the efficacy of seven agonists to induce G protein, G protein-coupled receptor kinase 2 (GRK2), as well

September 2022 "The follicle-stimulating hormone receptor (FSHR) belongs to the glycoprotein hormone receptors, a subfamily of G-protein-coupled receptors (GPCRs). FSHR is involved in reproductive processes such as gonadal development and maturation. Structurally, the extensive extracellular domain, which contains the hormone-binding site and is linked to the transmembrane domain by the hinge region (HR), is characteristic for these receptors. How this HR is involved in hormone binding and signal transduction is still an open question. We combined in vitro and in situ chemical crosslinking, disulfide pattern analysis, and mutation data with molecular modeling to generate experimentally driven full-length models. These models provide insights into the interface, important side-chain interactions, and activation mechanism. The interface indicates a strong involvement of the connecting loop. A major rearrangement of the HR seems implausible due to the tight arrangement and fixation by disulfide bonds. The models are expected to allow for testable hypotheses about signal transduction and drug development for GPHRs." Read more at the source #DrGPCR #GPCR #IndustryNews

Characterization of a new WHIM syndrome mutant reveals mechanistic differences in regulation of the chemokine receptor CXCR4 WHIM syndrome is a rare immunodeficiency disorder that is characterized by warts, hypogammaglobulinemia, infections, and myelokathexis. While several gain-of-function mutations that lead to C-terminal truncations, frame shifts and point mutations in the chemokine receptor CXCR4 have been identified in WHIM syndrome patients, the functional effect of these mutations are not fully understood. Here, we report on a new WHIM syndrome mutation that results in a frame shift within the codon for Ser339 (S339fs5) and compare the properties of S339fs5 with wild type CXCR4 and a previously identified WHIM syndrome mutant, R334X. The S339fs5 and R334X mutants exhibited significantly increased signaling compared to wild type CXCR4 including agonist-promoted calcium flux and extracellular signal-regulated kinase activation. This increase is at least partially due to a significant decrease in agonist-promoted phosphorylation, β-arrestin binding, and endocytosis of S339fs5 and R334X compared to wild type CXCR4. Interestingly, there were also significant differences in receptor degradation, with S339fs5 having a very high basal level of degradation compared to that of R334X and wild type CXCR4. In contrast to wild type CXCR4, both R334X and S339fs5 were largely insensitive to CXCL12-promoted degradation. Moreover, while basal and agonist-promoted degradation of wild type CXCR4 was effectively inhibited by the CXCR4 antagonist TE-14016, this had no effect on the degradation of the WHIM mutants. Taken together, these studies identify a new WHIM syndrome mutant, CXCR4-S339fs5, that promotes enhanced signaling, reduced phosphorylation, β-arrestin binding and endocytosis, and a very high basal rate of degradation that is not protected by antagonist treatment. Read full article

protein-coupled receptor kinase 2 is essential to enable vasoconstrictor-mediated arterial smooth muscle proliferation (VSMC) proliferation, contributing to the development of atherosclerotic plaques, re-stenosis lesions GPCR signalling through phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) promotes VSMC proliferation implicated in controlling various aspects of cellular growth, we examined whether GRK2 could affect VSMC proliferation These data suggest GRK2 expression is essential to facilitate vasoconstrictor-driven VSMC proliferation

August 2022 "GPCRs in Medicinal Chemistry Event 8th RSC / SCI symposium on GPCRs in Medicinal Chemistry Dates Wednesday-Friday, 5th-7th October 2022 Place Evotec Campus Levi-Montalcini, Verona, Italy Downloads and Links Registration closing dates: 6th September – registration against invoice (bank transfers): Tuesday, 6th September 30th September – online registration (card payments)" Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 RAB-Symposium - Regulatory Autoantibodies Targeting GPCRs. September 15-16, 2022. Lübeck, Germany. Hybrid meeting. "Dear Sir or Madam, dear Colleagues, It gives me great pleasure to announce the fourth hybrid symposium on regulatory autoantibodies targeting G-protein-coupled receptors (GPCRs) in Lübeck. GPCRs are involved in a variety of physiological and pathophysiological processes. So far, numerous therapeutics targeting GPCRs have been developed, with a focus on small molecules and monoclonal antibodies for the treatment of cancer, infections, metabolic disorders or inflammatory diseases. Recently, functional autoantibodies targeting GPCRs have been associated with various disease-specific manifestations, highlighting a potential new area for therapeutic intervention. Therefore, the aim of this symposium is to bring together the current knowledge on the role of autoantibodies targeting GPCRs in various diseases, such as cardiovascular diseases, renal diseases, autoimmune diseases such as systemic sclerosis or systemic lupus erythematosus. In addition, one aim is to bring together the mode of action of autoantibodies in immune regulation and pathogenesis." Read more at the source #DrGPCR #GPCR #IndustryNews

Discovery on Target (DOT) highlights advances in current and emerging “hot” targets and technologies, as well

August 2022 "WELCOME 4GPCRnet meeting bringing together four of the biggest GPCR networks in Europe for a joint meeting in Leipzig. Four of the biggest European networks on GPCR research (COST Actions Adher’n Rise and ERNEST plus DFG-funded SFB1423 and FOR2372) have joined forces to organize an international meeting, which will take place from 26th-29th September 2022 in the beautiful city of Leipzig in Germany. We aim to connect renowned international experts of the field with early career ‘rising stars’. The event will take place in the heart of Leipzig, which offers a colorful mixture of culture and vivid social life." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "We are happy to announce you our 2nd IRN i-GPCRnet meeting that will be held at the University of Wurzburg (Germany) from september 30th to october 1rst." Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 Bell-Evans model and steered molecular dynamics in uncovering the dissociation kinetics optimized approach of combining the data derived from steered molecular dynamics simulations and the Bell-Evans

the direct role of fentanyl on cancer, little is known on the effect of fentanyl on ovarian cancer cells Methods Proliferation, migration and apoptosis assays were performed in ovarian cancer cells after

signaling GPCR Binders, Drugs, and more Selenomethionine Promotes Milk Protein and Fat Synthesis and Proliferation of Mammary Epithelial Cells through the GPR37-mTOR-S6K1 Signaling GPCRs in Neuroscience Astrocyte Gi-GPCR Innovation Forum Nxera Pharma Notes Positive Phase 2 Data for Partnered Schizophrenia Candidate NBI-1117568 Call , 2024 | 4th Transatlantic ECI GPCR Symposium September 18, 2024 | FREE Webinar - The value of GPCR cell-based

March 2022 " Geneva, Switzerland, March 7, 2022 – Addex Therapeutics (SIX: ADXN, Nasdaq: ADXN), a clinical-stage pharmaceutical company pioneering allosteric modulation-based drug discovery and development, announced today that it will issue its full-year 2021 financial results on Thursday, March 10, 2022. Tim Dyer , CEO, Roger Mills , CMO and Robert Lütjens , Head of Discovery Biology, will provide a business update and review its pipeline during a teleconference and webcast for investors, analysts and media at 16:00 CET (15:00 GMT / 10:00 EST / 07:00 PST) the same day. " Read more at the source #DrGPCR #GPCR #IndustryNews

STING) signaling pathway has been implicated in organ injuries and its activation inhibits endothelial proliferation showed that cGAS expression was induced in fibrotic liver and kidney, but suppressed in endothelial cells Meanwhile, cGAS deletion upregulated profibrotic Yes-associated protein (YAP) signaling in endothelial cells

High expression of GPR50 promotes the proliferation, migration and autophagy of hepatocellular carcinoma cells in vitro. Gi/o GPCRs drive the formation of actin-rich tunneling nanotubes in cancer cells via a Gβγ/PKCα/FARP1 Comparative analysis of the occupancy of Histone H3 Lysine 4 methylation in the cells treated with TGFβ Autocrine proteinase-activated receptor signaling in PC3 prostate cancer cells.

neurological and psychiatric disorders: An in silico approach Opioid modulation of prefrontal cortex cells and circuits GPCRs in Oncology and Immunology RGS20 promotes non-small cell lung carcinoma proliferation Blockade of vasoactive intestinal peptide receptor 2 (VIPR2) signaling suppresses cyclin D1-dependent cell-cycle progression in MCF-7 cells Methods & Updates in GPCR Research Cryo-electron microscopy for GPCR research

transient receptor potential ankyrin subtype 1 protein (TRPA1) signaling pathways, thereby regulating proliferation Several recent studies have demonstrated that TGR5 exerts inconsistent effects in different cancer cells

immunohistochemistry approach The combination of brentuximab vedotin and chidamide synergistically suppresses the proliferation of T-cell lymphoma cells through the enhancement of apoptosis Methods & Updates in GPCR Research Modulating prediction using a protein language model Reviews, GPCRs, and more Potential of olfactory neuroepithelial cells

The immune system depends on chemokines to direct cell migration during immune surveillance and inflammation CCR2 is an example of a dual-function receptor that directly regulates both cell migration and scavenging Scavenging allows cells to continuously migrate by remaining responsive to chemokines, it dampens the , and CCR5 switch purely to scavenging (D'Amico G. et al. 2000), becoming incapable of promoting cell migration, a phenomenon which is likely to be mediated by changes in the cell motility machinery with

Submit a 1-minute abstract video and tell us more about your project using this form. GPCRs Dual role of the adhesion G-protein coupled receptor ADRGE5/CD97 in glioblastoma invasion and proliferation Intracellular calcium ion transients evoked by cell poking independently of released autocrine ATP in Madin-Darby canine kidney cells.

., 1950 ), also called Duffy-antigen/receptor for chemokines, or DARC ( Novitzky-Basso and Rot, 2012 Erythrocytes are terminally differentiated anuclear cells with no transcription and limited translation Additionally, ACKR1 expression characterizes venular endothelial cells (ECs) ( Pruenster et al., 2009 This well-established, distinctive pattern of cell expression has been directly challenged by a publication and ECs, suggesting that macrophage ACKR1 engages its non-cognate ligand CD82 on hematopoietic stem cells

non-canonical pathway GPCR Screening Reveals that the Metabolite Receptor HCAR3 Regulates Epithelial Proliferation regulates the expression and alternative splicing of genes associated with aphasia-related diseases in PC12 cells Scientist Senior Research Associate/Associate Scientist, Protein Science Post-Doctoral Fellow—Pharmacology/Cell

Front Cell Dev Biol, 2021. 9: p. 611443. 3.      ., Revealing the Activity of Trimeric G-proteins in Live Cells with a Versatile Biosensor Design.  Cell, 2020. 182(3): p. 770-785.e16. 4.      Galés, C., et al., Real-time monitoring of receptor and G-protein interactions in living cells.  Goyet, E., et al., Fast and high resolution single-cell BRET imaging. 

September 2022 "T cells are master regulators of the immune response tuning, among others, B cells, macrophages and NK cells. To exert their functions requiring high sensibility and specificity, T cells need to integrate different of the cytoskeleton and lipid microdomains in controlling signalling compartmentalization during T cell Here, we discuss mechanisms responsible for signalling amplification and compartmentalization in T cell

Congratulations to the GPCR Therapeutics team for their publication on improving hematopoietic stem cell Activation and Signaling The GPCR adaptor protein Norbin regulates S1PR1 trafficking and the morphology, cell cycle and survival of PC12 cells GLP-1 and GIP receptors signal through distinct β-arrestin 2-dependent pathways to regulate pancreatic β cell function GPCR Binders, Drugs, and more GPC-100, a novel CXCR4 antagonist, improves in vivo hematopoietic cell mobilization when combined with propranolol Discovery

understood in cardiomyocytes and vascular smooth muscle cells (VSMCs). In VSMCs, stimulation of GPCRs also modulates contractile and cell growth phenotypes. on key signaling events involved in the activation and differentiation of these cells. signaling events driving the fibrotic response and the communications between fibroblasts and other cells Finally, we explore what such connections between the cell surface and nuclear GPCR signaling might mean

GPCRs in Oncology and Immunology A2aR on lung adenocarcinoma cells: A novel target for cancer therapy Pharmacological inhibition of neuropeptide Y receptors Y1 and Y5 reduces hypoxic breast cancer migration, proliferation 15, 2023) GPCRs in drug discovery: challenges & solutions (June 19 - 23, 2023) Training School on “Cell-based

as in human melanoma cells either expressing (A7) or lacking (M2) FLNA. First, we observed the formation of endogenous SST5 homo-dimers in GH3, A7, and M2 cells. SST2 and SST5 can also form endogenous hetero-dimers in these cells. robust receptor internalization at shorter times than in A7 cells. In conclusion, we demonstrated that in GH3 cells SST2 and SST5 can form both homo- and hetero-dimers