TY - JOUR. T1 - G protein-coupled receptor Gpr4 senses amino acids and activates the cAMP-PKA pathway in Cryptococcus neoformans. AU - Xue, Chaoyang. AU - Bahn, Yong Sun. AU - Cox, Gary M.. AU - Heitman, Joseph. PY - 2006/2/1. Y1 - 2006/2/1. N2 - The Gα protein Gpa1 governs the cAMP-PKA signaling pathway and plays a central role in virulence and differentiation in the human fungal pathogen Cryptococcus neoformans, but the signals and receptors that trigger this pathway were unknown. We identified seven putative proteins that share identity with known G protein-coupled receptors (GPCRs). One protein, Gpr4, shares limited sequence identity with the Dictyostelium discoideum cAMP receptor cAR1 and the Aspergillus nidulans GPCR protein GprH and also shares structural similarity with the Saccharomyces cerevisiae receptor Gpr1. gpr4 mutants exhibited reduced capsule production and mating defects, similar to gpa1 mutants, and exogenous cAMP suppressed both gpr4 mutant phenotypes. Epistasis analysis ...

The Gpr1 G protein-coupled receptor regulates filamentous growth: Our studies reveal that the G protein-coupled receptor Gpr1 regulates pseudohyphal differentiation in S. cerevisiae (Figure 9). The Gpr1 receptor also regulates invasive growth of haploid strains and is required for expression of the FLO11 gene encoding a cell surface flocculin. The phenotypes of mutant strains lacking the Gpr1 receptor are similar to those of mutant strains lacking the Gα protein Gpa2, and genetic evidence supports a model in which ligand binding to the Gpr1 receptor activates Gpa2p via a direct interaction. The downstream elements of this signaling pathway consist of adenylyl cyclase, which is activated by Gpa2p to produce cAMP (Nakafukuet al. 1988; Colomboet al. 1998), resulting in activation of PKA (Figure 9). Recent studies have revealed that the Tpk2 catalytic subunit of PKA regulates pseudohyphal differentiation via the Sfl1 and Flo8 transcription factors that regulate expression of the cell surface ...

TY - JOUR. T1 - Sexually dimorphic role of G protein-coupled estrogen receptor (GPER) in modulating energy homeostasis. AU - Davis, Kathryn E.. AU - Carstens, Elizabeth J.. AU - Irani, Boman G.. AU - Gent, Lana M.. AU - Hahner, Lisa M.. AU - Clegg, Deborah J.. N1 - Funding Information: We thank Dr. Roger Unger for providing us the human leptin. We also thank Dr. Nedungadi for performing the leptin and insulin assays. This work was supported by the National Institute of Health grant numbers DK073689 and DK088761 .. PY - 2014/6. Y1 - 2014/6. N2 - This article is part of a Special Issue Energy Balance.The classical estrogen receptors, estrogen receptor-α and estrogen receptor-β are well established in the regulation of body weight and energy homeostasis in both male and female mice, whereas, the role for G protein-coupled estrogen receptor 1 (GPER) as a modulator of energy homeostasis remains controversial. This study sought to determine whether gene deletion of GPER (GPER KO) alters body ...

TY - JOUR. T1 - G protein-coupled estrogen receptor is apoptotic and correlates with increased distant disease-free survival of estrogen receptor-positive breast cancer patients. AU - Broselid, Stefan. AU - Cheng, Benxu. AU - Sjöström, Martin. AU - Lövgren, Kristina. AU - Klug-De Santiago, Heather L.P.. AU - Belting, Mattias. AU - Jirström, Karin. AU - Malmström, Per. AU - Olde, Björn. AU - Bendahl, Pär Ola. AU - Hartman, Linda. AU - Fernö, Mårten. AU - Leeb-Lundberg, L. M.Fredrik. N1 - Copyright: Copyright 2013 Elsevier B.V., All rights reserved.. PY - 2013/4/1. Y1 - 2013/4/1. N2 - Purpose: G protein-coupled estrogen receptor 1 (GPER1), previously named GPR30, is a membrane receptor reported to mediate nongenomic estrogen responses. We investigated if GPER1 expression correlates with any clinicopathologic variables and distant disease-free survival (DDFS) in patients with breast cancer, if any prognostic impact of the receptor is dependent on estrogen receptor-α (ER-α) status, and if ...

Adhesion G protein-coupled receptors (adhesion GPCRs) are a class of 33 human protein receptors with a broad distribution in embryonic and larval cells, cells of the reproductive tract, neurons, leukocytes, and a variety of tumours. Adhesion GPCRs are found throughout metazoans and are also found in single-celled colony forming choanoflagellates such as Monosiga brevicollis and unicellular organisms such as Filasterea. The defining feature of adhesion GPCRs that distinguishes them from other GPCRs is their hybrid molecular structure. The extracellular region of adhesion GPCRs can be exceptionally long and contain a variety of structural domains that are known for the ability to facilitate cell and matrix interactions. Their extracellular region contains the membrane proximal GAIN (GPCR-Autoproteolsis INducing) domain. Crystallographic and experimental data has shown this structurally conserved domain to mediate autocatalytic processing at a GPCR-proteolytic site (GPS) proximal to the first ...

Monya Baker. Ascl2, a transcription factor and Wnt target, switches on a stem cell program in the gut. In the search for what makes a stem cell a stem cell, Hans Clevers and colleagues at Hubrecht Institute-KNAW, the Netherlands, have found a transcription factor expressed uniquely in the gut1. Deletion of the gene, called Achaete scute-like 2 (Ascl2), completely ablates stem cell activity. Activating the gene in non-stem cells causes the cells to take on stem cell characteristics, including making stem cell markers and reproducing the structures and specialized cell types that normal intestinal stem cells produce. Previously, Clevers had done complex cell- and lineage-tracking experiments both to establish Lgr5 (leucine-rich repeat-containing G protein-coupled receptor 5) as a marker of stem cells in the small intestine and to pinpoint the location of intestinal stem cells at the base of crypts, or the spaces between villi.. In the current work, the ...

The classical estrogen receptors, estrogen receptor -α- and estrogen receptor β, are well established in the regulation of body weight and energy homeostasis in both male and female mice, whereas, the role for a G protein-coupled estrogen receptor 1 (GPER) as a modulator of energy homeostasis remains controversial. This study sought to determine whether gene deletion of GPER (GPER KO) alters body weight, body adiposity, food intake, and energy homeostasis in both males and females. Male mice lacking GPER developed moderate obesity and larger adipocyte size beginning at 8 weeks of age, with significant reductions in energy expenditure, but not food intake or adipocyte number. Female GPER KO mice developed increased body weight relative to WT females a full 6 weeks later than the male GPER KO mice. Female GPER KO mice also had reductions in energy expenditure, but not significant increases in body fat content. Consistent with their decrease in energy expenditure, GPER KO males and females showed ...

G protein-coupled Estrogen Receptor 1 is a member of the GPCR family and is encoded in Humans by the GPER gene. Alternate transcriptional splice variants that encode the same protein have been characterized. It is a member of the rhodopsin-like family and is localized to the endoplasmic reticulum membrane. GPER binds estrogen with high affinity, resulting in intracellular calcium mobilization and synthesis of phosphatidylinositol 3,4,5-trisphosphate in the nucleus.

Endogenous estrogens mediate protective effects in the cardiovascular system in part due to rapid activation of endothelial nitric oxide synthase (eNOS), which involves the classical estrogen receptor (ER) α. Estrogen-dependent increases in NO bioactivity may also be mediated by the G protein-coupled estrogen receptor (GPER/GPR30), although the contribution of GPER to the overall response to estrogen and the mechanisms involved remain unclear. We have investigated GPER-mediated NO signaling in telomerase-immortalized human umbilical vein endothelial (TIVE) cells as well as estrogen-dependent, GPER-mediated relaxation in mouse aortae. Similar to the non-selective ER agonist 17β-estradiol (E2), the GPER-selective agonist G-1 stimulated phosphorylation of eNOS (ser1171) at 100 nM vs. 0.01% DMSO vehicle (53 +/-7 vs. 19+/-4, p=0.035, n=4). Colorimetric detection of nitric oxide demonstrated that Acetylcholine (Ach) (536 +/-18), E2 (425+/- 18) and G-1 (308 +/-18) also increased NO production in ...

The role of basal suppression of Sonic hedgehog (Shh) pathway and its interaction with Indian hedgehog (Ihh) signaling during limb/skeletal morphogenesis is not well understood. The orphan G-protein-coupled receptor, Gpr161 localizes to primary cilia, and functions as a negative regulator of Shh signaling by promoting Gli transcriptional repressor versus activator formation. Here, we show that forelimb buds are not formed in Gpr161 knockout mice embryos despite establishment of prospective limb fields. Limb-specific deletion of Gpr161 resulted in prematurely expanded Shh signaling and ectopic Shh-dependent patterning defects to cause polysyndactyly. In addition, endochondral bone formation in forearms, including formation of both trabecular bone and bone collar was prevented. Endochondral bone formation defects resulted from accumulation of proliferating round/periarticular-like chondrocytes, lack of differentiation into columnar chondrocytes, and corresponding absence of Ihh signaling. Gpr161 ...

Lysophosphatidylinositol (LPI) is a bioactive lipid generated by phospholipase A2 which is believed to play an important role in several diseases. Indeed LPI can affect various functions such as cell growth, differentiation and motility, in a number of cell-types, including cancer cells, endothelial cells and nervous cells. Despite the fact that LPI-induced cellular functions had been known for more than twenty years, the recent discovery that in several cell-types the orphan G protein-coupled receptor GPR55 acts as the specific receptor for LPI has fuelled novel interest in this lysolipid. Different research groups, including our own, have recently suggested that LPI may be the specific and functional ligand for GPR55, triggering signalling cascades that are relevant to cell proliferation, migration, survival and tumourigenesis. Recently published data suggest that the LPI/GPR55 axis plays an important role in different physiological and pathological contexts. Here we review the available data

A lysophospholipid series, such as lysophosphatidic acid, lysophosphatidylserine, and lysophosphatidylcholine (LPC), is a bioactive lipid mediator with diverse physiological and pathological functions. LPC has been reported to induce insulin secretion from pancreatic beta-cells, however, the precise …

Neuropeptide B (NPB) and the structurally related neuropeptide W (NPW) have recently been identified as the endogenous ligands of the orphan G protein-coupled receptors GPR7 and GPR8. Whereas NPW is a high-affinity ligand for both GPR7 and GPR8, NPB activates only GPR7 in sub-nanomolar concentrations. GPR7 is highly conserved in both human and rodent orthologs while GPR8 has not been found in rodents. GPR7 mRNA is expressed in discrete regions of the hypothalamus suggesting a role in the regulation of energy homeostasis and neuroendocrine axes. In the present study, we have generated and extensively characterized antibodies that exert selective specificity for NPB. In dot-blot assays, these antibodies detected NPB but not NPW. Immunofluorescent staining of rat brain sections revealed moderately dense plexus of NPB-immunoreactive fibers and terminals in discrete areas of the hypothalamus. Neuronal somata were only seen in colchicine-treated rats. This immunostaining was completely abolished by

387554453 - EP 1118621 A4 2003-06-25 - NOVEL G PROTEIN-COUPLED RECEPTOR PROTEIN AND DNA THEREOF - [origin: WO0020456A1] A human-origin G protein-coupled receptor protein or its peptide fragment or its salt, a nucleic acid encoding this receptor protein and its derivative, etc. The human hippocampus-origin G protein-coupled receptor protein or the nucleic acid encoding the same and its derivative are usable in determining a ligand (an agonist) to the G protein-coupled receptor protein, as preventives and/or remedies for diseases in association with dysfunction of the G protein-coupled receptor protein, as gene diagnostics, in a method for screening a compound capable of varying the expression dose of the G protein-coupled receptor protein or its peptide fragment, etc.[origin: WO0020456A1] A human-origin G protein-coupled receptor protein or its peptide fragment or its salt, a nucleic acid encoding this receptor protein and its derivative, etc. The human hippocampus-origin G protein-coupled receptor

The G protein-coupled receptor GPR30 has recently been identified as a nonnuclear estrogen receptor. Reverse transcriptase-polymerase chain reaction revealed expression of GPR30 mRNA in varying quantities in the rat spinal cord, dorsal root ganglia, nodose ganglia, trigeminal ganglia, hippocampus, brain stem, and hypothalamus. Immunohistochemical studies that used a rabbit polyclonal antiserum against the human GPR30 C-terminus revealed a fine network of GPR30-immunoreactive (irGPR30) cell processes in the superficial layers of the spinal cord; some of which extended into deeper laminae. A population of neurons in the dorsal horn and ventral horn were irGPR30. Dorsal root, nodose, and trigeminal ganglionic neurons displayed varying intensities of irGPR30. Positively labeled neurons were detected in the major pelvic ganglion, but not in the superior cervical ganglion. A population of chromaffin cells in the adrenal medulla was irGPR30, so were cells of the zona glomerulosa. Double-labeling the ...

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Global and Chinese Free Fatty Acid Receptor Industry, 2017 Market Research Report Size and Share Published in 2017-07-21 Available for US$ 3000 at Researchmoz.us

G protein-coupled receptors (GPCRs) are membrane proteins critical in cellular signaling, making them important targets for therapeutics. The activation of GPCRs is central to their function, requiring multiple conformations of the GPCRs in their activation landscape. To enable rational design of GPCR-targeting drugs, it is essential to obtain the ensemble of atomistic structures of GPCRs along their activation pathways. This is most challenging for structure determination experiments, making it valuable to develop reliable computational structure prediction methods. In particular, since the active-state conformations are higher in energy (less stable) than inactive-state conformations, they are difficult to stabilize. In addition, the computational methods are generally biased toward lowest energy structures by design and miss these high energy but functionally important conformations. To address this problem, we have developed a computationally efficient ActiveGEnSeMBLE method that ...

Free fatty acids (FFA) are produced in the intestine by microbial fermentation. Recently, a family of G protein-coupled receptors (GPR) acting as FFA transporters has been reported including GPR120, which is expressed by intestinal epithelial cells. The GPR120 has been reported to affect the expression of glucagon-like peptide (GLP)-1 as well as function as a control point for anti-inflammatory effects. The aim of the present study was to evaluate whether 12 selected intestinal bacteria, representing the 4 major phyla present in the intestine, affect intestinal epithelial cell GPR120 and GLP-1 mRNA abundance. Supernatants of the 12 bacteria were added to differentiated Caco-2 intestinal epithelial cells cultured on filter inserts in concentrations corresponding to a cell:bacteria ratio of 1:200. After 4 h of incubation, changes in cellular mRNA of GLP-1 and GPR120 by bacterial supernatant were examined using real-time reverse transcriptase polymerase chain reaction. The abundance of GLP-1 mRNA ...

G protein-coupled receptors (GPCRs) which are also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors (GPLR), constitute a large protein family of receptors that detect molecules outside the cell and activate internal signal transduction pathways and, ultimately, cellular responses. Coupling with G proteins, they are called seven-transmembrane receptors because they pass through the cell membrane seven times. G protein-coupled receptors are found only in eukaryotes, including yeast, choanoflagellates, and animals. The ligands that bind and activate these receptors include light-sensitive compounds, odors, pheromones, hormones, and neurotransmitters, and vary in size from small molecules to peptides to large proteins. G protein-coupled receptors are involved in many diseases, and are also the target of approximately 34% of all modern medicinal drugs. There are two principal signal transduction pathways ...

Citation. Fraser, C. M.. Structure and Functional Analysis of G Protein-coupled Receptors and Potential Diagnostic Ligands. J Nucl Med. 1995 Jun 01; 36(6): 17S-21S.. PubMed Citation. Abstract. G protein-coupled receptors are a diverse class of proteins that mediate signal transduction across the plasma membrane. More than 200 receptors in this extended gene family have been cloned, and comparison of the deduced amino-acid sequences indicates that these proteins have marked homology and share a common membrane topology consisting of seven transmembrane helices. Although there is considerable variability in the physiologic ligands responsible for receptor activation, all receptors in this group interact with trimeric, guanine nucleotide-binding proteins to initiate signaling cascades in the cell cytosol. To investigate the structural motifs responsible for ligand binding, we have established a model system to express heterologously human G protein-coupled receptors in a mammalian cell line. This ...

Monies et al. (2017) studied the genomic landscape of Saudi Arabia based on the findings of 1000 diagnostic panels and exomes. One patient, an 18-year-old male from a consanguineous family, presented with exercise-induced muscle pain, rhabdomyolysis and a post-exercise CK level ,15000. He had no tenderness, muscle atrophy or hypertrophy and was otherwise asymptomatic. Whole exome sequencing helped identify a homozygous mutation (c.170C,A, p.T57N) in exon 2 of the patients ADGRG7 gene. This gene mutation was considered a candidate for pathogenicity due to several reasons: it was a novel variant located within the autozygome and was predicted to be deleterious; and the ADGRG7 gene is a G protein-coupled receptor seen to be expressed in the skeletal muscle. The authors noted that further studies are required to confirm this association. ...

Apelin is an endogenous peptide capable of binding the apelin receptor (APJ), which was originally described as an orphan G-protein-coupled receptor. Apelin and APJ are widely expressed in various tissues and organ systems. They are implicated in different key physiological processes such as angiogenesis, cardiovascular functions, cell proliferation and energy metabolism regulation. On the other hand, this ligand receptor couple is also involved in several pathologies including diabetes, obesity, cardiovascular disease and cancer ...

Apelin is an endogenous peptide capable of binding the apelin receptor (APJ), which was originally described as an orphan G-protein-coupled receptor. Apelin and APJ are widely expressed in various tissues and organ systems. They are implicated in different key physiological processes such as angiogenesis, cardiovascular functions, cell proliferation and energy metabolism regulation. On the other hand, this ligand receptor couple is also involved in several pathologies including diabetes, obesity, cardiovascular disease and cancer ...

TY - JOUR. T1 - A Novel Antiinflammatory Role for the Short-Chain Fatty Acids in Human Labor. AU - Voltolini, Chiara. AU - Battersby, Sharon. AU - Etherington, Sophie L.. AU - Petraglia, Felice. AU - Norman, Jane E.. AU - Jabbour, Henry N.. N1 - RIS file. PY - 2012. Y1 - 2012. N2 - Human parturition is an inflammatory process that can be activated prematurely by pathological stimuli. This study investigated the expression of G protein-coupled receptors GPR43 and GPR41 receptors in human uteroplacental tissues and the role of short-chain fatty acids (SCFA) in modulating inflammatory pathways in fetal membranes. Expression of GPR43 and GPR41 was investigated in uteroplacental tissues collected from women delivering at term or preterm after ethical approval and patient informed consent. The effect of SCFA on expression of inflammatory genes was assessed in amnion explants after culture with a mimetic of infection (lipopolysaccharide, LPS). Sodium propionate effect on LPS-induced neutrophil ...

Chemoattractant for blood monocytes, memory T-helper cells and eosinophils. Causes the release of histamine from basophils and activates eosinophils. May activate several chemokine receptors including CCR1, CCR3, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant RANTES protein induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). The processed form RANTES(3-68) acts as a natural chemotaxis inhibitor and is a more potent inhibitor of HIV-1-infection. The second processed form RANTES(4-68) exhibits reduced chemotactic and HIV-suppressive activity compared with RANTES(1-68) and RANTES(3-68) and is generated by an unidentified enzyme associated with monocytes and neutrophils (PubMed:16791620, PubMed:1380064, PubMed:8525373, PubMed:9516414, PubMed:15923218). May also be an agonist of the G protein-coupled receptor GPR75, stimulating inositol trisphosphate production and calcium mobilization ...

The omega-3 fatty acids have anti-inflammatory and antidiabetic effects in humans. Now, Oh et al. (2010) demonstrate that the G protein-coupled receptor GPR120 is a receptor for omega-3 fatty acids on macrophages and fat cells. Activation of GPR120 b

This gene encodes a protein that has a domain resembling seven transmembrane G protein-coupled hormone receptors (7TM receptors) at its C-terminus. The N-terminus of the encoded protein has six EGF-like modules, separated from the transmembrane segments by a serine/threonine-rich domain, a feature reminiscent of mucin-like, single-span, integral membrane glycoproteins with adhesive properties. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012 ...

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Apelin is an endogenous peptide capable of binding the apelin receptor (APJ), which was originally described as an orphan G-protein-coupled receptor. Apelin and APJ are widely expressed in various tissues and organ systems. They are implicated in different key physiological processes such as angiogenesis, cardiovascular functions, cell proliferation and energy metabolism regulation. On the other hand, this ligand receptor couple is also involved in several pathologies including diabetes, obesity, cardiovascular disease and cancer ...

Orphan receptor that regulates migration of lymphatic endothelial cells in vitro via the small GTPases RhoA and CDC42 (PubMed:24178298). Regulates B-cell development (By similarity). Seems to signal through G-alpha(q)-proteins (PubMed:22575658).

Chen P, Piao X, Bonaldo P. (2015). Role of macrophages in Wallerian degeneration and axonal regeneration after peripheral nerve injury. Acta Neuropathologica 130, 605-618. Schöneberg T, Liebscher I, Luo R, Monk KR, Piao X. (2015). Tethered agonists: a new mechanism underlying adhesion G protein-coupled receptor activation. Journal of Receptors and Signal Transduction 35, 220-223. Rao TN, Marks-Bluth J, Sullivan J, Gupta MK, Chandrakanthan V, Fitch SR, Ottersbach K, Jang YC, Piao X, Kulkarni RN, Serwold T, Pimanda JE, Wagers AJ. (2015). High-level Gpr56 expression is dispensable for the maintenance and function of hematopoietic stem and progenitor cells in mice. Stem cell research 14, 307-322. Hamann J, Aust G, Araç D, Engel FB, Formstone C, Fredriksson R, Hall RA, Harty BL, Kirchhoff C, Knapp B, Krishnan A, Liebscher I, Lin HH, Martinelli DC, Monk KR, Peeters MC, Piao X, Prömel S, Schöneberg T, Schwartz TW, Singer K, Stacey M, Ushkaryov YA, Vallon M, Wolfrum U, Wright MW, Xu L, Langenhan T, ...

Mol Pharmacol 82(5):777-783. 080309, PubMed PMID: 22821233, PubMed Central PMCID: PMC3477231 36 A. Krishnan et al. 49. Underwood CR, Garibay P, Knudsen LB, Hastrup S, Peters GH, Rudolph R et al (2010) Crystal structure of glucagon-like peptide-1 in complex with the extracellular domain of the glucagon-like peptide-1 receptor. J Biol Chem 285(1):723-730. M109. 033829, PubMed PMID: 19861722, PubMed Central PMCID: PMC2804221 50. Wouters MA, Rigoutsos I, Chu CK, Feng LL, Sparrow DB, Dunwoodie SL (2005) Evolution of distinct EGF domains with specific functions. ADGRCs are among the oldest aGPCRs. ADGRC consists of nine cadherin repeats (110 aa), followed by six EGF-like domains (see Sect. 1), two LAG domains, and an HBD (see Sect. 1). The cadherin repeats play a role in extracellular calcium binding [90]. The 3D structure of several cadherin domains in other proteins has been solved lately. These cadherin domains are formed by seven beta-strands and show similarity to immunoglobulin constant domains ...

GPR84 is an orphan G-protein-coupled receptor that is expressed on immune cells and implicated in several inflammatory diseases. The validation of GPR84 as a therapeutic target is hindered by the narrow range of available chemical tools and consequent poor understanding of GPR84 pathophysiology. Here we describe the discovery and characterization of DL-175, a potent, selective, and structurally novel GPR84 agonist and the first to display significantly biased signaling across GPR84-overexpressing cells, primary murine macrophages, and human U937 cells. By comparing DL-175 with reported GPR84 ligands, we show for the first time that biased GPR84 agonists have markedly different abilities to induce chemotaxis in human myeloid cells, while causing similar levels of phagocytosis enhancement. This work demonstrates that biased agonism at GPR84 enables the selective activation of functional responses in immune cells and delivers a high-quality chemical probe for further investigation.

Equine degenerative myeloencephalopathy (EDM), a neurological disease of young horses, causes progressive development of symmetric ataxia predominantly in the pelvic limbs.

Various receptors transduce signals in immune cells by associating with G proteins, and the signals modulate cellular motility (e.g., S1P and chemokine receptors; refs. 12, 13). PTX from Bordetella pertussis is an ADP-ribosylating toxin that prevents G protein-coupled receptor activation and consequently disrupts the signal transduction cascade for lymphocyte egress (14, 15). In order to clarify whether G protein-coupled receptors are involved in the migration of lymphocytes from aLNs to peripheral lymphoid tissues in SCID mice, aLNs were produced in BALB/c mice that had been immunized with alum-precipitated NP-OVA. The aLNs were then cultured in vitro for 3 hours in medium containing PTX before transplantation into SCID mice. After 2 i.v. immunizations with NP-OVA as described above, aLNs, spleens, and BM cells of recipient mice were collected. The number of IgG1 NP-specific AFCs in aLNs was greatly increased by treatment with PTX before transfer into SCID mice (Figure 8A). Conversely, the ...

McKee KK, Tan CP, Palyha OC, Liu J, Feighner SD, Hreniuk DL, Smith RG, Howard AD, Van der Ploeg LH (Mar 1998). Cloning and characterization of two human G protein-coupled receptor genes (GPR38 and GPR39) related to the growth hormone secretagogue and neurotensin receptors. Genomics 46 (3): 426-34. DOI:10.1006/geno.1997.5069. PMID 9441746. ...

The present study provides evidence that endogenous GPER regulates vascular activity of prostanoid-dependent endothelial vasoconstriction. Chronic deficiency of the GPER gene has no effect on NO bioactivity but is associated with enhanced VSMC contraction to endothelium-dependent, COX-derived vasoconstrictor prostanoids and to direct TP receptor activation. In addition, histological and immunohistochemical analyses revealed structurally normal arteries in GPER0 mice. By contrast, acute blockade of GPER decreases both basal and stimulated endothelial NO bioactivity and increases EDCF-mediated responses while contractions to a TP receptor agonist remain unchanged. These data identify GPER as a novel, inhibitory regulator of endothelial vasoconstrictor prostanoids and as the first estrogen receptor specifically associated with the regulation of endothelial vasoconstriction.. Acetylcholine induces the release of 2 counteracting endothelial mediators in the mouse aorta: NO-mediated relaxation is ...

The novel G protein-coupled receptor APJ, recently paired with the proposed cognate peptide ligand apelin, mediates potent vasodilator and positive inotropic actions in rats. Radioligand binding showed apelin receptors in rat and human heart and human large conduit vessels. The specific cell types e …

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Jung BP, Nguyen T, Kolakowski LF Jr, Lynch KR, Heng HH, George SR, ODowd BF (Feb 1997). Discovery of a novel human G protein-coupled receptor gene (GPR25) located on chromosome 1. Biochem Biophys Res Commun 230 (1): 69-72. PMID 9020062. doi:10.1006/bbrc.1996.5828. Cite uses deprecated parameter ...

Southern, Craig; Cook, Jennifer M.; Neetoo-Isseljee, Zaynab; Taylor, Debra L.; Kettleborough, Catherine A.; Merritt, Andy; Bassoni, Daniel L.; Raab, William J.; Quinn, Elizabeth; Wehrman, Tom S.; Davenport, Anthony P.; Brown, Andrew J.; Green, Andrew; Wigglesworth, Mark J.; Rees, Steve (2013). Screening β-Arrestin Recruitment for the Identification of Natural Ligands for Orphan G-Protein-Coupled Receptors. Journal of biomolecular screening. SAGE Publications. 18 (5): 599-609. doi:10.1177/1087057113475480. ISSN 1087-0571. PMID 23396314 ...

Cell surface N-glycoproteins provide a key interface of cells to their environment and therapeutic entry points for drug and biomarker discovery. Their comprehensive description denotes therefore a formidable challenge. The β-cells of the pancreas play a crucial role in blood glucose homeostasis and disruption of their function contributes to diabetes. By combining cell surface and whole cell capturing technologies with high-throughput quantitative proteomic analysis, we report on the identification of a total of 956 unique N-glycoproteins from mouse MIN6 β-cells and human islets. Three-hundred-forty-nine of these proteins encompass potential surface N-glycoproteins and include orphan G-protein-coupled receptors, novel proteases, receptor protein kinases and phosphatases. Interestingly, stimulation of MIN6 β-cells with glucose and the hormone GLP1, known stimulators of insulin secretion, causes significant changes in surface N-glycoproteome expression. Taken together, this β-cell ...

G protein-coupled receptor that is activated by a major product of dietary fiber digestion, the short chain fatty acids (SCFAs), and that plays a role in the regulation of whole-body energy homeostasis and in intestinal immunity. In omnivorous mammals, the short chain fatty acids acetate, propionate and butyrate are produced primarily by the gut microbiome that metabolizes dietary fibers. SCFAs serve as a source of energy but also act as signaling molecules. That G protein-coupled receptor is probably coupled to the pertussis toxin-sensitive, G(i/o)-alpha family of G proteins but also to the Gq family (PubMed:12496283, PubMed:12711604, PubMed:23589301). Its activation results in the formation of inositol 1,4,5-trisphosphate, the mobilization of intracellular calcium, the phosphorylation of the MAPK3/ERK1 and MAPK1/ERK2 kinases and the inhibition of intracellular cAMP accumulation. May play a role in glucose homeostasis by regulating the secretion of GLP-1, in response to short-chain fatty acids ...

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GPR41 is a G protein-coupled receptor activated by short chain fatty acids. site located in the intergenic region of a bicistronic mRNA. This novel sequence business may be utilized to enable coordinated rules of the fatty acid receptors GPR40 and GPR41. and flanking the GPR40 ORF indicate 5- and 3UTRs. upstream of the GPR40 … Studies from our laboratory have shown that selective manifestation of GPR40 in beta cells is definitely controlled by transcriptional mechanisms (21). Of particular importance is definitely HR2, a beta cell-specific transcriptional enhancer located 1.1 kb upstream of the gene (Fig. 1method, relative to control (22). 5-Quick 14919-77-8 supplier Amplification of cDNA Ends (5-RACE) 5-RACE was performed as explained previously (21) with the following modifications. Method A, 1st strand cDNA was synthesized from 5 g of DNase-treated TC1 RNA, using reverse transcriptase (SuperScript II; Invitrogen) according to 14919-77-8 supplier the manufacturers instructions. The reaction ...

G-protein coupled receptor for medium and long chain saturated and unsaturated fatty acids that plays an important role in glucose homeostasis. Fatty acid binding increases glucose-stimulated insulin secretion, and may also enhance the secretion of glucagon-like peptide 1 (GLP-1). May also play a role in bone homeostasis; receptor signaling activates pathways that inhibit osteoclast differentiation (By similarity). Ligand binding leads to a conformation change that triggers signaling via G-proteins that activate phospholipase C, leading to an increase of the intracellular calcium concentration. Seems to act through a G(q) and G(i)-mediated pathway.

rat G protein-coupled receptor AGR9: a mammalian receptor, member of the G protein-coupled receptor family; expressed in cardiovascular, CNS & digestive systems; amino acid sequence given in first source

Kit contents: 1. MICROTITER PLATE * 1 2. ENZYME CONJUGATE*1 vial 3. STANDARD A*1 vial 4. STANDARD B*1 vial 5. STANDARD C*1 vial 6. STANDARD D*1 vial 7. STANDARD E*1 vial 8. STANDARD F*1 vial 9. SUBSTRATE A*1 vial 10. SUBSTRATE B*1 vial 11. STOP ...

Looking for online definition of free fatty acid receptor 3 in the Medical Dictionary? free fatty acid receptor 3 explanation free. What is free fatty acid receptor 3? Meaning of free fatty acid receptor 3 medical term. What does free fatty acid receptor 3 mean?

Recent evidence suggests that the trace amine-associated receptor 1 (TAAR1) plays a pivotal role in the regulation of dopamine (DA) transmission and psychostimulant action. Several selective TAAR1 agonists have previously shown efficacy in models of cocaine addiction. However, the effects of TAAR1 activation on methamphetamine (METH)-induced behaviours are less well understood, as indeed are the underlying neurochemical mechanisms mediating potential interactions between TAAR1 and METH. Here, in a progressive ratio schedule of reinforcement the partial TAAR1 agonist, RO5263397, reduced the break-point for METH self-administration, while significantly increasing responding maintained by food reward. Following self-administration and extinction training, RO5263397 completely blocked METH-primed reinstatement of METH seeking. Moreover, when used as a substitute, unlike a low dose of METH, which sustained vigorous responding when substituting for the training dose of METH, RO5263397 was not self

Looking for online definition of leucine-rich repeat-containing G-protein coupled receptor 5 in the Medical Dictionary? leucine-rich repeat-containing G-protein coupled receptor 5 explanation free. What is leucine-rich repeat-containing G-protein coupled receptor 5? Meaning of leucine-rich repeat-containing G-protein coupled receptor 5 medical term. What does leucine-rich repeat-containing G-protein coupled receptor 5 mean?

Lack of high potency agonists has restricted analysis of the G protein-coupled receptor GPR35. Moreover, marked variation in potency and/or affinity of current ligands between human and rodent orthologs of GPR35 has limited their productive use in rodent models of physiology. Based on the reported modest potency of the antiasthma and antiallergic ligands cromolyn disodium and nedocromil sodium, we identified the related compounds lodoxamide and bufrolin as high potency agonists of human GPR35. Unlike previously identified high potency agonists that are highly selective for human GPR35, both lodoxamide and bufrolin displayed equivalent potency at rat GPR35. Further synthetic antiallergic ligands, either sharing features of the standard surrogate agonist zaprinast, or with lodoxamide and bufrolin, were also shown to display agonism at either human or rat GPR35. Because both lodoxamide and bufrolin are symmetric di-acids, their potential mode of binding was explored via mutagenesis based on ...

Triple-negative breast cancer (TNBC) accounts for 20% of breast cancer in women and lacks an effective targeted therapy. Therefore, finding common vulnerabilities in these tumors represents an opportunity for more effective treatment. Despite the growing appreciation of G-protein-coupled receptor (GPCR)-mediated signaling in cancer pathogenesis, very little is known about the role GPCRs play in TNBC. Using genomic information of human breast cancer, we have discovered that the orphan GPCR, G-protein-coupled receptor 161 (GPR161) is overexpressed specifically in TNBC and correlates with poor prognosis. Knockdown of GPR161 impairs proliferation of human basal breast cancer cell lines. Overexpression of GPR161 in human mammary epithelial cells increases cell proliferation, migration, intracellular accumulation of E-cadherin, and formation of multiacinar structures in 3D culture. GPR161 forms a signaling complex with the scaffold proteins beta-arrestin 2 and Ile Gln motif containing GTPase ...

Adhesion G Protein-Coupled Receptor L4 (ADGRL4/ELTD1) is an endothelial cell adhesion G protein-coupled receptor (aGPCR) which regulates physiological and tumour angiogenesis, providing an attractive target for anti-cancer therapeutics. To date, ADGRL4/ELTD1s full role and mechanism of function within endothelial biology remains unknown, as do its ligand(s). In this study, ADGRL4/ELTD1 silencing, using two independent small interfering RNAs (siRNAs), was performed in human umbilical vein endothelial cells (HUVECS) followed by transcriptional profiling, target gene validation, and metabolomics using liquid chromatography-mass spectrometry in order to better characterise ADGRL4/ELTD1s role in endothelial cell biology. We show that ADGRL4/ELTD1 silencing induced expression of the cytoplasmic metabolic regulator ATP Citrate Lyase (ACLY) and the mitochondria-to-cytoplasm citrate transporter Solute Carrier Family 25 Member 1 (SLC25A1) but had no apparent effect on pathways downstream of ACLY (fatty acid and

Purpose: Administration of glucocorticoids (GCs) causes spiking of intraocular pressure in a subset of patients due to a reduction in aqueous outflow facility. GPR158 is expressed in trabecular meshwork (TM) cells of the conventional outflow pathway and transcription is stimulated by GCs (ARVO, Patel et al., 2011). We investigated the possible role of GPR158 in controlling TM cellular activities known to be affected by GCs.. Methods: We used the immortalized TM-1 cell line and primary TM cells isolated from discarded human eye tissue. GPR158 cDNA was cloned into two mammalian expression vectors: pcDNA 3.1(+) and pEGFP-C1, the latter generates C-terminus GFP fusion with GPR158. TM barrier function was quantified using the In Vitro vascular permeability assay , which measures permeability of a confluent cell monolayer to FITC-dextran.. Results: Similar to treatment with GCs, transient overexpression of GPR158 in TM cells increased the rate of cell proliferation (4-fold), and significantly enhanced ...

Dysfunction of the apelinergic system, comprised of the neuropeptide apelin mediating its effects via the G protein-coupled apelin receptor (APJ), may underlie the onset of cardiovascular disease such as hypertension. Apelin expression is increased in the rostral ventrolateral medulla (RVLM) in spontaneously hypertensive rats (SHRs) compared to Wistar-Kyoto (WKY) normotensive rats, however, evidence that the apelinergic system chronically influences mean arterial blood pressure (MABP) under pathophysiological conditions remains to be established. In this study we investigated, in conscious unrestrained rats, whether APJ contributes to MABP and sympathetic vasomotor tone in the progression of two models of hypertension - SHR and L-NAME-treated rats - and whether APJ contributes to the development of hypertension in pre-hypertensive SHR. In SHR we showed that APJ gene (aplnr) expression was elevated in the RVLM, and there was a greater MABP increase following microinjection of [Pyr1]apelin-13 to the RVLM

ENCODES a protein that exhibits trace-amine receptor activity (ortholog); INVOLVED IN sensory perception of chemical stimulus (ortholog); FOUND IN integral component of membrane (inferred); plasma membrane (inferred); INTERACTS WITH 17beta-estradiol; bisphenol A; 2,3,7,8-tetrachlorodibenzodioxine (ortholog)

The KOMP Repository is located at the University of California Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...

The KOMP Repository is located at the University of California Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...

Urotensin-II controls ion/water homeostasis in fish and vascular tone in rodents. We hypothesised that common genetic variants in urotensin-II pathway genes are associated with human blood pressure or renal function. We performed familybased analysis of association between blood pressure, glomerular filtration and genes of the urotensin-II pathway (urotensin-II, urotensin-II related peptide, urotensin-II receptor) saturated with 28 tagging single nucleotide polymorphisms in 2024 individuals from 520 families; followed by an independent replication in 420 families and 7545 unrelated subjects. The expression studies of the urotensin-II pathway were carried out in 97 human kidneys. Phylogenetic evolutionary analysis was conducted in 17 vertebrate species. One single nucleotide polymorphism (rs531485 in urotensin-II gene) was associated with adjusted estimated glomerular filtration rate in the discovery cohort (p = 0.0005). It showed no association with estimated glomerular filtration rate in the ...

GPER/GPR30 is a seven-transmembrane G protein-coupled estrogen receptor that regulates many aspects of mammalian biology and physiology. We have previously described both a GPER-selective agonist G-1 and antagonist G15 based on a tetrahydro-3H-cyclopenta[c]quinoline scaffold. The antagonist lacks an ethanone moiety that likely forms important hydrogen bonds involved in receptor activation. Computational docking studies suggested that the lack of the ethanone substituent in G15 could minimize key steric conflicts, present in G-1, that limit binding within the ER? ligand binding pocket. In this report, we identify low-affinity cross-reactivity of the GPER antagonist G15 to the classical estrogen receptor ER?. To generate an antagonist with enhanced selectivity, we therefore synthesized an isosteric G-1 derivative, G36, containing an isopropyl moiety in place of the ethanone moiety. We demonstrate that G36 shows decreased binding and activation of ER?, while maintaining its antagonist profile ...

CohBars novel CB5064 analogs are agonists of the apelin receptor in vitro and also improve metabolic dysfunction in vivo in obese mice, a known apelin effect, said Kenneth C. Cundy, PhD, CohBars Chief Scientific Officer. In published preclinical studies, apelin signaling demonstrates a key role in protecting animals from acute lung injury and restoring metabolic homeostasis. Our peptides could potentially block many of the acute effects of COVID-19 associated ARDS, and their beneficial effects could extend to protecting other organs from the cytokine storm and reducing mortality in COVID-19 and other forms of acute lung injury.. COVID-19 associated ARDS is a new target for the companys ongoing program of CB5064 analogs. These analogs previously demonstrated efficacy in diet induced obese or DIO mice, a widely used model of type 2 diabetes, leading to significant reduction in body weight, adiposity, and improvement in insulin sensitivity, as presented by CohBar at the American Diabetes ...

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GPRC5B (G protein-coupled receptor class C group 5 member B), Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.

Sex bias in innate defense against Staphylococcus aureus skin and soft tissue infection (SSTI) is dependent on both estrogen production by the host and S. aureus secretion of the virulence factor, α-hemolysin (Hla). The impact of estrogen signaling on the immune system is most often studied in terms of the nuclear estrogen receptors ERα and ERβ. However, the potential contribution of the G protein-coupled estrogen receptor (GPER) to innate defense against infectious disease, particularly with respect to skin infection, has not been addressed. Using a murine model of SSTI, we found that GPER activation with the highly selective agonist G-1 limits S. aureus SSTI and Hla-mediated pathogenesis, effects that were absent in GPER knockout mice. Specifically, G-1 reduced Hla-mediated skin lesion formation and pro-inflammatory cytokine production, while increasing bacterial clearance. In vitro, G-1 reduced surface expression of the Hla receptor, ADAM10, in a human keratinocyte cell line and increased ...

G protein-coupled receptors are a large family of signalling molecules that respond to a wide variety of extracellular stimuli. The receptors relay the information encoded by the ligand through the activation of heterotrimeric G proteins and intracellular effector molecules. To ensure the appropriate regulation of the signalling cascade, it is vital to properly inactivate the receptor. This inactivation is achieved, in part, by the binding of a soluble protein, arrestin, which uncouples the receptor from the downstream G protein after the receptors are phosphorylated by G protein-coupled receptor kinases. In addition to the inactivation of G protein-coupled receptors, arrestins have also been implicated in the endocytosis of receptors and cross talk with other signalling pathways. Arrestin (retinal S-antigen) is a major protein of the retinal rod outer segments. It interacts with photo-activated phosphorylated rhodopsin, inhibiting or arresting its ability to interact with transducin ...

Neuromedin U (NmU) is a neuropeptide involved in various physiological functions such as feeding behavior, muscle contractile activity, and regulation of intestinal ion transport. Recently, two human G protein-coupled receptors have been identified as NmU-specific receptors, NmU-R1 and NmU-R2, which share 55% amino acid identity. It is unclear however, which of the two receptors mediates responses to NmU observed in rodent models. Attempts to define the pharmacological profile of the two receptors are confounded by overlapping expression of the two receptors and a lack of subtype-selective compounds. In order to establish a basis to further our understanding of the function of these receptors, we cloned and characterized the mouse homologues of the two human NmU receptors. Mouse NmU-R1 and mouse NmU-R2 are 79 and 81% identical to their respective human homologues. Expression of NmU-R1 was mainly observed in testis, gastrointestinal (GI) tract, and immune system, while NmU-R2 was primarily expressed in

Dive into the research topics of Possible endogenous agonist mechanism for the activation of secretin family G protein-coupled receptors. Together they form a unique fingerprint. ...

Using NMR spectroscopy, the team mapped the arrangement of atoms in a protein called CXCR1, which detects the inflammatory signal interleukin 8 and, through a G protein located inside the cell, triggers a cascade of events that can mobilize immune cells, for example. Because G protein-coupled receptors are critical for many cellular responses to external signals, they have been a major target for drugs. More precise knowledge of the shapes of these receptors will allow drugmakers to tailor small molecules to better fit specific targets, avoiding collateral hits that can cause detrimental side effects. This finding will have a major impact on structure-based drug development since for the first time the principal class of drug receptors can be studied in their biologically active forms where they interact with other proteins and potential drugs, said Stanley Opella, professor of chemistry and biochemistry at the University of California, San Diego who led the work, which Nature published online October

Numerous studies have demonstrated that females have a higher risk of experiencing several pain disorders with either greater frequency or severity than males. Although the mechanisms that underlie this sex disparity remain unclear, several studies have shown an important role for sex steroids, such as estrogen, in the modulation of nociception. Receptors for estrogen are present in primary afferent neurons in the trigeminal and dorsal root ganglia, and brief exposure to estrogen increases responses to the inflammatory mediator bradykinin (BK). However, the mechanism for estrogen-mediated enhancement of BK signaling is not fully understood. The aim of the present study was to evaluate the relative contributions of estrogen receptor α (ERα), ERβ, and G protein-coupled estrogen receptor 1 (GPER) to the enhanced signaling of the inflammatory mediator BK by 17β-estradiol (17β-E2) in primary sensory neurons from female rats in culture (ex vivo) and in behavioral assays of nociception in vivo. ...

Publications:. Read, C., Nyimanu, D., Williams, T.L., Huggins, D.J., Sulentic, P., Macrae, R.G.C., Yang, P., Glen, R.C., Maguire, J.J. and Davenport, A.P. (2019) International Union of Basic and Clinical Pharmacology. Structure and pharmacology of the apelin receptor with a recommendation that Elabela/Toddler is a second endogenous peptide ligand. Pharmacological Reviews 71(4): 467-502.. Davenport AP, Kleinz M, Lloyd Williams T, Macrae R, Maguire JJ, Nyimanu D, Yang P. Apelin receptor (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database. IUPHAR/BPS Guide to Pharmacology CITE. 2019; 2019(4). Available from: https://doi.org/10.2218/gtopdb/F7/2019.4.. Oral Presentations:. The British Pharmacological Society Pharmacology 2019 Meeting: First application of short hairpin RNA inducible knockdown system to a GPCR to pharmacologically characterise the role of the apelin receptor in hESC derived beating cardiomyocytes.. Posters:. BSCR Autumn Meeting 2019: Generation of a novel inducible ...

The arrest of meiotic prophase in mouse oocytes within antral follicles requires the G protein G s and an orphan member of the G protein-coupled receptor family, GPR3. To determine whether GPR3 activates G s , the localization of Gα s in follicle-enclosed oocytes from Gpr3 +/+ and Gpr3 −/− mice was compared by using immunofluorescence and Gα s GFP. GPR3 decreased the ratio of Gα s in the oocyte plasma membrane versus the cytoplasm and also decreased the amount of Gα s in the oocyte. Both of these properties indicate that GPR3 activates G s . The follicle cells around the oocyte are also necessary to keep the oocyte in prophase, suggesting that they might activate GPR3. However, GPR3-dependent G s activity was similar in follicle-enclosed and follicle-free oocytes. Thus, the maintenance of prophase arrest depends on the constitutive activity of GPR3 in the oocyte, and the follicle cell signal acts by a means other than increasing GPR3 activity ...

Kisspeptins (KiSS-1): Essential Players in Suppressing Tumor Metastasis Kisspeptins;GPR54 receptor;KiSS-1 gene;metastasis;cancer; Kisspeptins (KPs) encoded by the KiSS-1 gene are C-terminally amidated peptide products, including KP-10, KP-13, KP-14 and KP-54, which are endogenous agonists for the G-protein coupled receptor-54 (GPR54). Functional analyses have demonstrated fundamental roles of KiSS-1 in whole body homeostasis including sexual differentiation of brain, action on sex steroids and metabolic regulation of fertility essential for human puberty and maintenance of adult reproduction. In addition, intensive recent investigations have provided substantial evidence suggesting roles of Kisspeptin signalling via its receptor GPR54 in the suppression of metastasis with a variety of cancers. The present review highlights the latest studies regarding the role of Kisspeptins and the KiSS-1 gene in tumor progression and also suggests targeting the KiSS-1/GPR54 system may represent a novel therapeutic

G protein-coupled receptors (GPCRs) in human beings are classified into the five main families named and according to the GRAFS classification. that the fungal receptors do not have N-terminal domains whereas the fungal receptors have a broad repertoire of mammalian-like N-terminal domains. Further, mining of the close unicellular relatives of the Metazoan lineage, and and families, which specifically provided buy Salvianolic acid A insight to the first emergence from the N-terminal domains from the grouped family. We determined 619 Fungi particular GPCRs across 79 genomes and exposed that Blastocladiomycota and Chytridiomycota phylum possess Metazoan-like GPCRs as opposed to the GPCRs particular for Fungi. General, this study supplies the first proof the current presence of four from the five primary GRAFS family members in Fungi and clarifies the first evolutionary background of the GPCR superfamily. Intro G protein-coupled receptors (GPCRs) will be the largest category of transmembrane ...

The development of safe and effective drugs relies on the discovery of selective ligands. Serotonin (5-hydroxytryptamine [5-HT]) G protein-coupled receptors are therapeutic targets for CNS disorders but are also associated with adverse drug effects. The determination of crystal structures for the 5-HT1B and 5-HT2B receptors provided an opportunity to identify subtype selective ligands using structure-based methods. From docking screens of 1.3 million compounds, 22 molecules were predicted to be selective for the 5-HT1B receptor over the 5-HT2B subtype, a requirement for safe serotonergic drugs. Nine compounds were experimentally verified as 5-HT1B-selective ligands, with up to 300-fold higher affinities for this subtype. Three of the ligands were agonists of the G protein pathway. Analysis of state-of-the-art homology models of the two 5-HT receptors revealed that the crystal structures were critical for predicting selective ligands. Our results demonstrate that structure-based screening can ...

Recent pharmacological discovery on trace amine-associated receptor, type 1(TAAR1) has emphasized importance of trace amines in pathogenesis of psychoses, such as schizophrenia. TAAR1 has many ligands, including tyramine, β-phenylethylamine (PEA), amphetamines, and 3-iodothyronamine. So-called D-neurons are putative producer of trace amines, endogenous ligands of TAAR1. The D-neuron is defined

Background Metastasis is a process by which tumors spread from primary organs to other sites in the body and is the major cause of death for cancer patients. The ovarian cancer G protein-coupled receptor 1 (OGR1) gene has been shown to be expressed at lower levels in metastatic compared with primary prostate cancer tissues. Methods We used an orthotopic mouse metastasis model, in which we injected PC3 metastatic human prostate cancer cells stably transfected with empty vector (vector-PC3) or OGR1-expressing vector (OGR1-PC3) into the prostate lobes of athymic or NOD/SCID mice (n = 3-8 mice per group). Migration of PC3 cells transiently transfected with vector control or with OGR1- or GPR4 (a G protein-coupled receptor with the highest homology to OGR1)-expressing vectors was measured in vitro by Boyden chamber assays. G protein alpha-inhibitory subunit 1 (Gα i1 ) expression after treatment with pertussis toxin (PTX) was measured using immunoblotting analysis. The inhibitory factor present in the

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cdna:known chromosome:VEGA66:10:23970706:23971719:1 gene:OTTMUSG00000019210 gene_biotype:protein_coding transcript_biotype:protein_coding gene_symbol:Taar5 description:trace amine-associated receptor 5 ...

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G protein-coupled receptors (GPCRs) are the largest family of integral membrane proteins and a major class of drug targets. Membranes are known to have modulatory effects on GPCRs via specific lipid interactions. However, the mechanisms of such modulations in cell membranes and how they influence GPCR functions remain unclear. Here we report coarse-grained MD simulations on the Adenosine A2a receptor embedded in an in vivo mimetic membrane model comprised of 10 different lipid species. Three conformational states of the receptor, i.e. the inactive state, the active state, and the active state with a mini-GS protein bound were simulated to study the impact of protein-lipid interactions on the receptor activation. The simulations revealed three specific lipids (GM3, cholesterol and PIP2) that form stable and preferential interactions with the receptor, differentiating these from bulk lipids such as PS, PE and PC. In total, nine specific lipid-binding sites were revealed. The strength of lipid interaction