Previously, we identified potent positive crosstalk between insulin/IGF-1 receptors and G protein-coupled shown by FAK phosphorylation at Tyr576/577 and Tyr861, sensitive biomarkers of SFK activity within intact

September 2022 Endothelin-1 Stimulates PAI-1 Protein Expression via Dual Transactivation Pathway Dependent evaluate the role of dual transactivation of EGF and TGF-β receptors in phosphorylation of Smad2L and protein In addition, as an intermediary of G protein-coupled receptor (GPCR) signaling, the functions of ROCK Proteins were investigated<br />by western blotting using protein-specific antibodies against phospho-Smad2 This study is the first attempt to scrutinize the significant role of ROCK in the protein expression

inhibit Ca2+ entry, or directly at SNARE complexes to inhibit Ca2+-dependent synaptotagmin-SNARE complex interactions SIGNIFICANCE STATEMENT Two G protein coupled receptors colocalize at presynaptic sites, to mediate presynaptic

September 2022 Microbial Metabolites Orchestrate a Distinct Multi-Tiered Regulatory Network in the Intestinal Epithelium That Directs P-Glycoprotein Expression "P-glycoprotein (P-gp) is a key component of the intestinal epithelium playing a pivotal role in removal of toxins and efflux of endocannabinoids to prevent excessive inflammation and sustain homeostasis. Recent studies revealed butyrate and secondary bile acids, produced by the intestinal microbiome, potentiate the induction of functional P-gp expression. We now aim to determine the molecular mechanism by which this functional microbiome output regulates P-gp. RNA sequencing of intestinal epithelial cells responding to butyrate and secondary bile acids in combination discovered a unique transcriptional program involving multiple pathways that converge on P-gp induction. Using shRNA knockdown and CRISPR/Cas9 knockout cell lines, as well as mouse models, we confirmed the RNA sequencing findings and discovered a role for intestinal HNF4α in P-gp regulation. These findings shed light on a sophisticated signaling network directed by intestinal microbial metabolites that orchestrate P-gp expression and highlight unappreciated connections between multiple pathways linked to colonic health." Read more at the source #DrGPCR #GPCR #IndustryNews

Bitter taste receptors (TAS2Rs) are a poorly understood subgroup of G protein-coupled receptors (GPCRs

October 2022 "G protein-coupled receptors (GPCRs) are important drug targets characterized by a canonical

The mouse cytomegalovirus G protein-coupled receptor homolog, M33, coordinates key features of in vivo signalling repertoire Common to all cytomegalovirus (CMV) genomes analysed to date is the presence of G protein-coupled Constitutive G protein-coupled M33 signalling is required for these phenotypes, although the contribution constitutively activate phospholipase C β (PLCβ) and downstream cyclic AMP response-element binding protein IMPORTANCE G protein-coupled receptors (GPCRs) act as cell surface molecular "switches" which regulate

G protein-coupled receptor kinase 2 is essential to enable vasoconstrictor-mediated arterial smooth muscle production and circulation of vasoconstrictors, resulting in enhanced signalling through their cognate G protein-coupled GPCR signalling through phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) promotes VSMC proliferation In VSMC, G protein-coupled receptor kinase 2 (GRK2) is known to regulate numerous vasoconstrictor GPCRs

Obesity-induced changes in human islet G protein-coupled receptor expression: Implications for metabolic regulation G protein-coupled receptors (GPCRs) are a large family of cell surface receptors that are

August 2022 G protein-coupled receptor kinase type 2 and β-arrestin2: Key players in immune cell functions and inflammation "G protein-coupled receptor kinase type 2 (GRK2) and β-arrestin2 are representative proteins that regulate the transduction and trafficking of G protein-coupled receptor (GPCR) signaling The kinase GRK2 and the multifunctional scaffolding protein β-arrestin2 are key integrated signaling

Role of G Protein-Coupled Receptors in Hepatic Stellate Cells and Approaches to Anti-Fibrotic Treatment G protein-coupled receptors (GPCRs) are cell surface receptors that mediate the function of a great variety

Odorant G protein-coupled receptors as potential therapeutic targets for adult diffuse gliomas: a systematic analysis and review Odorant receptors (ORs) account for about 60% of all human G protein-coupled receptors

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 Interacting binding insights and conformational consequences of the differential activity of cannabidiol with two endocannabinoid-activated G-protein-coupled receptors "Cannabidiol (CBD), the Here, using computational methods, we investigate the interacting determinants of CBD in two closely related endocannabinoid-activated GPCRs, the G-protein-coupled receptor 55 (GPR55) and the cannabinoid From our detailed characterization, we found particular interacting loci in the binding sites of the

September 2022 "Adhesion G protein-coupled receptors (aGPCRs) are cell-surface proteins with large extracellular In cellular-adhesion assays, LK30 specifically broke the trans-cellular interaction of ADGRL3 with teneurin

October 2022 "We describe production of the human A2A adenosine receptor (A2AAR), a class A G protein-coupled

Constitutive, Basal, and β-Alanine-Mediated Activation of the Human Mas-Related G Protein-Coupled Receptor D Induces Release of the Inflammatory Cytokine IL-6 and Is Dependent on NF-κB Signaling G protein-coupled Members of the Mas-related G protein coupled receptors (MRGPRs), a subfamily of GPCRs, are largely expressed However, involvement of the human Mas-related G-protein coupled receptor D (MRGPRD) in the regulation

counting techniques enable a precise determination of the intracellular abundance and stoichiometry of proteins Consider G-protein-coupled receptors-an expansive class of transmembrane signaling proteins that participate the potential for these techniques to advance our understanding of the role of oligomerization in G-protein-coupled

August 2022 "Three classes of G-protein-coupled receptor (GPCR) partners - G proteins, GPCR kinases, Our analysis suggests that the structures of GPCRs bound to these interaction partners available today particular type of partner; (ii) subtle differences in the orientation of individual residues and/or their interactions

GPR183 by 7 α,25-Dihydroxycholesterol Induces Behavioral Hypersensitivity through Mitogen-Activated Protein Kinase and Nuclear Factor- κ B "Emerging evidence implicates the G-protein coupled receptor (GPCR) GPR183 harvested at the time of peak hypersensitivity implicate potential contributions of mitogen-activated protein

November 2022 "Adhesion G-protein-coupled receptors (aGPCRs) play key roles in a diversity of physiologies A comparison of Gq, Gs, Gi, and G12 engagements with ADGRL3 reveals the key determinant of G-protein Taken together, our study lays the groundwork for understanding aGPCR activation and G-protein-coupling

October 2022 "Recently determined structures of class C G protein-coupled receptors (GPCRs) revealed

October 2022 "Over three decades of research have provided thorough insights into G protein-coupled receptor Eliminating β2AR S-nitrosylation by mutation of C265 augments β2AR protein kinase A signaling, enables β2AR nitric oxide (NO) signaling, renders mice resistant to bronchoconstriction, and protects mice from

October 2022 "Melanocortin 3 receptor (MC3R) is a G-protein coupled receptor (GPCR) that is defined on weight and appetite control, 2) the control of growth, puberty, and circadian rhythm, and, 3) its protein-protein interactions and cellular mechanisms."

Here, we sought to investigate the role of Regulator of G Protein Signaling 7 (RGS7) in hyperlipidemia-dependent

polystyrene nanoparticles in the range of μg/L in C. elegans The aim of this study was to identify Gα proteins mediating function of neuronal G protein-coupled receptors (GPCRs) in controlling the response to polystyrene an animal model, and both gene expression and functional analysis were performed to identify the Gα proteins Therefore, neuronal Gα proteins of GOA-1, GSA-1, and GPA-10 functioned to transduce signals of multiple

phosphorylation, β-arrestin binding and endocytosis, and a very high basal rate of degradation that is not protected

This emphasizes the importance of the Gi/o (pertussis toxin-sensitive G proteins, whose βγ subunits activate Our observations with these prominent commonalities may provide new insights into the phenotype and characteristics