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September 2022 β2-Adrenergic Receptor Expression and Intracellular Signaling in B Cells Are Highly Dynamic In the past, treatment of arthritic B cells with a β2-adrenergic receptor (β2-ADR) agonist has been shown In this study, the expression and signaling of β2-ADR in B cells during collagen-induced arthritis (CIA ) were investigated to provide an explanation of why only B cells from arthritic mice are able to improve Splenic B cells were isolated via magnetic-activated cell sorting (MACS).

October 2022 Keratinocyte-derived defensins activate neutrophil-specific receptors Mrgpra2a/b to prevent epithelial-cell-derived antimicrobial peptides defensins activated orphan G-protein-coupled receptors (GPCRs) Mrgpra2a/b generated mutant mouse lines lacking the entire Defensin (Def) gene cluster in keratinocytes or Mrgpra2a/b.

October 2022 Focusing on the role of secretin/adhesion (Class B) G protein-coupled receptors in placental Among them, the secretin/adhesion (Class B) G protein-coupled receptors are essential drug targets for Given the great value of the secretin/adhesion (Class B) G protein-coupled receptors in the regulation

class A G-protein coupled receptors (GPCRs) through a conserved binding site, not present in class B For class B GPCRs, previous molecular dynamics (MD) simulation studies have shown PI(4,5)P2 interacting appear to stabilize the inactive conformation of GCGR through a binding site conserved across class B This suggests differences in the regulatory function of PI(4,5)P2 between class A and class B GPCRs."

September 2022 "Serotonin receptor 5-HT2A and tropomyosin receptor kinase B (TrkB) strongly contribute

August 2022 "Abstract Rodent models are commonly used to evaluate parathyroid hormone (PTH) and PTH-related protein (PTHrP) ligands and analogues for their pharmacologic activities and potential therapeutic utility toward diseases of bone and mineral ion metabolism. Divergence, however, in the amino acid sequences of rodent and human PTH receptors (rat and mouse PTH1Rs are 91% identical to the human PTH1R) can lead to differences in receptor-binding and signaling potencies for such ligands when assessed on rodent vs human PTH1Rs, as shown by cell-based assays in vitro. This introduces an element of uncertainty in the accuracy of rodent models for performing such preclinical evaluations. To overcome this potential uncertainty, we used a homologous recombination-based knockin (KI) approach to generate a mouse (in-host strain C57Bl/6N) in which complementary DNA encoding the human PTH1R replaces a segment (exon 4) of the murine PTH1R gene so that the human and not the mouse PTH1R protein is expressed. Expression is directed by the endogenous mouse promoter and hence occurs in all biologically relevant cells and tissues and at appropriate levels. The resulting homozygous hPTH1R-KI (humanized) mice were healthy over at least 10 generations and showed functional responses to injected PTH analog peptides that are consistent with a fully functional human PTH1R in target bone and kidney cells. The initial evaluation of these mice and their potential utility for predicting behavior of PTH analogues in humans is reported here." Read more at the source #DrGPCR #GPCR #IndustryNews

The hepatitis B virus X protein (HBx) is involved in the process of hepatocellular carcinoma via the 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 kinase; MAPK: mitogen-activated protein kinase; 3-MA: 3-methyladenine; NFKB/NF-κB: nuclear factor kappa B;

October 2022 "Endogenous parathyroid hormone (PTH) and PTH-related peptide (PTHrP) bind to the parathyroid hormone receptor 1 (PTH1R) and activate the stimulatory G-protein (Gs) signaling pathway. Intriguingly, the two ligands have distinct signaling and physiological properties: PTH evokes prolonged Gs activation, whereas PTHrP evokes transient Gs activation with reduced bone-resorption effects. The distinct molecular actions are ascribed to the differences in ligand recognition and dissociation kinetics. Here, we report cryoelectron microscopic structures of six forms of the human PTH1R-Gs complex in the presence of PTH or PTHrP at resolutions of 2.8 -4.1 Å. A comparison of the PTH-bound and PTHrP-bound structures reveals distinct ligand-receptor interactions underlying the ligand affinity and selectivity. Furthermore, five distinct PTH-bound structures, combined with computational analyses, provide insights into the unique and complex process of ligand dissociation from the receptor and shed light on the distinct durations of signaling induced by PTH and PTHrP" Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 "Endogenous parathyroid hormone (PTH) and PTH-related peptide (PTHrP) bind to the parathyroid hormone receptor 1 (PTH1R) and activate the stimulatory G-protein (Gs) signaling pathway. Intriguingly, the two ligands have distinct signaling and physiological properties: PTH evokes prolonged Gs activation, whereas PTHrP evokes transient Gs activation with reduced bone-resorption effects. The distinct molecular actions are ascribed to the differences in ligand recognition and dissociation kinetics. Here, we report cryoelectron microscopic structures of six forms of the human PTH1R-Gs complex in the presence of PTH or PTHrP at resolutions of 2.8 -4.1 Å. A comparison of the PTH-bound and PTHrP-bound structures reveals distinct ligand-receptor interactions underlying the ligand affinity and selectivity. Furthermore, five distinct PTH-bound structures, combined with computational analyses, provide insights into the unique and complex process of ligand dissociation from the receptor and shed light on the distinct durations of signaling induced by PTH and PTHrP." Read more at the source #DrGPCR #GPCR #IndustryNews

Genome-wide identification of 216 G protein-coupled receptor (GPCR) genes from the marine water flea Here, we identified a total 216 full-length GPCR genes in the marine water flea Diaphanosoma celebensis genome, which were classified into five distinct classes (A, B, C, F, and other). D. celebensis to those in humans (Homo sapiens), fruitfly (Drosophila melanogaster), and freshwater water

October 2022 N-terminal alterations turn the gut hormone GLP-2 into an antagonist with gradual loss of

significant advantages in drug discovery, no single method can fully capture the impact of residue alterations Mutagenesis involves deliberately altering the DNA sequence of a gene to study the resulting changes J., Shoichet, B. K., & Jacobson, K. A. (2010). B., Chang, B., & Peisajovich, S. G. (2017). M., Marti-Solano, M., Sandhu, M., Kobilka, B. K., Bouvier, M., & Babu, M. M. (2023).

TM5 on one hand, and TM1 and TM7 on the other hand, form possible dimerization interfaces (Ploier, B. Li, et al 2012; B. Bai, et al. 2014; B. Ji, et al. 2020; L. Wan, 2020). Bai et al. 2014; B. Ji et al., 2020). that peptides derived from the transmembrane region of GPCRs can block the formation of dimers and alter example is a peptide derived from TM5/TM6 of the cannabinoid CB1 receptor (CB1R) which has been shown to alter

The possibility of dimerization in class A and class B GPCRs, however, has been more controversial, despite dimerization is critical for regulating GPCR function, particularly with respect to biased agonism, which may alter Graaf, C., et al., Glucagon-Like Peptide-1 and Its Class B G Protein-Coupled Receptors: A Long March Wootten, D., et al., Allostery and Biased Agonism at Class B G Protein-Coupled Receptors.  

Tagging molecules may alter the conformation or activity of GPCRs, leading to unintended effects on downstream B., & Diniz, C. (2021). D., & Collins, B. M. (2019). B., Gonçalves, J., & Diniz, C. (2019). B., Conti, M., & von Zastrow, M. (2017).

receptor activation and that the DRY motif plays a vital role in activating G-proteins and binding to B-arrestin4 A., Kobilka, B. K., Strader, D. J., Benovic, J. L., Dohlman, H. G., Frielle, T., Bolanowski, M. B. (2003). The G-protein-coupled receptors in the human genome form five main families. B., Panova, O., Hilger, D., Casiraghi, M., He, F., Maul, L., Gmeiner, P., Kobilka, B.

., Medel-Lacruz, B., Baidya, M., Makarova, M., Mistry, R., Goulding, J., Drube, J., Hoffmann, C., Owen 10), 2238–2255.e20. https://doi.org/10.1016/j.cell.2023.04.018 Janetzko, J., Kise, R., Barsi-Rhyne, B. C., von Zastrow, M., Inoue, A., & Kobilka, B. K. (2022). Classical and new roles of b-arrestins in the regulation of G-protein-coupled receptors. Nat. Rev. Molecular mechanism of b-arrestin-biased agonism at seven-transmembrane receptors. Annu. Rev.

References: Jin, B. K., Odongo, S., Radwanska, M., & Magez, S. (2023). journal of molecular sciences, 24(6), 5994. https://doi.org/10.3390/ijms24065994 Manglik, A., Kobilka, B. S., Devree, B. T., Rosenbaum, D. M., Thian, F. S., Kobilka, T. I., & Kobilka, B. K. (2011). C., Wess, J., & Kobilka, B. K. (2013).

A series of evidence shows that TGR5 induces protein kinase B (AKT), nuclear factor kappa-B (NF-κB),

The "herb-component-target" network indicated that the ingredients of Girinimbin, Gomisin B and Asarone In conclusion, this study preliminarily revealed key active components in KXS, including Gomisin B, Asarone

Class B G protein-coupled receptors (GPCRs) are notoriously difficult to target by small molecules because Using the parathyroid hormone type 1 receptor (PTHR) as a prototypic class B GPCR target, and a combination

GPCRs that internalize without arrestin have been classified as "class A" GPCRs whereas "class B" GPCRs

initiate a neuronal response that drives odorant discrimination and perception (Young J. and Trask B. elicit intracellular Ca2+flux in renal proximal tubule cells via adenylyl cyclase (AC) activity (Kalbe B and OR1D2 agonists, respectively, impact the contractility of human airway smooth muscle cells (Kalbe B. induced apoptosis and inhibited cell proliferation and migration in long-term stimulus experiments (Kalbe B.

announced it closed an oversubscribed $33 million financing round, extending its $100 million Series B

., Kobilka, B. K., Bouvier, M., & Babu, M. M. (2023). B., Mehrota, E., Grimes, P. R., ... & Manglik, A. (2024).

September 2022 "T cells are master regulators of the immune response tuning, among others, B cells, macrophages

Synaptamide suppressed osteoclastogenesis induced by receptor activator of nuclear factor-kappa B ligand

August 2022 "Oxysterols induce the migration of B-lymphocytes and dendritic cells to interfollicular