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GPCR function has revealed new paradigms with increasingly complex models of receptor activation and signaling Spatial-temporal signaling of GPCRs and physiological functions; 2. The structural basis for GPCR activation of down-stream signaling and regulatory proteins; and 4.

It’s signal—once the model interprets it.

Integration and Spatial Organization of Signaling by G Protein-Coupled Receptor Homo- and Heterodimer Information flow from a source to a receiver becomes informative when the recipient can process the signal Information exchange and interpretation is essential in biology and understanding how cells integrate signals communication occurs mostly through neurotransmitters and hormones, and receptors are responsible for signal led to the hypothesis that their dimeric state can provide the framework for temporal coincidence in signaling

November 2022 Deciphering the signaling mechanisms of β-arrestin1 and β-arrestin2 in regulation of cancer which interact directly and indirectly with a wide number of cellular partners and mediate downstream signaling adaptor proteins that control the recruitment, activation, and scaffolding of numerous cytoplasmic signaling complexes and assist in G-protein receptor signaling, thus bringing them into close proximity. This review delivers a concise overview of the role of β-arrestins with a primary emphasis on the signaling

detection tools, to HTRF ligand optimization techniques that reduce background noise and amplify weak signals , GPCR signaling in metabolism, and future directions in biased ligand pharmacology. Target protected agonism:  Internalized MT2 signaling escapes AGRP antagonism—unlike α-MSH. Just the signals that move science. FAQ: Premium Membership 🔹 What’s included? Those acting on the right signals today will shape tomorrow’s breakthroughs—and avoid delays others won

September 2022 Signaling pathways activated by sea bass gonadotropin-inhibitory hormone peptides in COS Herein, we further elucidated the intracellular signaling pathways mediating in sea bass GnIH actions and the potential interactions with sea bass kisspeptin (Kiss) signaling. GnIH can interfere with kisspeptin actions by reducing its signaling. Our results provide additional evidence for the understanding of signaling pathways activated by GnIH

September 2022 Regulator of G Protein Signaling 20 Correlates with Long Intergenic Non-Coding RNA (lincRNAs Interestingly, RGS (Regulators of G protein signaling) proteins, which negatively regulate GPCR signaling cystadenocarcinoma: p = 0.048); (d) RGS20 was found to be significantly associated with some tumor-related signaling

Furthermore, in sPD models, the shortening of PC is accompanied by increased Sonic Hedgehog (SHH) signal Inhibiting overactive SHH signaling may be a potential neuroprotective therapy for sPD."

March 2022 ERNEST has established an Emergency Fund for Ukrainian researchers. "General Eligibility Researchers affiliated to any legal entity in Ukraine (for example, schools and universities, research centers, governmental institutions, or private companies) Deadlines Start of the project: now End of the project: 31 October 2022 SHORT-TERM SCIENTIFIC MISSIONS (STSM) We offer short-term scientific mission grants to Ukrainian researchers who have been recently displaced by the war, or those who can travel to institutions participating in ERNEST COST Action. The purpose of the STSM is to carry out a collaborative research project on topics relevant to the network. Our scientific perspective is broad, and we are happy to consider any research proposals from those in need." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "Genetically encoded fluorescent biosensors allow intracellular signaling dynamics to be FRET), and we have recently developed a simple approach for in vivo detection of FRET-based biosensor signals By combining fiber photometry with FRET-based biosensors, we were able to track GPCR-dependent signaling Recording from specific neuronal populations, we can quantify intracellular signaling while simultaneously

September 2022 Roles of Focal Adhesion Kinase PTK2 and Integrin αIIbβ3 Signaling in Collagen- and GPVI-Dependent Thrombus Formation under Shear "Glycoprotein (GP)VI and integrin αIIbβ3 are key signaling receptors The multiple downstream signaling pathways are still poorly understood. Peptides did not influence GPVI-induced aggregation and Ca2+ signaling in the absence of shear. This work thereby supports the role of PTK2 in integrin αIIbβ3 activation and signaling."

September 2022 GPR84 signaling promotes intestinal mucosal inflammation via enhancing NLRP3 inflammasome

protein-coupled receptor (GPCR) kinases (GRKs) and arrestins mediate GPCR desensitization, internalization, and signaling not proximal, phosphorylation of the chemokine receptor CXCR4 specifies βarrestin1 (βarr1)-dependent signaling not proximal, C-tail phosphorylation sites are required for recruitment of the adaptor protein STAM1 (signal-transducing adaptor molecule) to βarr1 and focal adhesion kinase phosphorylation but not extracellular signal-regulated this study provides evidence that distal C-tail phosphorylation sites specify GRK-βarrestin-mediated signaling

We obsess over target validation, signaling pathways, expression patterns, and disease relevance. of new chemical sources beyond natural agonist analogs Awareness of how GPCR allostery and biased signaling chemists learned early that modifying endogenous molecules — hormones, neurotransmitters, and metabolic signals Allostery and Biased Signaling Change the Game The most profound change in GPCR drug discovery is our (NAMs) — attenuate signaling Biased agonists  — favor one intracellular pathway over another These are

Although numerous signals are known to regulate synapses, it remains unclear which signaling mechanisms referred to as "SynTAMs" for synaptic targeting molecules, that enable localized perturbations of cAMP signaling In vivo, suppression of postsynaptic cAMP signaling in CA1 neurons prevented formation of both Schaffer-collateral Retrograde trans-synaptic rabies virus tracing revealed that postsynaptic cAMP signaling is required adhesion-GPCRs drive synapse formation and produce cAMP, we suggest that spatially restricted postsynaptic cAMP signals

G protein-coupled receptor interactions and modification of signalling involving the ghrelin receptor In all cases, the receptor interaction changes downstream signalling and the responses to receptor agonists This review discusses the signalling mechanisms of GHSR1a alone and in combination with other GPCRs,

Are you ready to truly understand how pharmacologists predict whole-body drug response from a single experiment?   Terry Kenakin’s newest foundational lesson in Terry's Corner  cuts straight to it:   Why models are vital for translating lab data into clinical forecasts The 4 types of pharmacologic models (and when to use each) The truth about linear models: useful or misleading? How the Mass Action Law underpins nearly every model Future of Receptor Theory: Linkage vs. Probability Models   This is practical drug development expertise from Terry’s 40+ years of experience.   Beyond the lessons, Terry's Corner  is your exclusive gateway. Ecosystem Premium Members: Look for significant savings on this and other resources in your weekly Dr. GPCR News.   Elevate your pharmacology expertise. Unlock "Pharmacologic Models" now

Arrestins regulate a wide range of signaling events, most notably when bound to active G protein-coupled modulates Fgr activity with a hallmark bell-shaped concentration-dependence, consistent with a role as a signaling

October 2022 Dual loss of regulator of G protein signaling 2 and 5 exacerbates ventricular myocyte arrhythmias and disrupts the fine-tuning of Gi/o signaling "Aims: Cardiac contractility, essential to maintaining proper cardiac output and circulation, is regulated by G protein-coupled receptor (GPCR) signaling. Previously, the absence of regulator of G protein signaling (RGS) 2 and 5, separately, was shown to cause Whether RGS2 and 5 redundantly control G protein signaling to maintain cardiovascular homeostasis is

correlate with three cholesterol molecules that play essential roles in conformation stabilization and signaling Thus, our data deepen the understanding of cholesterol modulation in GPCR (G protein-coupled receptor) signaling

potency — it hinges on where receptors actually are, how they internalize, and how tissues interpret signals Visualization tools redefine our understanding of signaling in intact metabolic tissues. Listen to the episode ➤ Quick Links Assess GPCR Biased Signaling of Agonist How GPCR Collaboration Built an Innovation Engine From Pipettes to Platforms: The Evolution of GPCR Research How GPCR Spatial Signaling Acting on the right signals today shapes tomorrow’s breakthroughs — and prevents delays others won’t

Lysophosphatidic Acid and Several Neurotransmitters Converge on Rho-Kinase 2 Signaling to Manage Motoneuron IME by TASK1 inhibition, stimulated ROCK2, and depressed background resting currents via Gαq/ROCK2 signaling

GPCRs share a common mechanism of action via the β-arrestin scaffolding signaling complexes, which not only serve to desensitize GPCRs by internalization, but also mediate multiple downstream signaling events As signaling via the GPCRs, β2-adrenergic receptor (β2AR), and metabotropic glutamate receptor 2 (mGluR2

achieved for 6 by treatment with 1 µM CAN1404 for 24 h, and a corresponding increase in FSH-induced signaling

August 2022 Dopamine D 1 receptor-mediated β-arrestin signaling: Insight from pharmacology, biology, behavior, and neurophysiology "The awareness of the potential importance of functional selectivity/biased signaling been to identify GPCR-selective ligands that have bias in G protein-dependent vs. β-arrestin related signaling important pharmacological, molecular, and cellular studies relevant to D1-mediated β-arrestin-related signaling translatability of cell and animal models to have more precise functional targeting to harness the value of this signaling

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

Intracellular calcium ([Ca2+]i) signaling is a critical regulator of chondrogenesis, chondrocyte differentiation Calcium (Ca2+) signaling is known to direct processes that govern chondrocyte gene expression, protein Control of chondrocyte/chondroprogenitor Ca2+ signaling has been attempted through mechanical and/or Synthetic signaling platforms permitting precise and selective Ca2+ signal transduction can improve dissection of the roles that [Ca2+]i signaling plays in chondrocyte behavior.

β-arrestin recruiting GPR84 agonists "In order to avoid a prolonged pro-inflammatory neutrophil response, signaling Among the family of GPCR kinases (GRKs) that regulate receptor phosphorylation and signaling termination

August 2022 "Background: Activation of signaling effectors by G-protein coupled receptors (GPCRs) depends Although studies have focused on the G-protein signaling state, the mechanism for β-arrestin signaling

Objective: The goal of this study was to determine the glucometabolic effects of acute activation of Gs signaling Results: Acute stimulation of GsD signaling in SKM impaired glucose tolerance in lean and obese mice The acute metabolic effects of UCN2 were not mediated by SKM Gs signaling. Conclusions: Selective activation of Gs signaling in SKM causes an acute increase in blood glucose levels