We previously demonstrated that the G protein-coupled receptor (GPCR) arginine vasopressin receptor type1A In CRPC xenografts, antagonizing AVPR2, AVPR1A, or both significantly reduced CRPC tumor growth as well Furthermore, we found that castration-resistant cells produced AVP, the endogenous ligand for arginine

In particular, CBD is able to modulate different receptors in the endocannabinoid system, some of which Here, using computational methods, we investigate the interacting determinants of CBD in two closely While in the former, CBD has been demonstrated to function as an antagonist, the way by which CBD modulates To contextualize the results we looked into the CB1 receptor in complex with a well-established antagonist Our work will pave the way for understanding the CBD pharmacology at a molecular level and aid in harnessing

N-termini that allosterically modify receptor-transducer coupling and mediate intracellular pathway bias "Within Through gene expression analysis in immune and gastrointestinal cells, we show that these isoforms emerge Additionally, we employed optical assays in living cells to thoroughly profile both GPR35 isoforms for We found that a proposed disulfide bridge between the N-terminus and extracellular loop 3, present in both isoforms, is crucial for constitutive G13 activation, while an additional cysteine contributed

Here, we demonstrated that GASP1 was highly expressed in breast cancers, and patients harboring altered GASP1 showed a worse prognosis than those with wild-type GASP1. cell proliferation, colony formation, migration, invasion and xenograft tumor growth in nude mice as well Besides, we found that GASP1 knockout obviously improved the response of breast cancer cells to paclitaxel

Using multiplexed single-cell transcriptomics, we analyze human neural precursor cells (hNPCs) from sporadic Accordingly, in these hiPSC-derived hNPCs and neurons, we observe a shortening of PC. Additionally, we detect a shortening of PC in PINK1 -deficient human cellular and mouse models of familial

We considered whether cholesterol, a prominent component of the plasma membrane, limits the ability of headgroups traverse a dynamically revealed hydrophilic groove between transmembrane helices (TM) 6 and 7 while Here, we present comparative MSM analyses of 150-μs simulations of opsin in cholesterol-free and cholesterol-rich phospholipid scrambling by occupying the TM6/7 interface and stabilizing the closed groove conformation while

as angiogenesis, cell signaling, stemness, metastasis, and drug resistance and inflammation, all of which Few therapeutic agents have shown benefits when administered alone, but a few more have demonstrated clear improvement when administered in combination with other therapeutic molecules. time in the clinic), the therapeutic benefits of the β-adrenergic receptor antagonist, propranolol, were This review highlights the clinical trials in which propranolol is taking part as adjuvant therapy at

The chemoresistance of GSCs is mediated in part by adenosine signaling and ABC transporters, which extrude Transcript and protein levels were determined by RT-qPCR and Western blot, respectively. Cell cycle and apoptosis were determined by flow cytometry. Here, we show for the first time that MRP3 expression is induced under hypoxia through the A2B adenosine

coupled MAS1 receptors (MASR) to inhibit inflammatory mediators and decrease reactive oxygen species within Few studies have identified whether Ang-(1-7) decreases cognitive impairment following closed TBI.

In this study, we found that [Ca2+]i elevation and voltage-dependent current generated by MRGPRB2 activation were correlated with extracellular calcium concentration. The increases in [Ca2+]i and voltage-dependent current caused by MRGPRB2 activation were blocked by U73122

this study, the expression and signaling of β2-ADR in B cells during collagen-induced arthritis (CIA) were investigated to provide an explanation of why only B cells from arthritic mice are able to improve CIA Splenic B cells were isolated via magnetic-activated cell sorting (MACS). analyzed at different time points in naïve and arthritic B cells with and without stimulation of β2- pERK1/2 and pCREB were enhanced only in the late phase of arthritis.

Here, we focused on disclosing the integrin-dependent roles of focal adhesion kinase (protein tyrosine We designed and synthetized peptides that interfered with integrin αIIb binding (pCIB and pCIBm) or mimicked results show that the combination of pGRP with PTK2 inhibition or of pGRP with pCIB > pCIBm in additive ways The suppressive rather than activating effects of pGRP were confined to blood flow at a high shear rate This work thereby supports the role of PTK2 in integrin αIIbβ3 activation and signaling."

Identification and functional characterization of the sulfakinin and sulfakinin receptor in the Chinese white However, there is no report on the functional role of SK in the Chinese white pine beetle, Dendroctonus We have cloned and characterized SK and SKR genes in the D. armandi and carried out bioinformatics The expression levels of the two genes were different between male and female adults, and there were In parallel, injection of SK caused a significant reduction in body weight and increase in mortality

Here, we demonstrate using various fluorescence imaging approaches at the single cell level to measure Furthermore, we show that the molecular basis for biased signaling differences between PTHrP1-36 and

September 2022 "G-protein-coupled receptors (GPCRs) are involved in a wide array of physiological and Here, we find that protease-activated receptor 4 (PAR4) unexpectedly acts as a potent oncogene, inducing A truncated form of β-catenin, ∆N133β-catenin, devoid of lysine, as well as serine/threonine residues β-catenin and a markedly reduced transcriptional activity following PAR4 activation, in contrast to wt Taken together, we reveal that PAR-induced post-transcriptional regulation of β-catenin is centrally

Here, we demonstrate a physical interaction between 5-HT2A and TrkB in vitro and in vivo using co-immunoprecipitation preferential antagonist ketanserin prevented the receptor-mediated downregulation of TrkB phosphorylation without intraperitoneal ketanserin injection increased basal TrkB phosphorylation in the frontal cortex and hippocampus, which

We sought to investigate the therapeutic potential of autophagy‐enhancing agent, trehalose, or related Methods We investigated the therapeutic effects of trehalose and saccharin on macrophage IL‐1β production The mechanisms underlying their anti‐inflammatory effects were assessed using specific inhibitor, genetic

Previously, we identified potent positive crosstalk between insulin/IGF-1 receptors and G protein-coupled Here, we show that a combination of insulin and the GPCR agonist neurotensin induced rapid activation of Src family of tyrosine kinases (SFKs) within PANC-1 cells, as shown by FAK phosphorylation at Tyr576 /577 and Tyr861, sensitive biomarkers of SFK activity within intact cells and Src419 autophosphorylation

transduce signals across the plasma membrane and orchestrate a multitude of physiological processes within We have previously shown, using a combination of experimental and simulation approaches, that membrane In addition, we showed that membrane cholesterol stabilizes the serotonin1A receptor against thermal In the present work, we explored the molecular basis of cholesterol-induced thermal stability of the For this, we explored the possible role of the K101 residue in a cholesterol recognition/interaction

Here, we discuss mechanisms responsible for signalling amplification and compartmentalization in T cell We also take into account the detrimental effect of mutations carried by distinct signalling proteins

Here, we provide evidence that distal carboxyl-terminal tail (C-tail), but not proximal, phosphorylation We demonstrate by pharmacologic inhibition of GRK2/3-mediated phosphorylation of the chemokine receptor In addition, we show that GPCRs that have similarly positioned C-tail phosphoresidues are also able to However, although necessary for some GPCRs, we found that distal C-tail sites might not be sufficient

Corneal nerves produce various neuropeptides that have a wide range of functions on immune cells. be known regarding the details of neuropeptide signaling and how it contributes to pathophysiology, which

Activation of the complement pathway results in the production of bioactive C3a, a product of C3 cleavage, which In light of these new results, it is imperative that we revisit previous studies regarding the role of

Herein, we identified GPR108, a GPCR protein described in innate immune system, is a potential therapeutic We identified gambogic acid (GA), a natural prenylated xanthone, selectively targeting GPR108.

A central question of GPCR drug discovery is to understand what determines the agonism or antagonism We hypothesized that there is a common set of receptor interactions made by ligands of diverse structures We computationally docked ~2700 known β2AR ligands to multiple β2AR structures, generating ca 75 000 We used machine learning (ML) techniques to identify specific interactions that correlate with the agonist We demonstrate with the application of ML methods that it is possible to identify the key interactions

One suggested theory is that cannabinoids regulate a variety of physiological processes within the cells Earlier publications have indicated that expression of CB1 receptor mRNA and protein has been recognized within of skeletal muscle from both murines and humans, thus representing a potentially significant pathway which Murine L6 skeletal muscle cells were used in order to clarify additional possible molecular signaling pathways which contribute to alterations in the CB1 receptor.

Here, we provide evidence that activated human T cells express GLP-1R. 1R was functional, as stimulation with a GLP-1R agonist triggered an increase in intracellular cAMP, which Through multimodal single-cell CITE- and TCR-sequencing, we detected GLP-1R expression in 29–34% of the Finally, we demonstrated the presence of GLP-1R+CD4+ T cells in skin from patients with allergic contact Given the high induction of GLP-1R in human iTreg cells, we hypothesize that GLP-1R+ iTreg cells play

In this review, we discuss what is currently known regarding the contribution of mGluR2 and mGluR3 to sclerosis, Alzheimer's disease, Huntington's disease, Parkinson's diseases, schizophrenia and depression as well We then highlight the evidence supporting the use of various drugs including orthosteric and allosteric