• As mGluR1/5 signal transduction is complex and involves multiple partners, a better understanding of alterations in mGluR signalling in brain disorders will be required in order to discern the molecular and cellular basis of these pathologies. (nih.gov)
  • Signal transduction pathways stimulated by secreted growth factors are tightly regulated at multiple levels between the cell surface and the nucleus. (crick.ac.uk)
  • Prenatal exposure to arsenic and cadmium impacts infectious disease-related genes within the glucocorticoid receptor signal transduction pathway. (cdc.gov)
  • This research aimed to identify key genes/signal transduction pathways that associate prenatal exposure to these toxic metals with changes in infectious disease susceptibility using a Comparative Genomic Enrichment Method (CGEM). (cdc.gov)
  • A set of 82 infection and exposure-related genes was identified and found to be enriched for their role in the glucocorticoid receptor signal transduction pathway. (cdc.gov)
  • Given their common identification across numerous human cohorts and their known toxicological role in disease, the identified genes within the glucocorticoid signal transduction pathway may underlie altered infectious disease susceptibility associated with prenatal exposures to the toxic metals iAs and Cd in humans. (cdc.gov)
  • 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)
  • Signaling peptide receptor is a type of receptor which binds one or more signaling peptides or signaling proteins. (wikipedia.org)
  • Moreover, Group I mGluRs interact with a variety of different proteins that are important for the regulation of synaptic signalling, such as Homer and PDZ domain containing proteins, such as Tamalin. (nih.gov)
  • Fig. 1: Photochemistry of light-oxygen-voltage receptors and sequences of proteins under study. (nature.com)
  • The activity of these hormones is mediated by proteins belonging to the nuclear receptor superfamily. (igbmc.fr)
  • The growth/survival signal is initially carried by these receptor ligands - proteins such as epidermal growth factor (EGF), fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) - which bind cell-surface receptor tyrosine kinases (RTKs). (tocris.com)
  • Additionally, transforming growth factor β signals through receptor serine/threonine kinases (RSTKs) and activates downstream SMAD proteins to regulate the expression of specific genes. (tocris.com)
  • Deregulation of growth factor receptor activity is found in nearly all epithelial tumors, and the expression of mutant forms of growth factor proteins may also lead to cancer . (tocris.com)
  • Microdomains or lipid rafts greatly affect the distribution of proteins and peptides in the membrane and play a vital role in the formation and activation of receptor/protein complexes. (frontiersin.org)
  • Our simulation experiments indicate, that for receptor/raft ratios smaller than 1, i.e., when the number of raft compartments clearly exceeds the number of pathway specific membrane proteins, we observe significant decrease in LRP6 phosphorylation and downstream pathway activity. (frontiersin.org)
  • 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)
  • Tir acts as a cell-surface receptor in host cells, rewiring intracellular processes to assist infection by targeting multiple host proteins. (biorxiv.org)
  • This product category contains extracellular proteins of human, murine or rat sequence that, for the most part, initiate or otherwise affect signaling through cell surface receptors. (peprotech.com)
  • Productive interaction between receptors and G proteins involves multiple intracellular receptor domains, but the role of individual receptor amino acids in directing the selection of specific signaling pathways has not yet been identified. (aspetjournals.org)
  • To examine the role of this conserved threonine residue in 5-HT 1A receptor coupling to G i /G o proteins, this residue was mutated to alanine (T149A mutant). (aspetjournals.org)
  • THE nuclear receptor superfamily includes receptors for steroids, retinoids, thyroid hormone and vitamin D, as well as many related proteins. (northwestern.edu)
  • The activity of about two-thirds of the 48 nuclear receptors is controlled by selective ligands (e.g. steroid hormones, retinoids, intracellular lipids), and is fine-tuned by transcriptional coregulators forming macromolecular complexes that activate (coactivators) or repress (corepressors) the expression of target genes by modulating the accessibility of the transcriptional machinery to DNA. (igbmc.fr)
  • 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)
  • For receptors recognizing ligands of the transforming growth factor β (TGF-β) family, little is known about how trafficking is regulated or how this shapes signaling dynamics. (crick.ac.uk)
  • Pyk2 uncouples metabotropic glutamate receptor G protein signaling but" by Alexander A. Nicodemo, Macarena Pampillo et al. (uwo.ca)
  • Pyk2 uncouples metabotropic glutamate receptor G protein signaling but facilitates ERK1/2 activation. (uwo.ca)
  • Activation of ERβ by WAY-200070 also resulted in the phosphorylation of p21-activated kinase (PAK) and extracellular signal-regulated kinase 1/2 (ERK1/2) in cultured cortical neurons, suggesting a mechanism for the regulation of the actin cytoskeleton. (jneurosci.org)
  • Several signaling molecules have been identified as critical players in the regulation of insulin-induced IR activation. (mdpi.com)
  • Key signaling pathways are highlighted, and the regulation of ES cell self-renewal and somatic cell reprogramming is discussed. (tocris.com)
  • All compounds exhibited a similar requirement for receptor internalization to increase cAMP and proportion of FSHR endosomes with active Gαs, suggesting regulation of cAMP signaling induced by T1 may be altered. (frontiersin.org)
  • The goal of this minireview is to provide an update on the regulation of bile acid (BA) homeostasis by the nuclear receptor Farnesoid X receptor (FXR) and the effects on this regulation by exposure to environmental or therapeutic agents. (aspetjournals.org)
  • Membrane trafficking of G protein-coupled receptors (GPCRs) tightly orchestrates the signaling from this superfamily of signaling receptors. (frontiersin.org)
  • Estrogen receptor β (ERβ) is expressed in cortical neurons, and ERβ knock-out mice display impaired performance in cortically mediated processes, suggesting that signaling via this receptor has profound effects on cortical neuron function. (jneurosci.org)
  • However, the effect of rapid signaling through estrogen receptor β (ERβ) in cortical neurons is not known. (jneurosci.org)
  • Follicle-stimulating hormone receptor (FSHR) is a G protein-coupled receptor (GPCR) with pivotal roles in reproduction. (frontiersin.org)
  • The endocannabinoid system regulates appetite and energy expenditure and inhibitors of cannabinoid receptor 1 (CB-1) induce weight loss with improvement in components of the metabolic syndrome. (jci.org)
  • WNT signaling regulates central developmental processes of the cell, including cell fate, cell proliferation, cell migration and adult homeostasis. (frontiersin.org)
  • Leptin receptor signaling in midbrain dopamine neurons regulates feeding. (bvsalud.org)
  • The discovery provides new insight into the functioning of a common cell receptor called a G protein-coupled receptor or GPCR . (stanford.edu)
  • 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)
  • The expression levels of Gα subunits influence the biased profiling of β-agonists and antagonists in that they determine both their activity and efficacy by affecting different membrane distribution of receptor-G protein populations. (mdpi.com)
  • In the naïve state, the level of Gα expression influences the partitioning of not only Gα but also the co-expressed receptor in different membrane domains. (mdpi.com)
  • One key mechanism dictating the signal activity of GPCRs is membrane trafficking. (frontiersin.org)
  • Extrapolating/Translating these values to the membrane of a "normal sized" cell yields a raft abundance, that, by far, outnumbers the membrane-associated pathway components of most individual signaling pathway, such as receptor and kinases. (frontiersin.org)
  • Even though LRP6 is homogenously distributed in the membrane and only a minor fraction is raft-associated, its localization to lipid rafts is vital for the activation of the LRP6 signalosome, hence wnt/β-catenin signaling. (frontiersin.org)
  • For most individual signaling pathway, this quantitative point of view would imply, that rafts clearly outnumber the membrane-associated pathway components, such as receptor and kinases. (frontiersin.org)
  • Collectively, our findings provide an updated picture of Tir's intracellular side, highlighting its ability to mimic host disordered membrane receptors' versatility as a molecular strategy for host evasion. (biorxiv.org)
  • Group I metabotropic glutamate receptors (mGluRs) are coupled via Galphaq/11 to the activation of phospholipase Cbeta, which hydrolyzes membrane phospholipids to form inositol 1,4,5 trisphosphate and diacylglycerol. (uwo.ca)
  • Previous in vivo studies indicated that unlike the E. coli signal recognition particle (SRP), the SRP receptor FtsY is required for membrane targeting of ribosomes. (rupress.org)
  • Our results with E. coli , in conjunction with recent observations made with the yeast Saccharomyces cerevisiae , raise the possibility that the SRP receptor-mediated formation of intracellular membrane networks is governed by evolutionarily conserved principles. (rupress.org)
  • Nuclear receptors are transcription factors that transduce hormone signaling into a transcriptional response. (igbmc.fr)
  • 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)
  • Signaling via ERβ also resulted in activation of a PAK/ERK1/2 (extracellular signal-regulated kinase 1/2) signaling pathway. (jneurosci.org)
  • In separate rats, we measured the effects of salvA on activation of extracellular signal regulated kinase (ERK), cyclic adenosine monophosphate (cAMP) response element binding protein, and c-Fos within the NAc. (erowid.org)
  • The integration of GPCR and receptor tyrosine kinase (RTK) signaling, including IR upon ligand stimulation, is eloquently reviewed. (mdpi.com)
  • Receptor-mediated endocytosis helps terminate the growth factor signal by internalizing the ligand-receptor complex. (tocris.com)
  • Analysis of phosphorylation-dependent interactions downstream of VEGFR-1 in mammalian cells, which is generally hindered by the lack of ligand-induced receptor phosphorylation, was enabled by the development of chimeric receptors. (figshare.com)
  • The chimeric receptors were significantly activated in response to ligand, thereby enabling studies of this signalling with the putative effectors PKB/Akt, PLC and ERK1.2. (figshare.com)
  • Repeated exposure to drugs of abuse and stress increase dynorphin, a kappa opioid receptor (KOR) ligand, in the nucleus accumbens (NAc). (erowid.org)
  • Downregulation of ESCRT components increases the outputs of TGF-β signaling and sensitizes cells to low doses of ligand in their microenvironment. (crick.ac.uk)
  • Gint4.T aptamer is able to specifically bind to the human PDGFRβ ectodomain (Kd: 9.6 nmol/l) causing a strong inhibition of ligand-dependent receptor activation and of downstream signaling in cell lines and primary cultures of human glioblastoma cells. (unina.it)
  • Stimulation of Group I metabotropic glutamate receptors (mGluR1 and mGluR5) leads to activation of a wide variety of signalling pathways. (nih.gov)
  • We show here, that the proline-rich tyrosine kinase 2 (Pyk2) interacts with both mGluR1 and mGluR5 and is precipitated with both receptors from rat brain. (uwo.ca)
  • Any process that activates or increases the frequency, rate or extent of the activity of any intracellular steroid hormone receptor signaling pathway. (mcw.edu)
  • However, the signaling pathways downstream of p75 NTR that control growth cone functions, such as filopodial behavior, remain undefined. (jneurosci.org)
  • An upregulation of IR expression and its activation is significantly associated with higher downstream G protein signaling cascades. (mdpi.com)
  • Growth factors initiate numerous different signaling cascades in order to regulate cell differentiation and proliferation. (tocris.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)
  • Here, we produced mice that lacked CB-1 in hepatocytes or stellate cells to determine if CB-1 signaling contributes to the development of NAFLD or liver fibrosis. (jci.org)
  • In this study, we showed that receptor-type PTPϵ (PTPϵM) dephosphorylated IR in rat primary hepatocytes and tyrosines 972, 1158, 1162 and 1163 were primary targets of PTPϵM. (bioone.org)
  • In addition, Gint4.T aptamer prevents PDGFRβ heterodimerization with and resultant transactivation of epidermal growth factor receptor. (unina.it)
  • As a result, the combination of Gint4.T and an epidermal growth factor receptor-targeted aptamer is better at slowing tumor growth than either single aptamer alone. (unina.it)
  • Persistent signaling from the oncogenic epidermal development element receptor (EGFR) is certainly a major way to obtain cancers resistance to EGFR targeting. (bioinf.org)
  • Moreover, due to their effects on metabolism, proliferation and inflammation, their receptors are therapeutic targets for pathologies refractory to current treatments such as various autoimmune and rare diseases, as well as cancers. (igbmc.fr)
  • The aryl hydrocarbon receptor (AHR) is regarded as an important homeostatic transcriptional regulator within physiological and pathophysiological processes, including xenobiotic metabolism, endocrine function, immunity, and cancer. (aspetjournals.org)
  • In particular, drugs targeting receptor tyrosine kinases (RTKs) have been successful. (europa.eu)
  • Impaired insulin receptor (IR) signaling leads to insulin resistance and type 2 diabetes mellitus. (bioone.org)
  • A prominent example for the decisive impact of lipid rafts on signaling is LRP6, whose localization to the same lipid rafts domain as the kinase CK1γ is crucial for its successful phosphorylation and the subsequent activation of the signalosome, hence WNT/β-catenin signaling. (frontiersin.org)
  • To analyze whether and how the quantitative ratio between receptor and rafts affects LRP6 phosphorylation and WNT/β-catenin pathway activation, we present a computational modeling study, that for the first time employs realistic raft numbers in a compartment-based pathway model. (frontiersin.org)
  • Here, we apply computational modeling to analyze whether and how the quantitative ratio between receptor and rafts affects LRP6 phosphorylation and WNT/β-catenin pathway activation. (frontiersin.org)
  • Sequence alignment of several G protein-coupled receptors identified a highly conserved threonine residue in the i2 loop of the 5-hydroxytryptamine 1A (5-HT 1A ) receptor that is a putative protein kinase C phosphorylation consensus site and is located in a predicted amphipathic α-helical domain. (aspetjournals.org)
  • FXR, and possibly other nuclear receptors, may promote homeostasis not only by regulating expression of appropriate metabolic target genes but also by driving homeotrophic liver growth. (nih.gov)
  • However, the effects of ERβ-mediated signaling on dendritic spines of cortical neurons and the underlying molecular mechanisms are unknown. (jneurosci.org)
  • The goal of this proposal is to investigate the molecular mechanisms whereby RTK signalling output is modified, and how they are altered during cancer progression to metastatic disease. (europa.eu)
  • As T1-induced internalization was only marginally greater, the dramatic increase in recycling and cAMP signaling may be due to additional mechanisms. (frontiersin.org)
  • Although the signalling pathways induced by VEGF have been well-studied, the precise molecular mechanisms remain to be determined, particularly with respect to the relative contribution of the individual receptors. (figshare.com)
  • however, its functional relevance and signaling mechanisms are unclear. (gla.ac.uk)
  • 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)
  • Thus our findings unveil a novel molecular mechanism by which NRP1 can control EGFR signaling and tumor growth. (gla.ac.uk)
  • Targeting purinergic receptors to attenuate inflammation of dry eye. (bvsalud.org)
  • Purinergic Signal;2022 Feb 26. (bvsalud.org)
  • These suggested that purinergic receptors would be promising targets to control the inflammation of DED in the future . (bvsalud.org)
  • Multiple agonists of G-protein coupled receptors (GPCRs), beta-adrenergic receptors (β-ARs) in particular, scored in this screen. (biorxiv.org)
  • Furthermore, our findings propose a novel mechanism of action for β-AR agonists, shown beneficial in Parkinson's disease (PD), and suggests β-AR signaling as a potential druggable target for multiple conditions associated with ER-Mito contact dysregulation. (biorxiv.org)
  • Another example is the μ-opioid receptor (MOR), which is bound and activated by the opioid peptide hormone β-endorphin. (wikipedia.org)
  • An example is the tropomyosin receptor kinase B (TrkB), which is bound and activated by the neurotrophic protein brain-derived neurotrophic factor (BDNF). (wikipedia.org)
  • In mature bone, NGF is produced by osteoblasts following mechanical loading and signals through resident sensory nerves expressing its high affinity receptor, neurotrophic tyrosine kinase receptor type 1 (TrkA), to support bone formation. (jefferson.edu)
  • However, mutant RTKs may continue to send proliferative signals even in the absence of growth factor stimulation. (tocris.com)
  • Increased prevalence of spinal GluA2-lacking AMPARs in neuropathic pain is mediated by NMDA receptors and subsequent stimulation of calpain and calcineurin signaling. (aspetjournals.org)
  • We found that the extracellular domain of NRP1 interacts with the EGF receptor (EGFR) and promotes its signaling cascade elicited upon EGF or TGF-α stimulation. (gla.ac.uk)
  • While CB-1 blockage in brain is responsible for weight loss, many of the metabolic benefits associated with CB-1 blockade have been attributed to inhibition of CB-1 signaling in the periphery. (jci.org)
  • Inhibition of TLR4 signaling reduced Ngf expression in primary osteoblasts and RNA sequencing of bones from Tlr4 conditional knockout mice and wild-type littermates revealed dysregulated inflammatory signaling three days after osteogenic mechanical loading. (jefferson.edu)
  • We here report two patients with unusual mycobacterial infections, both diagnosed with homozygous deleterious interferon-γ receptor 1 gene mutations. (eur.nl)
  • Here we provide in vitro and in vivo evidence that identifies the CREB-binding protein (CBP) and its homologue P300 (refs 6, 7) as cofactors mediating nuclear-receptor-activated gene transcription. (northwestern.edu)
  • However, the effect of rapid signaling via ERβ on dendritic spines and the signaling pathways initiated by this receptor in cortical neurons are unknown. (jneurosci.org)
  • These data suggest that signaling through ERβ results in rapid modification of dendritic spines of cortical neurons, supporting the role of brain-synthesized estrogen as a postsynaptic morphogen. (jneurosci.org)
  • Blocking NMDA receptors abolished inward rectification of AMPAR-EPSCs of dorsal horn neurons in nerve-injured rats. (aspetjournals.org)
  • The hormone-receptor pair functions as a highly selective lock-and-key system that modulates the expression of many genes and the activities of target cells. (igbmc.fr)
  • As cAMP signaling drives gonadotrophin hormone receptor recycling, rapid exocytic events were evaluated at single event resolution. (frontiersin.org)
  • 2B receptor interference in type II alveolar epithelial cells, endothelial cells and M2 macrophages. (lu.se)
  • Our data reveal that Pyk2 couples the activation mGluRs to the mitogen-activated protein kinase pathway even though it attenuates mGluR1-dependent G protein signaling. (uwo.ca)
  • Likely via a radical-pair mechanism 12 , T 1 reacts within microseconds to the signaling state, characterized by a covalent thioadduct between a highly conserved cysteine residue in the LOV photosensor and the C4a atom of the flavin isoalloxazine ring system. (nature.com)
  • In addition, the observed dependence of some of these effects on a specific tyrosine residue within VEGFR-2 suggested that the chimeric receptors couple to downstream effectors in a manner analogous to that of the full-length receptors. (figshare.com)
  • 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)
  • To identify novel effectors downstream of these receptors, their intracellular domains were used as bait to screen yeast two-hybrid cDNA libraries. (figshare.com)
  • This paper provides a coherent picture of the intracellular side of Tir, highlighting its ability to copycat the interactions of disordered intracellular domains of host immune receptors. (biorxiv.org)
  • Dopamine D2-receptor blockade enhances decoding of prefrontal signals in humans. (cam.ac.uk)
  • Dopamine has long been suggested to play a key role in the integrity of such representations, with D2-receptor activation rendering them flexible but weak. (cam.ac.uk)
  • In the current study, we use dopamine receptor-specific pharmacology and multivoxel pattern-based functional magnetic resonance imaging to test the hypothesis that blocking D2-receptor activation enhances prefrontal representations. (cam.ac.uk)
  • These results suggest that D2-receptor blockade enhances content-specific representations in frontal cortex, presumably by a dopamine-mediated increase in pattern separation. (cam.ac.uk)
  • G protein-coupled receptors (GPCR) have recently been implicated in intracellular crosstalk pathways with IR. (mdpi.com)
  • Specifically, the researchers were able to illuminate the structure of the GPCR bonded with a signaling protein called arrestin . (stanford.edu)
  • In turn, receptor signaling is known to drive or regulate GPCR trafficking. (frontiersin.org)
  • Neurotrophins bind two classes of receptors, the receptor tyrosine kinase family of Trk (A, B, and C) receptors and the p75 neurotrophin receptor (NTR). (jneurosci.org)
  • Platelet-derived growth factor receptor β (PDGFRβ), a cell-surface tyrosine kinase receptor, is an important hallmark involved in glioma since it influences several cellular processes of tumor biology including proliferation, migration, and angiogenesis. (unina.it)
  • Specifically, the proposed research will significantly expand the understanding of the intersection between two interlinked networks that regulate RTK signalling, i.e. (europa.eu)
  • Our results suggest that pathway specific targeting and sorting mechanism are required to significantly narrow down the receptor/raft ratio and to enable the formation of the LRP6 signalosome, hence signaling. (frontiersin.org)
  • Although Tlr4 conditional knockout mice have normal skeletal mass and strength in adulthood, the loss of TLR4 signaling significantly reduced lamellar bone formation following loading. (jefferson.edu)
  • The glutamate AMPA receptors (AMPARs) are critically involved in the excitatory synaptic transmission, and blocking AMPARs at the spinal level reverses neuropathic pain. (aspetjournals.org)
  • Two main VEGF receptors are expressed in endothelial cells: VEGFR-1 and VEGFR-2. (figshare.com)
  • To address this inconsistency, this study investigated GPR18 coupling in a native neuronal system with endogenous signaling pathways and effectors. (unboundmedicine.com)
  • Moreover, consistent with the cortical distribution of D2 receptors, post hoc analyses showed enhanced decoding of motor signals in motor cortex, but not of visual signals in visual cortex. (cam.ac.uk)
  • G protein stoichiometry can dictate biased agonism through distinct receptor-G protein partitioning. (mdpi.com)
  • The VEE is a heterogeneous compartment containing the Adaptor Protein Phosphotyrosine Interacting with Pleckstrin homology Domain and Leucine Zipper 1 (APPL1) with distinct functions in regulating endosomal Gαs/cAMP signaling and rapid recycling. (frontiersin.org)
  • The temporal effects of salvA on ERK signaling suggest KOR-mediated engagement of distinct signaling pathways within the NAc that might contribute to biphasic effects on reward sensitivity. (erowid.org)
  • 2B receptor is located in typical pathological structures e.g. honeycomb cysts and weakly in fibroblast foci. (lu.se)
  • 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)
  • Here, we investigated whether osteoblastic expression of Toll-like receptor 4 (TLR4), a key receptor in the NF-κB signaling pathway, is required to initiate NGF-TrkA signaling required for load-induced bone formation. (jefferson.edu)
  • APPL1 plays a central role for GPCRs targeted to the VEE, and indeed, loss of APPL1 inhibited FSH-induced recycling and increased endosomal cAMP signaling. (frontiersin.org)
  • Critical physiological events throughout the body are controlled by extracellular signals from neurotransmitters and hormones acting on cell surface receptors. (duke.edu)
  • The role of CBP/P300 in the transcriptional response to cyclic AMP, phorbol esters, serum, the lipophilic hormones and as the target of the E1A oncoprotein suggests they may serve as integrators of extracellular and intracellular signalling pathways. (northwestern.edu)
  • Signaling without glutamine appears intrinsic to light-oxygen-voltage receptors, which pertains to biotechnological applications and suggests evolutionary descendance from redox-active flavoproteins. (nature.com)