Here, we show that human GPR125 likely undergoes cis-autoproteolysis when expressed in canine kidney The recruitment likely requires the C-terminal PDZ-domain-binding motif of GPR125 and its interaction

Chemical libraries containing fragment- (1.6 million molecules) and lead-like (4.6 million molecules) Among the top-ranked compounds, 59 fragments and 59 lead-like compounds were selected for experimental Of these, four fragment- and seven lead-like compounds were confirmed to bind to the allosteric site The results demonstrate that virtual screens of fragment- and lead-like chemical libraries have complementary

is the removal of the inhibitory GAIN domain and the dipping of the cleaved stalk peptide into the ligand-binding The structures reveal unique ligand-engaging mode, distinctive activation conformation, and key mechanisms

β-arrestin1 and 2 exhibit distinct phosphorylation-dependent conformations when coupling to the same GPCR in living

2022 "As the only member of the CX3C chemokine receptor subfamily, CX3CR1 binds to its sole endogenous ligand Here, we present two cryo-electron microscopy structures of CX3CR1-Gi1 complexes in ligand-free and CX3CL1

surgery is the cooperative improved action of the preproglucagon-derived hormones, glucagon, glucagon-like

and promotes expression of phosphoenolpyruvate carboxykinase 1 (PCK1), the enzyme catalyzing the rate-limiting

interaction of VLGR1 with key proteins of MAMs by pull-down assays in vitro complemented by in situ proximity ligation Immunocytochemistry by light and electron microscopy demonstrated the localization of VLGR1 in MAMs.

analyses indicated that the palmitoylation of Go can allosterically stabilize the critical residues in the ligand-binding pocket of GPR97 and increase the affinity of the ligand for GPR97.

the first receptors shown to transactivate other receptors: noticeably, these interactions are not limited

Pc(4-4), a lead backbone cyclic peptide, was selected out of a mini-library, directed toward PAR2&4 PH-binding AYPGKF peptide ligand activation of PAR4 induces EGF receptor (EGFR) Tyr-phosphorylation, effectively

structures of B2R have provided molecular insights into the functions and regulation of B2R, which shed light

However, most tools available to study the contribution of PKC isozymes have considerable limitations In this study, we generated and characterized human embryonic kidney 293A (HEK293A) cell lines devoid Our PKC KO cell lines expand the repertoire of KO HEK293A cell lines available to research GPCR pharmacology pharmacological tools to study PKC isozymes generally lack specificity and/or potency, we present the PKC KO cell lines

highlighted the most significant pathways associated with depression treatment, including neuroactive ligand-receptor targets (5-HTR, DR, ADRA, AR, ESR, NR3C1) and modulate the activation of multiple pathways (Neuroactive ligand

In rodents, intrathecal injection of its ligand, 7α,25-dihydroxycholesterol (7α,25-OHC), causes time-dependent

In this review, we provide an accessible summary of the literature on Alzheimer's disease and the therapeutic

We also showed that the EMC promotes surface expression of C3aR, likely explaining its identification

We generated mutant mouse lines lacking the entire Defensin (Def) gene cluster in keratinocytes or Mrgpra2a

Chemical libraries containing fragment- (1.6 million molecules) and lead-like (4.6 million molecules) Among the top-ranked compounds, 59 fragments and 59 lead-like compounds were selected for experimental Of these, four fragment- and seven lead-like compounds were confirmed to bind to the allosteric site The results demonstrate that virtual screens of fragment- and lead-like chemical libraries have complementary

assays were performed using PBMCs isolated from these individuals in response to the synthetic GPR15 ligand

presence of CaSR autoantibodies that operated as biased allosteric modulators of CaSR, and (g) were likely

unveiled a new antifibrotic cGAS/STING signaling pathway that suppresses pathological angiogenesis in liver We showed that cGAS expression was induced in fibrotic liver and kidney, but suppressed in endothelial cells. cGAS genetic deletion promoted liver and kidney fibrosis and pathological angiogenesis, including receptor (GPCR)-based antagonist that blocks the profibrotic activity of endothelial YAP, attenuated liver Further, pharmacological targeting of cGAS/STING-YAP axis exhibits the potential to alleviate liver and

Neural PKA signaling is regulated by afferent and peripheral efferent signals that link specific neural cell populations to the regulation of metabolic processes in adipose tissue, liver, pancreas, adrenal While limited, human studies infer differential regulation of the PKA system in obese compared to lean

October 2022 "Biased G protein-coupled receptor (GPCR) ligands, which preferentially activate G protein However, Gpr3-deficient mice display several adverse phenotypes, including elevated anxiety-like behavior by robust microglial and astrocytic hypertrophy, which suggest a protective glial response that may limit

October 2022 "Study of small molecule binding to live cells provides important information on the characterization of ligands pharmacologically. Here we developed and validated a label-free, liquid chromatography-mass spectrometry (LC-MS) based cell Competition binding analysis by titration of five known ligands suggested a good correlation with their This versatile method allows quantitative characterization of ligand binding to cell surface expressed

A diverse pharmacopoeia of cannabinoid ligands is available, which has led to considerable advancements However, until recently, most CB2 ligands were highly lipophilic and as such not optimal for clinical A number of strategies have been applied to develop CB2 ligands to achieve closer to 'drug-like' properties We review the current state of CB2 ligand development and progress in optimising physicochemical properties

October 2022 "Pepducins are small-lipidated peptides designed from the intracellular loops of G protein-coupled

protein-coupled receptors (GPCRs) activation assumes that stimulation of heterotrimeric G protein signaling upon ligand