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Signal TransductionLigandsTransduction, GeneticProtein Sorting SignalsMolecular Sequence DataAmino Acid SequencePhosphorylationCell LineCells, CulturedBase SequenceProtein BindingMutationEnzyme ActivationModels, BiologicalTransfectionBinding SitesProtein Structure, TertiaryProtein-Tyrosine KinasesCD40 LigandRecombinant Fusion ProteinsMembrane ProteinsRNA, MessengerTyrosineTranscription FactorsRecombinant ProteinsMitogen-Activated Protein KinasesKineticsReceptors, Cell SurfaceDNA-Binding ProteinsFas Ligand ProteinCalciumSequence Homology, Amino AcidGene Expression RegulationCell MembraneProteinsBacterial ProteinsTumor Cells, CulturedModels, MolecularProtein Kinase CProtein KinasesAdaptor Proteins, Signal TransducingProtein-Serine-Threonine KinasesEnzyme InhibitorsGenetic VectorsTranscription, GeneticCarrier ProteinsPhosphoproteinsMembrane GlycoproteinsBlotting, WesternGene ExpressionCloning, MolecularGTP-Binding ProteinsApoptosisCell DivisionIntracellular Signaling Peptides and ProteinsProto-Oncogene ProteinsMice, Inbred C57BLTime FactorsCyclic AMPType C PhospholipasesCOS CellsMAP Kinase Signaling SystemCell DifferentiationPhosphatidylinositol 3-KinasesCalcium-Calmodulin-Dependent Protein KinasesReceptors, G-Protein-CoupledCell Line, TumorProtein ConformationMutagenesis, Site-DirectedDNA, ComplementaryReverse Transcriptase Polymerase Chain ReactionTrans-Activators3T3 CellsCricetinaePeptidesDose-Response Relationship, DrugCHO CellsStructure-Activity RelationshipProtein TransportCytoplasmEscherichia coliPromoter Regions, GeneticT-LymphocytesSequence AlignmentMice, KnockoutCell NucleusPhosphotyrosinePhenotypeNF-kappa BAntigens, CDSecond Messenger SystemsGene Expression Regulation, BacterialMitogen-Activated Protein Kinase 1Green Fluorescent ProteinsGene Expression Profilingras ProteinsChemotaxisArabidopsisGene Expression Regulation, PlantReceptors, Antigen, T-Cell
ReceptorsPathwayPathwaysProteinsReceptor TyrosinKinaseCascadesIntracellularInteractionTranscriptionalProteinMoleculesDownstreamDifferentiationMAPKMechanismDimericExtracellularEffectorConcentrationsCellularKineticsEncodesVivoRTKsHomeostasisOccursInvolvesBiologicalNotchSensoryCancerMolecularRevealsImmuneRelationRoleGrowthCellsData
Receptors21
  • SR1001 binds specifically to the ligand-binding domains of RORα and RORγt, inducing a conformational change within the ligand-binding domain that encompasses the repositioning of helix 12 and leads to diminished affinity for co-activators and increased affinity for co-repressors, resulting in suppression of the receptors' transcriptional activity. (nature.com)
  • This third edition continues to combine current understanding of classical quantitative pharmacology and drug-receptor interactions with the basics of receptor structure and signal transduction mechanisms, providing an integrated analysis of the mechanisms of drug action at membrane receptors. (routledge.com)
  • Maintaining the second edition's focus on cell membrane receptors and the immediate signal transduction events at the membrane, this edition includes updated chapters on receptor structure and signal transduction by G-proteins and tyrosine kinases as well as enhancements to the quantitative treatment of drug-receptor interactions. (routledge.com)
  • His current major research interests are N-methyl-D-aspartate (NMDA) receptors in the stubstantia nigra in relation to cell death in Parkinson's disease and also ion transport and signaling in mast cells in relation to intracellular pH and volume regulation. (routledge.com)
  • we therefore tested for cannabinoid receptors in seven representative species, using tritiated ligand binding assays with [3H]CP55,940 displaced by the CB1-selective antagonist SR141716A. (researchgate.net)
  • Family A receptors (EPHA) and ligands (EFNA) can act as oncogenes or tumor suppressors and are implicated in chemoresistance. (hindawi.com)
  • Ephrins, also known as ephrin ligands, and Eph receptors (Ephs), which are RTKs, are key regulators of physiological and pathological processes involved in development and disease, such as cellular motility, cell repulsion, and cell adhesion [ 4 ]. (hindawi.com)
  • Both receptors and ligands are membrane-bound proteins that require direct cell-cell interaction for activation. (hindawi.com)
  • The receptors are also categorized as A or B according to the type of ligand they bind to. (hindawi.com)
  • Ephrin family A includes ten receptors named EPHA (1-10) and five ligands designated as EFNA (1-5) [ 6 ]. (hindawi.com)
  • The interaction between ligands and receptors via bidirectional signaling and its involvement in cancer biology are mediated by complex processes [ 7 , 8 ]. (hindawi.com)
  • Here we discuss the history of the study of adenosine receptor ligands for asthma and how enhanced understanding of adenosine receptor biology may aid in the rational exploitation of these receptors as therapeutic targets. (jci.org)
  • ATP, released by cells, is rapidly metabolized by extracellular nucleotidases to adenosine, a potent signaling molecule that can activate several cell surface receptors to produce myriad effects on both parenchymal and immune cells throughout the body (Figure 1 ). (jci.org)
  • Moreover, many of these channels are receptors for ligands that elicit distinct psychophysical sensations, such as the heat associated with capsaicin and the cold felt with menthol. (nih.gov)
  • The cytokine family operates through a common theme of binding private receptors for each ligand before engaging the common γ c receptor to induce signaling. (biorxiv.org)
  • Growth factors (also known as trophic factors) bind to cell-surface receptors to initiate signaling pathways that result in the growth and differentiation of numerous different cell types. (tocris.com)
  • New PET radiotracers are synthesized for use as in vivo ligands to measure many different molecular targets, including membrane-bound receptors, proteins associated with intracellular signal transduction, and ones that reflect gene expression. (nih.gov)
  • b ) receptors that associate with other tyrosine kinases, and ( c ) tyrosine-kinase-associated receptors with the ligand-binding subunit membrane anchored by a glycolipid, such as that for ciliary neurotrophic factor. (aspetjournals.org)
  • Extracellular ATP has been reported to mediate excitation of sensory neurons via P2X receptors, which are ligand-gated ion channels. (jneurosci.org)
  • Burnstock (1999) recently put forward a hypothesis about purinergic mechanosensory transduction that proposed that in hollow organs, including the ureter and bladder, distension causes release of ATP from epithelial cells lining these organs and that ATP can then activate P2X 3 receptors on subepithelial sensory nerve terminals to evoke neural discharge. (jneurosci.org)
  • JAK2 is a member of the class I type tyrosine kinase family of enzymes and is involved in signal transduction for erythropoietin , thrombopoietin, and granulocyte colony-stimulating factor (G-CSF) receptors among other entities. (msdmanuals.com)
Pathway6
  • The Notch receptor is part of a core signalling pathway which is highly conserved in all metazoan species. (nih.gov)
  • On the other hand, PQQ did not inhibit the signaling pathway from RANK/RANKL binding to NFATc1 activation, including NF-κB and mitogen-activated protein kinases (MAPKs). (nih.gov)
  • This signal transduction pathway is initiated by epidermal growth factor ligands binding to and activating receptor tyrosine kinases (RTK) at the cell membrane. (hindawi.com)
  • ROR2 functions primarily through the Wnt signaling pathway [ 12 ]. (oncotarget.com)
  • Here we report a role for the phylogenetically ancient mitogen-activated protein kinase (MAPK) signalling pathway in mouse sex determination. (plos.org)
  • This mutant, which we called boygirl ( byg ), was shown to contain an early stop codon that disrupts the autosomal gene encoding MAP3K4, a component of the mitogen-activated protein kinase (MAPK) signaling pathway. (plos.org)
Pathways6
  • Genetically engineered CID systems are used in biological research to control protein localization, to manipulate signalling pathways and to induce protein activation. (wikipedia.org)
  • Western blot of retinal tissue three days following optic nerve crush compared to uninjured control: upregulation of injury marker, pcJun, demonstrates activation of signaling pathways important for neuronal outcome following ONC. (pharmoptima.com)
  • Immunostained whole mount retinas following optic nerve crush (ONC): upregulation of injury marker, pcJun, demonstrates activation of injury signaling pathways resulting in retinal ganglion cell (RGC) death following ONC. (pharmoptima.com)
  • Although growth factors act on different cell types, the signal pathways they initiate often overlap: for example, both EGF and FGF ensure cell survival by activating PI 3-K and MAPK cascades. (tocris.com)
  • Key signaling pathways are highlighted, and the regulation of ES cell self-renewal and somatic cell reprogramming is discussed. (tocris.com)
  • This reporter cell line is useful for monitoring the activity of IFNγ-induced GAS signal transduction pathways. (atcc.org)
Proteins4
Receptor Tyrosin1
  • The Eph receptor tyrosine kinases and their membrane-bound ephrin ligands control a diverse array of cell-cell interactions in the developing and adult organisms. (rcsb.org)
Kinase2
  • PQQ augmented the expression of type I interferon receptor (IFNAR) and enhanced the IFN-β-mediated janus kinase (JAK1) and signal transducer and activator of transcription (STAT1) expression. (nih.gov)
  • BRAF is a protein kinase and part of the MAP kinase signalling cascade which involves transduction of a growth signal from the cell membrane to the nucleus via a chain of protein kinases and is responsible for cellular proliferation and survival. (hindawi.com)
Cascades2
  • Activated G alpha (s) and the beta:gamma dimer then participate in separate signaling cascades. (reactome.org)
  • Growth factors initiate numerous different signaling cascades in order to regulate cell differentiation and proliferation. (tocris.com)
Intracellular1
  • Despite the requirement for a number of transcription factors and secreted signalling molecules in sex determination, intracellular signalling components functioning in this process have not been defined. (plos.org)
Interaction1
  • Although cellular and in vivo studies have provided considerable insight into the downstream consequences of Notch signalling, relatively little is known about the molecular basis of the receptor/ligand interaction and initial stages of activation. (nih.gov)
Transcriptional2
  • therefore, we have analyzed domains and individual amino acids in the cytoplasmic region of the rat GHR required for ligand-mediated receptor internalization, receptor down-regulation, and transcriptional signaling. (ku.dk)
  • These results demonstrate that phenylalanine 346 is essential for GHR internalization and down-regulation but not for transcriptional signaling, suggesting that ligand-mediated endocytosis is not a prerequisite for GH-induced gene transcription. (ku.dk)
Protein5
  • The classical view of G-protein signalling is that the G-protein alpha subunit dissociates from the beta:gamma dimer. (reactome.org)
  • The ligands can have a glycosylphosphatidylinositol anchor (A type) or a membrane-spanning protein domain (B type). (hindawi.com)
  • We probe the open conformation of human Hsp90α for druggable sites that overlap with these allosteric control elements, and identify three putative natural compound allosteric modulators: Cephalostatin 17, 20(29)-Lupene-3β-isoferulate and 3′-Bromorubrolide F. We assess the allosteric potential of these ligands by examining their effect on the conformational dynamics of the protein. (nature.com)
  • These findings serve as an instructive example of the diversity of transmembrane domain formation within the same family of protein kinases and seem to favor the assumption that the so-called rotation-coupled activation mechanism may take place during the Eph receptor signaling. (rcsb.org)
  • Mathematical modeling of signal transduction networks has previously been used to map out thermodynamical using rate equations is increasingly attracting attention as a properties of protein-folding models (6,7). (lu.se)
Molecules3
  • Here, we systematically profiled the signaling responses to a panel of wild type and mutein IL-2 molecules in various Fc fusion configurations. (biorxiv.org)
  • The Wnt family encodes a large group of signaling molecules that are involved in cell proliferation, differentiation, migration and apoptosis [ 13 , 14 ]. (oncotarget.com)
  • MW) chemicals interact with host cells and molecules and In our daily life, we are confronted with a plethora of natural influence biologic processes such as signal transduction. (cdc.gov)
Downstream1
  • Our data indicate, for the first time, a requirement for MAPK signaling in the developing XY gonad in order to facilitate normal expression of SRY and the downstream testis-determining genes and also suggest that reduced dosage of MAP3K4 may be the cause of a previously described autosomal sex-reversing mutation in the mouse. (plos.org)
Differentiation1
  • Here we present SR1001, a high-affinity synthetic ligand-the first in a new class of compound-that is specific to both RORα and RORγt and which inhibits T H 17 cell differentiation and function. (nature.com)
MAPK2
  • An activating hotspot mutation occurs at V600E and results in constitutive MAPK signalling and uncontrolled cellular growth. (hindawi.com)
  • Moreover, we describe experiments showing the presence of activated MKK4, a direct target of MAP3K4, and activated p38 in the coelomic region of the XY gonad at 11.5 d post coitum, establishing a link between MAPK signalling in proliferating gonadal somatic cells and regulation of Sry expression. (plos.org)
Mechanism5
  • We find evidence for the selective allosteric activation and inhibition of Hsp90's conformational transition toward the closed state in response to ligand binding and shed valuable insight to further the understanding of allosteric drug design and Hsp90's complex allosteric mechanism of action. (nature.com)
  • A prominent phenotypic outcome of γ c receptor signaling is lymphoproliferation, and so the cytokines are often observed to be an endogenous or exogenous mechanism for altering the balance of immune cell types. (biorxiv.org)
  • The present study explores the possible involvement of a purinergic mechanism in mechanosensory transduction in the bladder using P2X 3 receptor knock-out (P2X 3 − /− ) and wild-type control (P2X 3 +/+ ) mice. (jneurosci.org)
  • However, the underlying signal transduction mechanism for these afferents is poorly understood. (jneurosci.org)
  • This analysis discriminates between different biological mechanisms to achieve a transient signal from a sustained TGF-b input, where one mechanism is to use a negative feedback to turn the signal off. (lu.se)
Dimeric2
  • Therapeutic ligands are often made dimeric as antibody Fc fusions to confer desirable pharmacokinetic benefits, with under-explored consequences on signaling. (biorxiv.org)
  • We found that dimeric muteins are uniquely specific for T reg s at intermediate ligand concentrations. (biorxiv.org)
Extracellular1
  • Recent advances in structure determination of the extracellular regions of human Notch-1 and one of its ligands Jagged-1 have given new insights into docking events occurring at the cell surface which may facilitate the development of new highly specific therapies. (nih.gov)
Effector1
  • Immunoreceptor signaling during development, homeostasis, and effector function of T cells and NK cells. (upstate.edu)
Concentrations2
  • We used a tensor-structured dimensionality reduction scheme to decompose the responses of each cell population to each ligand over a range of time points and cytokine concentrations. (biorxiv.org)
  • The mechanisms regulating follicle growth and development are under the control of changing concentrations of ligands ( i.e. hormones and growth factors). (glowm.com)
Cellular2
  • This enables cells to communicate and respond to external environments, maintain cellular homeostasis, and transduce signals. (mdpi.com)
  • These data demonstrate that MAP3K4-dependent signalling events are required for normal expression of Sry during testis development, and create a novel entry point into the molecular and cellular mechanisms underlying sex determination in mice and disorders of sexual development in humans. (plos.org)
Kinetics2
  • This altered selectivity is explained by altered surface receptor-ligand binding kinetics and can be quantitatively predicted using a multivalent binding model. (biorxiv.org)
  • It is used to simulate the Monte Carlo method, ST naturally provides ensembles of kinetics of large signaling networks, where one cannot only solutions rather than single ones, subject to analysis by rely on biological intuition. (lu.se)
Encodes2
  • The gene IFNGR1 encodes IFN-γR1, which is the ligand-binding chain (alpha) of the heterodimeric gamma interferon receptor, which is found on macrophages . (wikidoc.org)
  • IFNGR2 , encodes IFN-γR2, the non-ligand-binding partner of the heterodimeric receptor. (wikidoc.org)
Vivo1
  • The Optic Nerve Crush model provides an effective tool for analyzing the pathogenic mechanisms associated with neuronal injury signaling in vivo . (pharmoptima.com)
RTKs1
  • However, mutant RTKs may continue to send proliferative signals even in the absence of growth factor stimulation. (tocris.com)
Homeostasis1
  • The importance of these cytokines to immune homeostasis and challenges in altering their signaling toward specific therapeutic goals have inspired a variety of engineered forms. (biorxiv.org)
Occurs2
  • Eph/ephrin signal transduction occurs not only in the receptor-expressing cell but also in the ligand-expressing cell via bidirectional signaling [ 5 ]. (hindawi.com)
  • The binding of both NO and CO occurs via an axial ligand exchange process, and is fully reversible. (rcsb.org)
Involves1
  • Optical absorption, electron paramagnetic resonance and NMR spectroscopy have revealed that the heme groups of both sensor domains are high-spin and low-spin in the oxidized and reduced forms, respectively, and that the spin-state interconversion involves a heme axial ligand replacement. (rcsb.org)
Biological1
  • As described previously, studies into cold-sensitive fibers were elusive in defining the biological basis for cold signaling. (nih.gov)
Notch1
  • Mutations in the DSL (Delta, Serrate, Lag2) Notch (N) ligand Delta-like (Dll) 3 cause skeletal abnormalities in spondylocostal dysostosis, which is consistent with a critical role for N signaling during somitogenesis. (rupress.org)
Sensory1
  • However, in the mid- to late 1990s, a number of laboratories interested in cold transduction began to use primary cultures of either dorsal root (DRG) or trigeminal (TG) ganglia neurons as in vitro models of sensory afferents. (nih.gov)
Cancer1
  • In the current study, we examined the effects of recombinant ERRP on the growth and ligand-induced activation of multiple members of erbB family in three pancreatic cancer cell lines that express varying levels of EGFR and other member(s) of its family, specifically HER-2. (aacrjournals.org)
Molecular1
  • This chapter focuses on TRPM8, describing what was known about cold signaling before the channel was cloned, how TRPM8 was identified as a cold sensor, and what advances have been made in our understanding of the molecular logic for cold sensation since its identification. (nih.gov)
Reveals1
  • Further analysis in terms of parameter sensitivity reveals that this negative feedback loop in TGF-b signaling renders the system global robustness. (lu.se)
Immune2
  • In total, these findings represent a comprehensive analysis of how ligand properties, and their consequent effects on surface receptor-ligand interactions, translate to selective activation of immune cell populations. (biorxiv.org)
  • Significance Statement Signaling in off-target immune cells has hindered the effectiveness of IL-2 as an immunotherapeutic. (biorxiv.org)
Relation1
  • A possible role of membrane lipid rafts in relation to Eph transmembrane domain oligomerization and Eph signal transduction was also discussed. (rcsb.org)
Role1
  • CD3, also known as T3, is a member of the immunoglobulin superfamily that plays a role in antigen recognition, signal transduction, and T cell activation. (biolegend.com)
Growth1
  • Receptor-mediated endocytosis helps terminate the growth factor signal by internalizing the ligand-receptor complex. (tocris.com)
Cells3
  • Addition of FK1012 to the cells caused signal transduction. (wikipedia.org)
  • The effect of pyrroloquinoline quinine (PQQ) on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation was examined using RAW 264.7 macrophage-like cells. (nih.gov)
  • Excellent signal/background ratio and stable luciferase expression make this cell line ideal for in vitro study of CD19 specific CAR-T cells. (atcc.org)
Data1
  • We review the structural data available for receptor and ligands and identify the challenges ahead. (nih.gov)