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 ...
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 ...
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
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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 ...
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 ...
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 ...
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 ...
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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 ...
Tarttelin EE, Kirschner LS, Bellingham J, Baffi J, Taymans SE, Gregory-Evans K, Csaky K, Stratakis CA, Gregory-Evans CY (Jul 1999). "Cloning and characterization of a novel orphan G-protein-coupled receptor localized to human chromosome 2p16". Biochem Biophys Res Commun 260 (1): 174-80. PMID 10381362. doi:10.1006/bbrc.1999.0753. Cite uses deprecated parameter ...
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 ...
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
Over the past several years tumor necrosis factor (TNF) antagonists have become first-line agents in the treatment of moderate-to-severe psoriasis. and vascular abnormalities [1]. Although the exact etiology of psoriasis remains unclear current evidence indicates that it is T-cell driven. Individuals with active skin disease have elevated levels Freselestat of tumor necrosis element alpha (TNFα) in both blood and lesional pores and skin [2]. TNFα which is definitely secreted by both T cells and antigen-presenting cells within lesional pores and skin has emerged as a key mediator in the disease process. Specifically TNFα is definitely a pro-inflammatory cytokine that amplifies swelling through several unique pathways: facilitating access of inflammatory cells into lesional pores and skin through induction of adhesion molecules on vascular endothelial cells; stimulating keratinocyte production of additional pro-inflammatory mediators [3]; and finally activating dermal macrophages and dendritic ...
Omeros Corporation (NASDAQ: OMER) today reported that it has identified compounds that interact with orphan G protein-coupled receptors (GPCRs) GPR27 and GPR173.
Title:Application of BRET for Studying G Protein-Coupled Receptors. VOLUME: 14 ISSUE: 5. Author(s):Agnieszka A. Kaczor, Magdalena Makarska-Bialokoz, Jana Selent, Rocio A. de la Fuente, Maria Marti-Solano and Marian Castro. Affiliation:Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Lab, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4A Chodzki St., PL-20093 Lublin, Poland.. Keywords:BRET, G protein-coupled receptors, G protein-coupled receptor dimers.. Abstract:G protein-coupled receptors (GPCRs) constitute one of the largest classes of cell surface receptors. GPCR biology has been a subject of widespread interest owing to the functional relevance of these receptors and their potential importance in the development of new drugs. At present, over 30% of all launched drugs target these receptors. GPCRs have been considered for a long time to function as monomeric entities and the idea of GPCR dimerization ...
The protein encoded by this gene is a member of the G protein-coupled receptor family; however, the specific function of this gene has not yet been determined.
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Smooth muscle (SM) tissue is a complex organization of multiple cell types and is regulated by numerous signaling molecules (neurotransmitters, hormones, cytokines, etc.). SM contractile function can be regulated via expression and distribution of the contractile and cytoskeletal proteins, and activation of any of the second messenger pathways that regulate them. Spatial-temporal changes in the contractile, cytoskeletal or regulatory components of SM cells (SMCs) have been proposed to alter SM contractile activity. Ca2+ sensitization/desensitization can occur as a result of changes at any of these levels, and specific pathways have been identified at all of these levels. Understanding when and how proteins can translocate within the cytoplasm, or to-and-from the plasmalemma and the cytoplasm to alter contractile activity is critical. Numerous studies have reported translocation of proteins associated with the adherens junction and G protein-coupled receptor activation pathways in isolated SMC systems.
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 ...
Degeneration of retinal photoreceptor cells can arise from environmental and/or genetic causes. Since photoreceptor cells, the retinal pigment epithelium (RPE), neurons and glial cells of the retina are intimately associated; all cell types eventually are affected by retinal degenerative diseases. Such diseases often originate either in rod and/or cone photoreceptor cells or the RPE. Of these, cone cells located in the central retina are especially important for daily human activity. Here we describe the protection of cone cells by a combination therapy consisting of the G protein-coupled receptor modulators metoprolol, tamsulosin, and bromocriptine. These drugs were tested in Abca4-/-Rdh8-/- mice, a preclinical model for retinal degeneration. The specificity of these drugs was determined with an essentially complete panel of human G protein-coupled receptors. Significantly, the combination of metoprolol, tamsulosin, and bromocriptine had no deleterious effects on electroretinographic responses ...
Obesity and type 2 diabetes are two concomitant metabolic disorders. Type 2 diabetes is a complex heterogeneous disease, and the number of patients continues to grow. Insulin resistance is a key cause of type 2 diabetes, and obesity is the main cause to produce insulin resistance.. For most patients with type 2 diabetes, insulin resistance and insulin secretion decrease exist simultaneously, which is the main pathophysiological mechanism.. G protein-coupled receptor with seven transmembrane ability is a common target for many therapeutic drugs. G protein-coupled receptors can affect insulin activity, insulin secretion and elongation of beta cells. Therefore, specific G protein-coupled receptors become potential drug targets for anti-diabetic therapy.. Insulin resistance. Leukotriene B4 (LTB4). Free fatty acid receptor 4 (FFAR4). Insulin secretion decrease. GLP1 receptor. It is generally believed that GLP1R agonists exert anti-diabetic effects mainly through three mechanisms:. 1. GLP1R is ...
G Protein-coupled Receptors - Molecular Pharmacology provides a clear summary of the current knowledge in this fast-evolving field. The book sets out with an introduction tosignalling molecules and their receptors, and an overview of the technical approaches used to investigate these interactions. Structural, functional and especially pharmacological aspects of GPCRs are then discussed in more detail and much attention is devoted to the analysis and interpretation of experimental data. The now widespread use of recombinant cell lines, receptor mutants and related artifices in drug research is critically evaluated. Special attention is also devoted to topical but often poorly understood concepts, such as insurmountable antagonism, inverse agonism and allosteric interactions. By combining general information with the major state-of-the-art concepts in GPCR research, the book equips the reader with the necessary background for understanding and critically evaluating the current literature ...
GPCR-mediated growth suppression has been previously described for the platelet-activating factor receptor, which can promote G0 exit and inhibit the G1 to S transition in a ligand-dependent manner. Activation of the platelet-activating factor receptor can block v-Src and v-Ras induced oncogenic morphological changes and anchorage-independent growth (64). Binding of the yeast α-mating factor to its receptor Ste2 induces a G1 arrest via a cyclin-dependent kinase inhibitor FAR1 (65-67). Induction of G2A by oncogenic signals and DNA damage and the ability of G2A to antagonize these signals suggest that G2A functions like a tumor suppressor gene. This is consistent with our data showing that forced overexpression of G2A is counter-selected over time in lymphocyte cell populations, and the loss of G2A expression correlates with enhanced transformation by BCR-ABL in pre-B cells.. The ligands of GPCRs are extremely diverse, ranging from small biogenic amines to large glycoprotein hormones. Signature ...
GPR63 - GPR63 (GFP-tagged) - Human G protein-coupled receptor 63 (GPR63), transcript variant 1 available for purchase from OriGene - Your Gene Company.