September 2022 "The activation of phospholipase C (PLC) is thought to have a key role in the cardiomyocyte response to several different hypertrophic agents such as norepinephrine, angiotensin II and endothelin-1. PLC activity results in the generation of diacylglycerol and inositol trisphosphate, which are downstream signal transducers for the expression of fetal genes, increased protein synthesis, and subsequent cardiomyocyte growth. In this article, we describe the signal transduction elements that regulate PLC gene expression. The discussion is focused on the norepinephrine- α1-adrenoceptor signaling pathway and downstream signaling processes that mediate an upregulation of PLC isozyme gene expression. Evidence is also indicated to demonstrate that PLC activities self-regulate the expression of PLC isozymes with the suggestion that PLC activities may be part of a coordinated signaling process for the perpetuation of cardiac hypertrophy. Accordingly, from the information provided, it is plausible that specific PLC isozymes could be targeted for the mitigation of cardiac hypertrophy." Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 Regulation of pulmonary surfactant by the adhesion GPCR GPR116/ADGRF5 requires a tethered agonist-mediated activation mechanism "The mechanistic details of the tethered agonist mode of activation for the adhesion GPCR ADGRF5/GPR116 have not been completely deciphered. We set out to investigate the physiological importance of autocatalytic cleavage upstream of the agonistic peptide sequence, an event necessary for NTF displacement and subsequent receptor activation. To examine this hypothesis, we characterized tethered agonist-mediated activation of GPR116 in vitro and in vivo. A knock-in mouse expressing a non-cleavable GPR116 mutant phenocopies the pulmonary phenotype of GPR116 knock-out mice, demonstrating that tethered agonist-mediated receptor activation is indispensable for function in vivo. Using site-directed mutagenesis and species-swapping approaches, we identified key conserved amino acids for GPR116 activation in the tethered agonist sequence and in extracellular loops 2/3 (ECL2/3). We further highlight residues in transmembrane 7 (TM7) that mediate stronger signaling in mouse versus human GPR116 and recapitulate these findings in a model supporting tethered agonist:ECL2 interactions for GPR116 activation." Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 "Visual phototransduction is the most extensively studied G protein-coupled receptor (GPCR) signaling pathway because of its quantifiable stimulus, non-redundancy of genes, and immense importance in vision. We summarize recent discoveries that have advanced our understanding of rod outer segment (ROS) morphology and the pathological basis of retinal diseases. We have combined recently published cryo-electron tomography (cryo-ET) data on the ROS with structural knowledge on individual proteins to define the precise spatial limitations under which phototransduction occurs. Although hypothetical, the reconstruction of the rod phototransduction system highlights the potential roles of phosphodiesterase 6 (PDE6) and guanylate cyclases (GCs) in maintaining the spacing between ROS discs, suggesting a plausible mechanism by which intrinsic optical signals are generated in the retina." Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 "We describe production of the human A2A adenosine receptor (A2AAR), a class A G protein-coupled receptor (GPCR) for 19F-NMR and single-molecule fluorescence (SMF) spectroscopy. We explain in detail steps shared between the two sample preparation strategies, including expression and isolation of A2AAR and assembly of A2AAR in lipid nanodiscs and procedures for incorporation of either 19F-NMR or fluorescence probes. Protocols for SMF experiments include sample setup, data acquisition, data processing, and error analysis. For complete details on the use and execution of this protocol, please refer to Wei et al. (2022) and Sušac et al. (2018)." Read more at the source #DrGPCR #GPCR #IndustryNews

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

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

Structurally, the extensive extracellular domain, which contains the hormone-binding site and is linked

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

for disease therapy GPCRs in Cardiology, Endocrinology, and Taste Transcriptomic profiling highlights cell cells by targeting PAR-1 G protein-coupled receptors related to autoimmunity in postural orthostatic of the nematode-trapping fungus Arthrobotrys flagrans activates mitochondria and reprograms fungal cells for nematode hunting Role and recent progress of P2Y12 receptor in cancer development Mutation Patterns immunotherapy: a Society for Immunotherapy of Cancer (SITC) strategic vision Structural and Molecular

have been developed, with a focus on small molecules and monoclonal antibodies for the treatment of cancer

In various pathological conditions, including cancer, aberrant ERK activity can lead to uncontrolled Cell Receptor-Mediated Gene Expression. ERK: a double-edged sword in cancer. ERK-dependent apoptosis as a potential therapeutic strategy for cancer. Cells, 10(10), 2509. Biology of the Cell, 93(1‐2), 71-79. Wei, H., Ahn, S., Shenoy, S. K., Karnik, S.

I would like to take this opportunity to thank all our French partners who trust us in the generation #technology #lifescience #immunology #antibodies #medicine #cancer #innovation #gpcr #synabs #monoclonalantibodies

and infectious diseases (Proudfoot 2002), and in recent years attention has increasingly focused on cancer The involvement of chemokines and their receptors in several aspects of cancer biology, represents a inhibitor of the CCR5 used in HIV therapy; and the small molecule plerixafor, a CXCR4 antagonist used in cancer A lot of effort has been put forward to target CKRs especially in cancer, nevertheless, targeting this receptors redundancy and the fact that different chemokine receptors are overexpressed and promote cancer

ubiquitously expressed ORs, although there are highly increased in prostate tissue, especially in prostate cancer modulated by this tight mechanism with transcriptomic analysis revealing that while the majority of cancer and OR51E2, initially assumed to be GPCRs only expressed in prostate tissue, play a role in prostate cancer epithelial cells proliferation via activation by β-ionone which initiates prostate cancer cell cycle In non-small-cell lung cancer OR2J3 activation induced apoptosis and inhibited cell proliferation and

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 Esophageal and gastric cancer incidence trends in Golestan, Iran: An age-period-cohort analysis 2004 Autocrine proteinase-activated receptor signaling in PC3 prostate cancer cells. Multi-omics integration analysis of GPCRs in pan-cancer to uncover inter-omics relationships and potential

June 2022 "June 15, 2022 06:30 AM EDT - In 2016, Abbie Celniker was promoted to partner at Third Rock Ventures as the firm raised just over $600 million for its fourth fund. Since then, Celniker has helped usher in an additional fund and headed a few startups as interim CEO. Coming on its 15th year, Third Rock Ventures announced its sixth fund today — and largest one by far — at a whopping $1.1 billion. Adding it all up, Third Rock has raised $3.8 billion since its inception. That money has gone to some 60 biotechs, much of it as early funding." Read more at the source #DrGPCR #GPCR #IndustryNews

Vladimir Katanaev and colleagues identified compromised GPCR signaling in cancer cells using improved cells GPCRs in Neuroscience Neurotensin receptor 1-biased ligand attenuates neurotensin-mediated excitation activation PAXIP1-AS1 is associated with immune infiltration and predicts poor prognosis in ovarian cancer S1P1 signaling axis Methods & Updates in GPCR Research Magnetic Liposomes Infused with GPCR-Expressing Cell Sewage Optogenetic manipulation of Gq- and Gi/o-coupled receptor signaling in neurons and heart muscle cells

Direct Selection of DNA-Encoded Libraries for Biased Agonists of GPCRs on Live Cells. Bioorthogonal Tethering Enhances Drug Fragment Affinity for G Protein-Coupled Receptors in Live Cells Single-cell transcriptome analysis of NEUROG3+ cells during pancreatic endocrine differentiation with Small-molecule targeting of GPCR-independent noncanonical G-protein signaling in cancer. RGS proteins and their roles in cancer: friend or foe?.

discovered the vast potential for GPCR-targeting drugs in treating a range of health conditions, from cancer

macrophages in a quantitative systems pharmacology model of immunotherapy in triple-negative breast cancer It has begun to play important roles in drug development for complex diseases such as cancer, including triple-negative breast cancer (TNBC). nab-paclitaxel has shown clinical activity in advanced TNBC with PD-L1-positive tumor-infiltrating immune cells incorporated the dynamics of TAMs into our previously published QSP model to investigate their impact on cancer

The immune system depends on chemokines to direct cell migration during immune surveillance and inflammation in the chemokine system can also contribute to various diseases, such as inflammatory conditions and cancer 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

RGS4 is expressed in various immune cells, including T cells and B cells, and has been shown to modulate to T cell activation[6]. has been implicated in a range of diseases, including cardiovascular disease, pain, hypertension, and cancer While in cancer, RGS proteins are involved in regulating cell proliferation and survival[8]. al., Identification of a five-gene signature of the RGS gene family with prognostic value in ovarian cancer

interaction were conducted, confirming decreased homodimerization capacities of chimeric receptors in HEK293 cells In summary, our study shows that inhibiting homodimerization has a setmelanotide-like effect on Gq/11

On the other hand, RTKs play pivotal roles in growth factor signaling, regulating cell growth, differentiation , BRET, pull down, and transwell cell migration assays to investigate the effects of these modifications phosphorylation events highlights a nuanced regulatory mechanism that could be crucial in contexts such as cancer GPCR-dependent pathways by growth factor signaling might contribute to altered cellular behaviors in cancer , promoting uncontrolled cell migration and invasion.

ADGRB1/BAI1) Generated from an Alternative Promoter in Intron 17 The adhesion-GPCR ADGRF5 fuels breast cancer cells GPCRs in Oncology and Immunology Metabolic crosstalk: Extracellular ATP and the tumor microenvironment in cancer progression and therapy Agonists of galanin subtype 2 receptor may prevent pancreatic cancer and agonists of angiotensin II type 2 receptor may prevent colorectal cancer Distinct Activation Mechanisms radiopharma play   GPCR Events, Meetings, and Webinars September 18, 2024 | FREE Webinar - The value of GPCR cell-based

novel proteins for biology and health research Innovate UK announced the winners of its Transforming Cancer Therapeutics grant, which focuses on developing life-changing cancer treatments. Molecular Pharmacology - The Hauser Group NEW Postdoctoral Scholar – iPSC in cardiac and endothelial cell Class A GPCR-biased ligands GPCRs in Cardiology, Endocrinology, and Taste CRTC1 in Mc4r-expressing cells power of many: Multilevel targeting of representative chemokine and metabolite GPCRs in personalized cancer

Adam W Smith for their research on β2-adrenergic receptor associates with CXCR4 multimers in human cancer cells Dr. of dynamic cAMP responses to GPCR agonists for exploration of GLP-1R ligand effects in pancreatic β-cells GPCRs in Oncology and Immunology The β2-adrenergic receptor associates with CXCR4 multimers in human cancer Cancer Cells GPCR Events, Meetings, and Webinars April 1 - 4, 2024 | 19th Annual Drug Discovery Chemistry

The sheer complexity of the cell and the astonishing diversity of diseases are just two reasons why researchers For example, chemotherapy, a powerful standard approach to kill fast-growing cancer cells, has the drawback of causing damage to healthy cells in the process, leading to side effects that can include pain, nausea drug development approaches include a range of techniques leveraging structural biology, immunology, cell