relationship between the concentration of two distinct pro-inflammatory stimuli, lipopolysaccharide and interferon Here we show that lipopolysaccharide and interferon gamma influence messenger RNA abundances of the microglial

September 2022 "The glucagon-like peptide-1 receptor (GLP-1R) plays a key role in metabolism and is an , indicating an immune regulatory role of GLP-1. The expressed GLP-1R was functional, as stimulation with a GLP-1R agonist triggered an increase in intracellular Analysis of CD4+ T cells activated under T helper (Th) 1, Th2, Th17 and regulatory T (Treg) cell differentiation Given the high induction of GLP-1R in human iTreg cells, we hypothesize that GLP-1R+ iTreg cells play

September 2022 Microbial Metabolites Orchestrate a Distinct Multi-Tiered Regulatory Network in the Intestinal

August 2022 RAB-Symposium - Regulatory Autoantibodies Targeting GPCRs. September 15-16, 2022. Sir or Madam, dear Colleagues, It gives me great pleasure to announce the fourth hybrid symposium on regulatory

We uncovered a novel neuroprotective mechanism involving interaction between neurotrophic factor-α1 ( Co-immunoprecipitation and pull-down assays confirmed interaction between NFα1/CPE and 5-HTR1E and 125I studies demonstrated saturable, high-affinity binding to 5-HTR1E in stably transfected HEK293 cells (Kd = 13.82 Treatment of 5-HTR1E stable cells with NF-α1/CPE increased pERK 1/2 and pCREB levels which prevented

September 2022 Expression pattern and clinical significance of beta 2-adrenergic receptor in oral squamous cell carcinoma: an emerging prognostic indicator and future therapeutic target " Purpose: Beta 2-Adrenergic Receptor (β2-AR) is significantly overexpressed in various types of malignancies, which is associated with the worst prognosis. However, the role of β2-AR in oral cancer is not well identified. The present study aimed at investigating the β2-AR gene expression and its significance in relation with the clinicopathological features and overall survival of oral squamous cell carcinoma (OSCC) patients. Methods: Immunohistochemistry, western blot and quantitative real-time PCR techniques were used to analyze β2-AR protein and mRNA levels in a total of 65 histopathologically confirmed OSCC tissues (case group) and 65 normal tissues (control group) from the oral cavity." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 Deciphering the signaling mechanisms of β-arrestin1 and β-arrestin2 in regulation of cancer cell cycle and metastasis "β-Arrestins are ubiquitously expressed intracellular proteins with many functions which interact directly and indirectly with a wide number of cellular partners and mediate downstream signaling. Originally, β-arrestins were identified for their contribution to GPCR desensitization to agonist-mediated activation, followed by receptor endocytosis and ubiquitylation. However, current investigations have now recognized that in addition to GPCR arresting (hence the name arrestin). β-Arrestins are 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. They have participated in various cellular processes such as cell proliferation, migration, apoptosis, and transcription via canonical and noncanonical pathways. Despite their significant recognition in several physiological processes, these activities are also involved in the onset and progression of various cancers. This review delivers a concise overview of the role of β-arrestins with a primary emphasis on the signaling processes which underlie the mechanism of β-arrestins in the onset of cancer. Understanding these processes has important implications for understanding the therapeutic intervention and treatment of cancer in the future." Read more at the source #DrGPCR #GPCR #IndustryNews

Mark your calendars because registration opens on July 18, 2024! These engaging online courses will take place every Thursday at 10 am EST. Dates:  October 3rd to 31st, 2024 Overview: This course continues with the basics learned in Course 1 Let’s dive into the   Classified GPCR News  from July 1 to 7, 2024 GPCR Activation and Signaling GPCR-MAPK Adhesion GPCR Workshop July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology 2026

September 2022 Endothelin-1 Stimulates PAI-1 Protein Expression via Dual Transactivation Pathway Dependent ROCK and Phosphorylation of Smad2L "In addition to the carboxy region, Smad2 transcription factor can induced by endothelin-1 (ET-1) in bovine aortic endothelial cells (BAECs). <br /><strong>Results:</strong> TGF (2 ng/ml), EGF (100 ng/ml) and ET-1 (100 nM) induced the phosphorylation Moreover, ET-1-increased protein expression of PAI-1 was decreased in the presence of bosentan (ET receptor

acting on the same receptor trigger distinct signaling pathways, leading to varied biological outcomes [1] β-arrestin recruitment, relative to GLP-1 [6]. , relative to GLP-1 [8-10].   References 1.          Kenakin, T. and A. ., Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1.  

Early bird registration ends on April 18th. Join our upcoming Dr. analysis for GPCR pharmacology, which will be held on Thursdays between May 9th and May 30th, 2024, from 10 am to 12 pm EDT. - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS Adhesion GPCR Workshop July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology 2026

You can submit your logo design by November 1st, and registration is unnecessary to participate. expression regulation by β2-adrenergic receptor Allosteric modulation of the fish taste receptor type 1 nasopharyngeal carcinoma Unbiased multitissue transcriptomic analysis reveals complex neuroendocrine regulatory Clinical Study of Oral GLP-1 Receptor Agonist GSBR-1290 and Provides Program Update Septerna sells GPCR , 2024 | AACR Annual Meeting May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET

Hello Dr. GPCR ecosystem members!  As Chief Matchmaker, I recently had the pleasure of speaking with Beth Fleck, Director of In Vitro Pharmacology at Crinetics Pharmaceuticals.  Beth is also the hiring manager for their open Principal Scientist, In Vitro Pharmacology role posted in the Dr. GPCR ecosystem.  Our conversation provided additional insight you cannot find in a job description, so I thought I’d share this insight with you. Mark:  “Beth, why did you decide to join Crinetics?” Beth:  “I was invited to join Crinetics a few years ago by some former colleagues and their description of the company was very intriguing: a biology focused, small molecule focused, smaller drug discovery company with a great work environment.  Crinetics hires people with big brains and small egos.” Mark:  “Have you found this to be accurate?” Beth:  “Yes.  There are a lot of learning opportunities at Crinetics.  We collaborate and cross-pollenate a lot.” Mark:  “So, what are the qualities of the perfect candidate for the Principal Scientist role?” Beth:  “We are looking for a thinker and problem solver who is able to learn.  Someone with strong assay development skills as well as strong data analysis and interpretation skills.” Mark:  “Are there particular assay types of interest?” Beth:  “We focus on biochemical, cell based, and radioligand binding assays to enable SAR, MOA, lead optimization, and new target discovery.  Top candidates will have a solid foundation in GPCR pharmacology as well as some experience in drug discovery.” Mark:  “Beth, why would someone want you as their boss?” Beth:  “Well, I enjoy training and mentoring team members.  I keep an open door and you’ll find me among the team in the lab quite often.  There’s comradery and open exchange in our team and I strive to provide learning opportunities for career development.” So, if you are looking for an on-site opportunity in San Diego and Beth’s comments sound good to you, please reach out to me at mschmeizl@grnwindsor.com or 860-325-3505 and we can dig a bit deeper. By: Mark Schmeizl Chief Matchmaker at Dr. GPCR

The cost is $299 and includes: All 4 live Zoom sessions ( 4x 1 hour lecture + 30 mins Q&A) 30-minute February 11 - 14, 2024 | 2024 BPS Annual Meeting March 5 - 7, 2024 | 3rd GPCRs - Targeted Drug Discovery Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference April 1 5 - 10, 2024 | AACR Annual Meeting April 22 - 23, 2024 | Endocrine Metabolic GPCRs May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS Europe 2024

Below is your Classified GPCR News at a glance for May 1 to 7, 2023. (May 14 - 19, 2023) PEGS Boston (May 15 - 19, 2023) 8th and final ERNEST Meeting in Crete. (June 10 - 11, 2023). (June 11 - 16, 2023). 1, 2023) 19th World Congress of Basic & Clinical Pharmacology 2023.

August 2022 "G-protein-coupled receptors (GPCRs) receive signals from ligands with different efficacies, and transduce to heterotrimeric G-proteins to generate different degrees of physiological responses. Previous studies revealed how ligands with different efficacies activate GPCRs. Here, we investigate how a GPCR activates G-proteins upon binding ligands with different efficacies. We report the cryo-EM structures of β1-adrenergic receptor (β1-AR) in complex with Gs (GαsGβ1Gγ2) and a partial agonist or a very weak partial agonist, and compare them to the β1-AR-Gs structure in complex with a full agonist. Analyses reveal similar overall complex architecture, with local conformational differences. Cellular functional studies with mutations of β1-AR residues show effects on the cellular signaling from β1-AR to the cAMP response initiated by the three different ligands, with residue-specific functional differences. Biochemical investigations uncover that the intermediate state complex comprising β1-AR and nucleotide-free Gs is more stable when binding a full agonist than a partial agonist. Molecular dynamics simulations support the local conformational flexibilities and different stabilities among the three complexes. These data provide insights into the ligand efficacy in the activation of GPCRs and G-proteins." Read more at the source #DrGPCR #GPCR #IndustryNews

Every Thursday at 10 AM EST: Principles of Pharmacology I October 3, 10, 17, 24 (four sessions) Explore Principles of Pharmacology II October 31, November 7, 14, 21, December 5 (five sessions) (we skipped Use discount code “ DRGPCR24 ” to save. 11th Adhesion GPCR Workshop    📍  Mexico City 📅 October 23- Adhesion GPCR Workshop November 5 - 7, 2024 | 16th Annual PEGS Europe   July 12 - 17, 2026 | 20th World Drosophila Kappa Opioid Receptor Activation Induces Epigenetic Silencing of Brain-Derived Neurotropic Factor

Using the parathyroid hormone type 1 receptor (PTHR) as a prototypic class B GPCR target, and a combination

Bursicon receptor gene HLGR2 as a potential RNA interference target for control of the fall webworm Hyphantria protein-coupled receptors (GPCRs) have been identified as a new generation of attractive targets for RNA interference

August 2022 "The cannabinoid CB1 receptor is the most abundant G protein coupled receptor (GPCR) in the central nervous system, which mediates the functional response to endocannabinoids and Cannabis compounds. A variety of ligands for CB1 receptors have been developed as promising drug candidates for the treatment of neurological disorders. New high-resolution structures of CB1 receptor in different functional states have significantly improved our molecular understanding of CB1 ligand interactions, selectivity, receptor activation and allosteric modulation. These advances have paved the way for development of novel ligands for different therapeutic applications. In this review, we describe the structural determinants for modulation of CB1 receptors by different types of ligands, as well as the differences between CB1 and its homologous, the CB2 receptor. LINKED ARTICLES: This article is part of a themed issue on Structure Guided Pharmacology of Membrane Proteins (BJP 75th Anniversary). " Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 Dopamine D 1 receptor-mediated β-arrestin signaling: Insight from pharmacology, biology,

September 2022 Angiotensin-(1-7) improves cognitive function and reduces inflammation in mice following Angiotensin 1-7 (Ang-1-7), an endogenous peptide, acts at the G protein coupled MAS1 receptors (MASR) Few studies have identified whether Ang-(1-7) decreases cognitive impairment following closed TBI. This study examined the therapeutic effect of Ang-(1-7) on secondary injury observed in a murine model

September 2022 Computational study of the conformational ensemble of CX3C chemokine receptor 1 (CX3CR1 ) and its interactions with antagonist and agonist ligands "The CX3C chemokine receptor 1 (CX3CR1), a

Latrophilin-1 drives neuron morphogenesis and shapes chemo- and mechanosensation-dependent behavior in Here, we show that Latrophilin-1 acts in trans to mediate morphogenesis of sensory structures in the Detailed expression and RNA-Seq analyses revealed specific LAT-1-positive neurons and first insights

; CQ: chloroquine; E2F1: E2F transcription factor 1; FBS: fetal bovine serum; GPCRs: G protein-coupled HIF1A/HIF-1α: hypoxia inducible factor 1 subunit alpha; IHC: immunohistochemistry; JAK1: Janus kinase 1; LOX: lysyl oxidase; MAP1LC3B/LC3: microtubule associated protein 1 light chain 3 beta; MKI67: marker rapamycin kinase; MAPK: mitogen-activated protein kinase; 3-MA: 3-methyladenine; NFKB/NF-κB: nuclear factor receptor 1.

due to mutations in the ANOS1 gene that encodes for the extracellular matrix (ECM) protein anosmin 1. We have previously shown interaction between PKR2 and anosmin 1 in vitro. In the current report we present evidence of the modulation of PK2/PKR2 activity by anosmin 1, since We also show that the N-terminal region of anosmin 1, capable of binding to the PK2-binding domain of (FnIII.1) suggest the cysteine-rich (CR) and the FnIII.1 domains could assist the WAP domain both in

September 2022 Biased GPCR signaling by the native parathyroid hormone-related protein 1 to 141 relative to its N-terminal fragment 1 to 36 "The parathyroid hormone (PTH)-related protein (PTHrP) is indispensable Although mature forms of PTHrP in the body consist of splice variants of 139, 141, and 173 amino acids endogenous PTHrP transduces signals through its cognate G-protein coupled receptor (GPCR), the PTH type 1 are caused by the stabilization of a singular PTHR conformation and PTHrP1-141 sensitivity to heparin

January 2022 Inversago Pharma Completes Phase 1 Clinical Trial on First-in-Class, Peripheral CB1 Blocker and Provides Strategy Update "Company has completed the Phase 1 Clinical Trial for its INV-202 molecule Encouraging Phase 1 results and supportive preclinical package assist in the launch of Phase 2 clinical Inversago”), the peripheral CB1 blockade company, announced today the successful completion of the Phase 1