involved in a wide array of physiological and Here, we find that protease-activated receptor 4 (PAR4) unexpectedly acts as a potent oncogene, inducing

CRAC Motif in Transmembrane Helix 2 Confers Cholesterol-Induced Thermal Stability to the Serotonin 1A Receptor "G protein-coupled receptors (GPCRs) constitute the largest class of membrane proteins that transduce The serotonin1A receptor is a crucial neurotransmitter receptor in the GPCR family involved in a multitude In addition, we showed that membrane cholesterol stabilizes the serotonin1A receptor against thermal consensus (CRAC) motif in transmembrane helix 2 in conferring the thermal stability of the serotonin1A receptor

September 2022 Fentanyl activates ovarian cancer and alleviates chemotherapy-induced toxicity via opioid receptor-dependent

October 2022 "Over three decades of research have provided thorough insights into G protein-coupled receptor Agonist activation of the β2-adrenoceptor (β2AR) causes its S-nitrosylation that is required for the receptor

Acquired hypocalciuric hypercalcemia (AHH) is a rare disease caused by calcium-sensing receptor (CaSR

been use for GPCR research are: Nb80: This nanobody stabilized an active-state conformation of the β2 adrenergic receptor (β2AR)3. receptor in a ground-state-like. Nanobodies to Study G Protein-Coupled Receptor Structure and Function. Activation and allosteric modulation of a muscarinic acetylcholine receptor.

Myocardium of Rats After an Acute Myocardial Infarction by Activating β-Arrestin-2, Protein Phosphatase 2A well as protein levels of Wnt1, phospho-Akt, transforming growth factor (TGF-β1), Smad, phospho-Smad3, α-SMA phosphorylation of Smad-3 and subsequent nuclear translocation to activate the transcription of collage 1/III and α-smooth muscle actin (α-SMA). Exendin-4, and possibly through G protein-coupled receptors (GPCRs), increases levels of cAMP and upregulates

Methods: To address this question, we studied mice that express a Gs-coupled designer G protein-coupled receptor receptor and CRF2 receptor) and studied the acute metabolic effects of activating these receptors in The acute metabolic effects following agonist activation of β2-adrenergic and, potentially, CRF2 receptors However, acute in vivo stimulation of endogenous Gs-coupled receptors enriched in SKM has only a limited impact on whole-body glucose homeostasis, most likely due to the fact that these receptors are also

intracellular allosteric binding site (IABS) has recently been identified at several G protein-coupled receptors Starting from vercirnon, an intracellular C-C chemokine receptor type 9 (CCR9) antagonist and previous

Silvio Gutkind, and team found that Gαs is essential for GRK selectivity and gene regulation by β2-adrenergic receptor. Matthew Eddy and lab research on GPCR signaling mechanisms using NMR spectroscopy with labeled receptors receptor Allosteric modulation of the fish taste receptor type 1 (T1R) family by the extracellular chloride ion Illuminating GPCR signaling mechanisms by NMR spectroscopy with stable-isotope labeled receptors

August 2022 "The apelin receptor (APJ) is a target for cardiovascular indications.