characterize nanobodies as tools for biochemical and structural studies of class IB phosphoinositide 3-kinases One of the most important signaling pathways in higher eukaryotes is the phosphoinositide 3-kinase (PI3K We identify nanobodies that stimulated lipid kinase activity, block Ras activation, and specifically

October 2022 Coincident Regulation of PLCβ Signaling by Gq-Coupled and μOpioid Receptors Opposes Opioid- Mediated Antinociception "Pain management is a significant problem worldwide. The current frontline approach for pain-management is the use of opioid analgesics. The primary analgesic target of opioids is the μ-opioid receptor (MOR). Deletion of phospholipase Cβ3 (PLCβ3), or selective inhibition of Gβγ regulation of PLCβ3, enhances the potency of the antinociceptive effects of morphine suggesting a novel strategy for achieving opioid sparing effects. Here we investigated a potential mechanism for regulation of PLC signaling downstream of MOR in HEK293 cells and found that MOR alone could not stimulate PLC, but rather required a coincident signal from a Gq coupled receptor. Knockout of PLCβ3, or pharmacological inhibition of its upstream regulators, Gβγ or Gq, ex vivo in periaqueductal gray (PAG) slices increased the potency of the selective MOR agonist DAMGO in inhibiting presynaptic GABA release. Finally, inhibition of Gq-GPCR coupling in mice enhanced the antinociceptive effects of morphine. These data support a model where Gq and Gβγ-dependent signaling cooperatively regulate PLC activation to decrease MOR-dependent antinociceptive potency. Ultimately this could lead to identification of new non-MOR targets that would allow for lower dose utilization of opioid analgesics. " Read more at the source #DrGPCR #GPCR #IndustryNews Subscribe to the Newsletter HERE

September 2022 "The transparency of the cornea along with its dense sensory innervation and resident leukocyte populations make it an ideal tissue to study interactions between the nervous and immune systems. The cornea is the most densely innervated tissue of the body and possesses both immune and vascular privilege, in part due to its unique repertoire of resident immune cells. Corneal nerves produce various neuropeptides that have a wide range of functions on immune cells. As research in this area expands, further insights are made into the role of neuropeptides and their immunomodulatory functions in the healthy and diseased cornea. Much remains to be known regarding the details of neuropeptide signaling and how it contributes to pathophysiology, which is likely due to complex interactions among neuropeptides, receptor isoform-specific signaling events, and the inflammatory microenvironment in disease. However, progress in this area has led to an increase in studies that have begun modulating neuropeptide activity for the treatment of corneal diseases with promising results, necessitating the need for a comprehensive review of the literature. This review focuses on the role of neuropeptides in maintaining the homeostasis of the ocular surface, alterations in disease settings, and the possible therapeutic potential of targeting these systems." Read more at the source #DrGPCR #GPCR #IndustryNews

A role for BET proteins in regulating basal, dopamine-induced and cAMP/PKA-dependent transcription in rat striatal neurons The activity of striatal medium-spiny projection neurons is regulated by D1 and D2 dopamine receptors. The D1 receptor (D1R) is a Gαs/olf-coupled GPCR which activates a cAMP/PKA/DARPP-32 signalling cascade that increases excitability and facilitates plasticity, partly through the regulation of transcription. Upon activation via D1R, PKA can translocate to the nucleus to regulate transcription through the phosphorylation of various targets. One candidate effector of PKA-dependent transcriptional regulation is the BET protein Brd4. It is known that when Brd4 is activated by phosphorylation, it binds more readily to acetylated histones at promoters and enhancers; moreover, in non-neuronal cells, PKA signalling has been shown to increase recruitment of Brd4 to chromatin. However, it is unknown whether BET proteins, or Brd4 specifically, are involved in transcriptional activation by cAMP/PKA in neurons. Here, we demonstrate that in adult rats, inhibition of BET proteins with the bromodomain inhibitor JQ1 suppressed the expression of ~25% of D1R-upregulated genes, while also increasing the expression of a subset of immediate-early genes. We further found that cAMP/PKA signalling promotes Brd4 recruitment to dopamine-induced genes in striatal neurons, and that knockdown of Brd4 attenuates D1R-induced gene expression. Finally, we report that JQ1 treatment downregulated expression of many GPCRs and also impaired ERK1/2 signalling in striatal neurons. Our findings identify the BET protein family, and Brd4 in particular, as novel regulators of basal and D1R-dependent transcription in rat striatal neurons, and delineate complex bi-directional effects of bromodomain inhibitors on neuronal transcription. Read full article

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βarrestin-independent GPCR endocytosis A non-canonical mechanism of GPCR activation cGMP-dependent pathway and a GPCR kinase and confers chemoresistance by mediating glucose metabolic symbiosis GPCR Binders, Drugs, and more Kinetic the TGF-α-induced migration of hepatocellular carcinoma cells via inhibition of the c-Jun N-terminal kinase

Understanding real-time kinetics to predict activity and in vivo target coverage. November 14th: The Application of GPCR Ligand Kinetics to Candidate Design. substitutions and recurrent gene loss in sauropsids Noval insights and therapeutic strategies for tumor-induced kidney

patterns of GPCRs in different immune cell types, including B cells, CD4+ T cells, CD8+ T cells, natural killer

Garcia-Marcos for their excellent work on Protocol to investigate G protein-coupled receptor signaling kinetics Adjust ligand kinetics and tissue disposition for optimal therapeutic activity. agonists A role for plasma membrane Ca2+ ATPases in regulation of cellular Ca2+ homeostasis by sphingosine kinase across phylum Nematoda Target-based discovery of antagonists of the tick (Rhipicephalus microplus) kinin secondary metabolite production in yeast Protocol to investigate G protein-coupled receptor signaling kinetics

Understanding real-time kinetics to predict activity and in vivo target coverage. November 14th : The Application of GPCR Ligand Kinetics to Candidate Design.

🚀🎉 Kilian Roßmann , Joshua Levitz , Johannes Broichhagen for their excellent work on Deuteration Understanding real-time kinetics to predict activity and in vivo target coverage. November 14th : The Application of GPCR Ligand Kinetics to Candidate Design.

Additional kinetic validations must also be verified to comprehend the functions of the proteins.

Additionally, GLP-1R couple to G protein-coupled receptor kinases (GRKs) and recruit β-arrestins, adding 1, another endogenous ligand, oxyntomodulin, exhibits a bias towards extracellular signal-regulated kinase McNeill, S.M., et al., The role of G protein-coupled receptor kinases in GLP-1R β-arrestin recruitment

Topics: New cellular assays, real-time kinetics, and unique GPCR behaviors.

Topics: New cellular assays, real-time kinetics, and unique GPCR behaviors. 🔥 Why You Should Enroll downregulation GPCRs in Cardiology, Endocrinology, and Taste Role of G protein coupled receptors in acute kidney

Delve into new cellular assays, real-time kinetics, and unique GPCR behaviors. 🔥 Why You Should Enroll

Topics cover new cellular assays, real-time kinetics, and unique GPCR behaviors.

, November 7 - 14 -21, and December 5, 2024 (five sessions) Topics:  New cellular assays, real-time kinetics highlight includes congrats to: Madison Walker , Benjamin Myers , et al., for their research on GRK2 kinases tethered agonist signaling in adhesion G protein-coupled receptors GPCR Activation and Signaling A-Kinase-Anchoring-Protein Subtypes Differentially Regulate GPCR Signaling and Function in Human Airway Smooth Muscle GRK2 kinases GFP-inspired dyes Structural basis for the ligand recognition and G protein subtype selectivity of kisspeptin

Before the new semester kicks off, dive into our premium on-demand courses! assays to analyze GPCR ligand behavior Predicting activity and in vivo target coverage with real-time kinetics Ciliary length variations impact cilia-mediated signaling and biological responses The receptor tyrosine kinase

assays to analyze GPCR ligand behavior Predicting activity and in vivo target coverage with real-time kinetics

for effective GPCR discovery Discover: Advanced cellular assays for GPCR ligand behavior Real-time kinetics

Understanding real-time kinetics to predict activity and in vivo target coverage.

Signaling GPCR-MAPK signaling pathways underpin fitness trade-offs in whitefly G protein-coupled receptor kinases

into GPCR Function Structural basis for hormone recognition and distinctive Gq protein coupling by the kisspeptin

Binders, Drugs, and more Target-based discovery of antagonists of the tick (Rhipicephalus microplus) kinin

Growth factor-dependent phosphorylation of Gαi shapes canonical signaling by G protein-coupled receptors Kinetic

signaling network is the crosstalk between G protein-coupled receptors (GPCRs) and receptor tyrosine kinases

GPCR contributor article Extracellular signal-regulated kinases – a potential pathway for GPCR-targeted Adhesion G Protein-Coupled Receptor Gpr126 (Adgrg6) Expression Profiling in Diseased Mouse, Rat, and Human Kidneys