Chemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and Processes
Gene Expression ProfilingGTP-Binding Protein alpha Subunits, Gi-GoPertussis ToxinGTP-Binding ProteinsPhosphorylationVirulence Factors, BordetellaAdenylate Cyclase Toxin
GPCRsPathwaysLigandOrphan G-protein-Cell surface rAgonistsSeven-transmembranePhosphorylationChemokineKinasesProteinsAdrenergicMetabotropicDopamine D2 receptorGuanylate cyclaseModulate receptorSIGNAL TRANSDUCTIONOlfactoryExtracellularGPERSignalingIntracellularGPR161GenePhysiologicalMammalianOverexpressionGenesPathophysiologyFunctionalCharacterizationAgonismAllostericSpecificityCCR5FamilyInitiateMechanismsSubject HeadingsNeuroscienceExpressionPeptidePathway
GPCRs10
  • G-protein-coupled receptors (GPCRs) modulate many physiological processes by transducing a variety of extracellular cues into intracellular responses. (nih.gov)
  • The G protein-coupled receptor (GPCR) kinases (GRKs) phosphorylate and desensitize agonist-occupied GPCRs. (duke.edu)
  • Background G-protein-coupled receptors (GPCRs) play an essential role in lots of natural processes and represent a significant class of drug targets. (exposed-skin-care.net)
  • Furthermore, pre-exposure of GPCR transgenic pets to its ligand prospects to receptor desensitisation and behavioural version to following ligand publicity, providing further proof integration from the mammalian GPCRs in to the em C. elegans /em sensory signalling equipment. (exposed-skin-care.net)
  • Therefore, we attempt to check whether we'd elicit ligand-dependent behavioural reactions in em C. elegans /em by expressing mammalian GPCRs in the ASH and ADL gustatory neurons, because they are straight exposed to the surroundings allowing gain access to of proteins and peptide ligands towards the heterologous receptors. (exposed-skin-care.net)
  • Because they are involved in so many physiological processes, G protein coupled receptors (GPCRs) are engaged by roughly 40% of marketed drugs and remain a prime target for the development of new therapeutics. (cqdm.org)
  • The recent increase in the number of X-ray crystal structures of G-protein coupled receptors (GPCRs) has been enabling for structure-based drug design (SBDD) efforts. (upf.edu)
  • For meaningful results, all protein classes have to be tractable, including G protein-coupled receptors (GPCRs). (centogene.com)
  • G-protein-coupled receptors (GPCRs), the largest family of transmembrane proteins, are widespread and play important roles in the nervous system. (grantome.com)
  • Glutamate interacts with metabotropic glutamate receptors (mGluRs), and GABA with GABAB receptors (GABABRs), both of which are GPCRs. (grantome.com)
Pathways7
  • Kim JY, Haastert PV, Devreotes PN (1996) Social senses: G-protein-coupled receptor signaling pathways in Dictyostelium discoideum . (springer.com)
  • We showed that receptor pathways mediated by Gs-coupling were regulated through a strictly phosphorylation-dependent process, while Gq-mediated signalling could be modulated in a phosphorylation-independent way. (open.ac.uk)
  • Multiple endocytic pathways of G protein-coupled receptors delineated by GIT1 sensitivity. (duke.edu)
  • Receptors transduce these signals to alter intracellular metabolism and cellular responsiveness through heterotrimeric G protein/second messenger pathways or through small GTP-binding protein/protein kinase cascades. (duke.edu)
  • Receptors and signaling pathways evaluated were selected for their potential therapeutic value as targets for cancer as well as neurologic disease. (cqdm.org)
  • When activated, these receptors initiate a multitude of signaling transduction pathways important in mediating modulation of neuronal excitability and synaptic transmission (one of the major ways cells communicate with each other). (grantome.com)
  • Adaptations of receptor-coupled signal transduction pathways underlying stress and drug-induced neuronal plasticity. (bvsalud.org)
Ligand11
  • GPRs are cell surface receptors that activate guanine-nucleotide binding proteins upon the binding of a ligand. (nih.gov)
  • The protein encoded by this gene is an orphan G protein-coupled receptor whose ligand is unknown. (nih.gov)
  • Ligand binding to an extracellular orthosteric pocket propagates conformational change to the receptor cytosolic region to promote binding and activation of downstream signalling effectors such as G proteins and β-arrestins. (nih.gov)
  • Assessing the binding of 17 ligands of varying efficacy to the β2AR in the absence and presence of Nb60 or Nb80 reveals large ligand-specific effects that can only be explained using an allosteric model which assumes equilibrium amongst at least three receptor states. (nih.gov)
  • Recent studies propose that N-arachidonyl glycine (NAGly), a carboxylic analogue of anandamide, is an endogenous ligand of the Gα(i/o) protein-coupled receptor 18 (GPR18). (unboundmedicine.com)
  • We have used the pheromone alpha-factor receptor (Ste2p) of the yeast Saccharomyces cerevisiae as a model system to understand ligand binding, receptor activation, and G protein interaction. (tennessee.edu)
  • Some residues were found to be in close proximity and displayed different interacting patterns due to conformational changes of the receptor upon ligand binding. (tennessee.edu)
  • The information we gathered here allows us to understand more about the physical interactions of alpha-factor, Ste2p, and Gpa1p and provides us insights about the initiation and activation of the signal transduction pathway of a peptide ligand receptor. (tennessee.edu)
  • Using em C. elegans /em to review em in vivo /em GPCR-ligand connections is an benefit because functional appearance of heterologous olfactory receptors in the AWA and AWB olfactory neurons provides previously been proven (Milani em et al /em ) [5] and our unpublished observations. (exposed-skin-care.net)
  • The nociceptive neurons, ASH and ADL, travel repulsive reactions, [6] therefore receptor activation is usually reflected within an avoidance response on ligand publicity, which may be analysed using strong behavioural assays [7,8]. (exposed-skin-care.net)
  • When a ligand binds to these membrane-bound receptor proteins, the receptor activates intermediate proteins called G-proteins. (neuroscientificallychallenged.com)
Orphan G-protein-1
  • Cloning and characterization of a novel orphan G-protein-coupled receptor localized to human chromosome 2p16. (nih.gov)
Cell surface r2
  • The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. (harvard.edu)
  • Critical physiological events throughout the body are controlled by extracellular signals from neurotransmitters and hormones acting on cell surface receptors. (duke.edu)
Agonists5
  • However, how agonists with varying efficacy modulate these receptor states to initiate cellular responses is not well understood. (nih.gov)
  • Agonists generally exert efficacy by stabilizing the active Nb80-stabilized receptor state (R80). (nih.gov)
  • In contrast, for a number of partial agonists, both stabilization of R80 and destabilization of the inactive, Nb60-bound state (R60) contribute to their ability to modulate receptor activation. (nih.gov)
  • R&D Systems offers antibodies for the receptors listed below, as well as agonists for the cannabinoid receptors. (rndsystems.com)
  • For example, beta-agonists, the rescue medication inhaled by asthmatics, act at airway smooth muscle beta2-adrenergic receptors (β2-AR) to relax the airways. (duke.edu)
Seven-transmembrane2
  • Violin JD, Lefkowitz RJ (2007) Beta-arrestin-biased ligands at seven-transmembrane receptors. (springer.com)
  • Mutational analysis and chimeric constructs have revealed that allosteric modulators of the calcium-sensing, metabotropic glutamate and GABA B receptors bind to the seven transmembrane domain, through which they modify signal transduction after receptor activation. (aspetjournals.org)
Phosphorylation2
  • GRK2-mediated receptor phosphorylation is preceded by the agonist-dependent membrane association of this enzyme. (duke.edu)
  • These results show that in mesenteric arteries an intact cytoskeleton and force development are not prerequisites for G-protein-coupled receptor-induced activation of PYK2 and paxillin, by tyrosine phosphorylation, in vascular tissue, but are necessary for the translocation of PYK2 and paxillin to the membrane. (manchester.ac.uk)
Chemokine3
  • CCR5 is usually a chemokine receptor that binds MIP-1 (CCL3), MIP-1 (CCL4) and RANTES, and directs chemotactic reactions in leucocytes. (exposed-skin-care.net)
  • SUMMARY A direct correlation between HIV infection and mutation in the chemokine receptor ( CCR5 ) gene has been established. (who.int)
  • HIV-1 is influenced by a mutation in the 1 infection with a typical delay of 2-4 years chemokine receptor ( CCR5 ) gene [ 3,4 ]. (who.int)
Kinases4
  • Key molecular determinants of this process are G protein-coupled receptor kinases (GRKs) and arrestins (Chuang, 1996a). (open.ac.uk)
  • This protein initially was identified as an interacting partner for the G protein-coupled receptor kinases, and its overexpression was found to affect signaling and internalization of the prototypical beta(2)-adrenergic receptor. (duke.edu)
  • Monoclonal antibodies reveal receptor specificity among G-protein-coupled receptor kinases. (duke.edu)
  • Receptor and G betagamma isoform-specific interactions with G protein-coupled receptor kinases. (duke.edu)
Proteins7
  • Guanylate cyclase-coupled receptors or Membrane-bound guanylyl cyclases are single-pass transmembrane proteins. (wikipedia.org)
  • Sequence comparison does not support an evolutionary link between halobacterial retinal proteins including bacteriorhodopsin and eukaryotic G-protein-coupled receptors. (springer.com)
  • Mutants of GPR18, designed to constitutively activate receptors, did not tonically inhibit calcium currents, indicating a lack of GPR18 activation or coupling to endogenous G proteins. (unboundmedicine.com)
  • Furthermore, GPR18 did not couple to other G proteins tested: Gα(s), Gα(z), and Gα(15). (unboundmedicine.com)
  • The signal transduction pathway of the receptor starts from sensing outside signal and then activates G proteins. (tennessee.edu)
  • however, Fz proteins constitute a distinct group within the GPCR (G-proteincoupled receptor) superfamily, and Fz signalling can be G-proteinindependent in some experimental setups, leading to concerns about the GPCR nature of these proteins. (uni-konstanz.de)
  • These responses were sensitive to a Wnt antagonist and to pertussis toxin, which decouples the Go/i proteins from their receptors through covalent modification. (uni-konstanz.de)
Adrenergic4
  • Furthermore, increasing biophysical evidence, primarily using the β2-adrenergic receptor (β2AR) as a model system, supports the existence of multiple active and inactive conformational states. (nih.gov)
  • In patients with infection-triggered onset, the associations of low sCD26 with elevated autoantibodies (AAB) against alpha1 adrenergic (AR) and M3 muscarinic acetylcholine receptors (mAChR) point to a pathomechanism of infection-triggered autoimmune-mediated vascular and immunological dysregulation. (frontiersin.org)
  • Autoantibodies (AAB) against nuclear and membrane structures as well as neurotransmitter receptors including muscarinic cholinergic receptor M3/M4-antibodies (M3-mAChR/M4-mAChR) and beta-1 and -2-adrenergic receptor (beta1-AR/beta2-AR) have been described in patients with ME/CFS ( 3 , 6 - 8 ). (frontiersin.org)
  • These antibodies belong to a network of natural antibodies against adrenergic, cholinergic and other G-protein coupled receptors (GPCR) which were shown to be dysregulated and dysfunctional in various autoimmune diseases ( 9 ). (frontiersin.org)
Metabotropic2
  • aka metabotropic receptor or GPCR. (neuroscientificallychallenged.com)
  • The results of this work will further our understanding of how metabotropic receptors contribute to auditory signal processing/temporal coding, and help lay the groundwork for decisions about possible therapeutic approaches to hearing defects related to altered synaptic transmission, such as dyslexia, tinnitus, and age-related hearing loss. (grantome.com)
Dopamine D2 receptor1
  • We synthesized CCs with sertindole attached to the CC scaffold in different orientations to target the dopamine D2 receptor (DRD2) heterologously expressed in HEK 293 cells. (centogene.com)
Guanylate cyclase4
  • Guanylate cyclase-coupled receptor on cell surface consists of two parts: the extracellular part, or the receptor domain, and the intracellular part, or the guanylate cyclase activity domain. (wikipedia.org)
  • An example of Guanylate cyclase-coupled receptors is ANF receptors (NPR1, NPR2 and NPR3) in kidney. (wikipedia.org)
  • Additionally, there exist intracellular guanylate cyclase-coupled receptor like soluble NO-activated guanylate cyclase. (wikipedia.org)
  • A class of cellular membrane receptors that either have an intrinsic guanylate cyclase activity or are closely coupled to specific guanylate cyclases within the cell. (bvsalud.org)
Modulate receptor1
  • Allosteric ligands modulate receptor function by binding to a site distinct from the recognition site for the endogenous agonist. (aspetjournals.org)
SIGNAL TRANSDUCTION1
  • Receptor Signal Transduction Protocols (pp. 237-249). (brighton.ac.uk)
Olfactory5
  • It is a specialized pseudostratified neuroepithelium containing the primary olfactory receptors. (medscape.com)
  • The sense of smell is mediated through stimulation of the olfactory receptor cells by volatile chemicals. (medscape.com)
  • To stimulate the olfactory receptors, airborne molecules must pass through the nasal cavity with relatively turbulent air currents and contact the receptors. (medscape.com)
  • Odorants can also be perceived by entering the nose posteriorly through the nasopharynx to reach the olfactory receptor via retronasal olfaction. (medscape.com)
  • Odorants diffuse into the mucous and are transported to the olfactory receptor. (medscape.com)
Extracellular1
  • Family C G-protein-coupled receptors are characterized by a large extracellular domain containing the orthosteric agonist binding site known as the "venus flytrap module" because of its bilobal structure and the dynamics of its activation mechanism. (aspetjournals.org)
GPER1
  • Ischemic stroke increases membrane-bound G protein-coupled estrogen receptor (GPER) distribution and expression in the brain of male but not female mice. (monash.edu)
Signaling5
  • GPR75 receptor mediates 20-HETE-signaling and metastatic features of androgen-insensitive prostate cancer cells. (nih.gov)
  • G-protein-coupled receptor signaling and neural tube closure defects. (nih.gov)
  • Other downstream effectors of Gα(i/o)-coupled receptors, G protein-coupled inwardly rectifying potassium channels and adenylate cyclase, were not modulated by GPR18 signaling. (unboundmedicine.com)
  • Thus, GIT1 is a protein involved in regulating the function of signaling receptors internalized through the clathrin pathway and can be used as a diagnostic tool for defining the endocytic pathway of a receptor. (duke.edu)
  • Coupled Receptor Signaling in Renin-Producing Cells Leads to Renal Endothelial Damage. (bvsalud.org)
Intracellular1
  • We also showed that PAF could stimulate intracellular cAMP accumulation in lymphocytes, suggesting that PAFR-coupling with adenylyl cyclase may be important also for endogenously expressed receptors. (open.ac.uk)
GPR1611
  • G-protein-coupled receptor GPR161 is overexpressed in breast cancer and is a promoter of cell proliferation and invasion. (nih.gov)
Gene3
  • In all cases, we discovered pathogenic mutations in P2RY5 , which encodes a G protein-coupled receptor and is a nested gene residing within intron 17 of the retinoblastoma 1 ( RB1 ) gene. (nature.com)
  • Genetic drift and selective forces have shaped the individual structure of a given receptor gene but also of the species-specific receptor repertoire - a process that is still ongoing. (springer.com)
  • The protein encoded by P2RY8 gene is composed of 359-amino acids and belongs to the P2Y family of G-protein coupled receptors that are preferentially activated by adenosine and uridine nucleotides. (atlasgeneticsoncology.org)
Physiological2
  • They often have no effect on their own and therefore act only in conjunction with physiological receptor activation. (aspetjournals.org)
  • These new tools (FRET biosensors) and promising models (knock-in mice) enable physiological and directly detectable expression of the targeted receptor and/or effector protein. (cqdm.org)
Mammalian1
  • There are eight mammalian P2Y receptors known to date ( P2Y1 , P2Y2 , P2Y4 , P2Y6 , P2Y11 , P2Y12 , P2Y13 and P2Y14 ) and they are found in most human tissues. (atlasgeneticsoncology.org)
Overexpression2
  • Here, we report that GIT1 overexpression regulates internalization of numerous, but not all, G protein-coupled receptors. (duke.edu)
  • Furthermore, the GIT1 effect is not limited to G protein-coupled receptors because overexpression of this protein also affects internalization of the epidermal growth factor receptor. (duke.edu)
Genes3
  • False positive non-synonymous polymorphisms of G-protein coupled receptor genes. (nih.gov)
  • The valuable source of large-scale genomic information initiated attempts to identify the origin(s) of G protein-coupled receptors (GPCR), count and categorize those genes, and follow their evolutionary history. (springer.com)
  • The chapter summarizes evolutionary processes working on GPCR genes and sheds light on their consequences at the levels of receptor structure and function. (springer.com)
Pathophysiology1
  • Broadly, my research focuses on the role for G protein-coupled receptors in the pathophysiology of asthma. (duke.edu)
Functional1
  • also known as the thymic stromal lymphopoietin receptor), which together with IL7 receptor alpha forms a heterodimeric complex that acts at the functional receptor for thymic stromal lymphopoietin (reviewed in Roll and Reuther, 2010). (atlasgeneticsoncology.org)
Characterization2
  • Robben, J.H., Knoers, N.V. & Deen, P.M. Characterization of vasopressin V2 receptor mutants in nephrogenic diabetes insipidus in a polarized cell model. (nature.com)
  • There is however a practical limit to the amount of energy which can be applied, which often precludes subsequent characterization by top-down MS. To overcome this barrier, we have applied a modified Orbitrap Eclipse Tribrid mass spectrometer coupled to an infrared laser within a high-pressure linear ion trap. (fu-berlin.de)
Agonism1
  • Allosteric receptor modulation is an attractive concept in drug targeting because it offers important potential advantages over conventional orthosteric agonism or antagonism. (aspetjournals.org)
Allosteric2
  • This article reviews the current status of allosteric modulation at family C G-protein coupled receptors in the light of their specific structural features on the one hand and current concepts in receptor theory on the other hand. (aspetjournals.org)
  • The positive allosteric calcium sensing receptor modulator cinacalcet is the first drug of this type to enter the market and therefore provides proof of principle in humans. (aspetjournals.org)
Specificity1
  • The specificity of the GIT1 effect is not related to the type of G protein to which a receptor couples, but rather to the endocytic route it uses. (duke.edu)
CCR51
  • CCR5 also serves as an entry co-receptor der the age of 15. (who.int)
Family3
  • GPR75 is a member of the G protein-coupled receptor family. (nih.gov)
  • The G protein-coupled receptor (GPCR) family is composed of hundreds of members and is expressed in eukaryotes. (tennessee.edu)
  • Receptors of the Fz (Frizzled) family initiate Wnt liganddependent signalling controlling multiple steps in organism development and carcinogenesis. (uni-konstanz.de)
Initiate1
  • These data demonstrate that ligands can initiate a wide range of cellular responses by differentially stabilizing multiple receptor states. (nih.gov)
Mechanisms1
  • Mechanisms whereby these receptors improve temporal processing in hearing will be revealed at cellular and molecular levels. (grantome.com)
Subject Headings1
  • Receptors, G-Protein-Coupled" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (harvard.edu)
Neuroscience1
Expression1
  • Proper expression and trafficking of receptor were confirmed by the "rim-like" fluorescence of fluorescently tagged receptor and the positive staining of external hemagglutinin-tagged GPR18-expressing cells. (unboundmedicine.com)
Peptide1
  • Human epicardial adipose tissue expresses glucose-dependent insulinotropic polypeptide, glucagon, and glucagon-like peptide-1 receptors as potential targets of pleiotropic therapies. (harvard.edu)
Pathway1
  • GIT1 only affects the function of G protein-coupled receptors that are internalized through the clathrin-coated pit pathway in a beta-arrestin- and dynamin-sensitive manner. (duke.edu)