• The purpose of this study was to prove the presence of NGF (nerve growth factor) and its receptor TrkA (tyrosine kinase receptor) with immunofluorescence. (sigmaaldrich.com)
  • Product Description google Tyrosine Kinase Receptor A (TrkA)-Fc Chimera, Purified Recombinant Protein, suitable to Block. (biosensis.com)
  • Scientific Background TrkA is a member of the neurotrophic tyrosine kinase receptor family. (biosensis.com)
  • p75NTR is an unusual member of this family due to its propensity to dimerize rather than trimerize, because of its ability to act as a tyrosine kinase co-receptor, and because the neurotrophins are structurally unrelated to the ligands, which typically bind TNFR family members. (wikipedia.org)
  • When p75NTR initiates apoptosis, NGF binding to Tropomyosin receptor kinase A (TrkA) can negate p75NTR apoptotic effects. (wikipedia.org)
  • TrkA (tropomyosin receptor kinase A) encodes a member of the neurotrophic tyrosine kinase receptor (NTKR) family. (thermofisher.com)
  • The biological activities of the neurotrophins are mediated by binding to the different members of the Trk family tyrosine kinase receptors. (rndsystems.com)
  • An orally bioavailable inhibitor of cyclin-dependent kinases (CDKs) and thropomyosin receptor kinase A (TRKA), with potential antineoplastic activity. (ncats.io)
  • CDK2/TRKA inhibitor PHA-848125 AC potently inhibits cyclin-dependent kinase 2 (CDK2) and exhibits activity against other CDKs including CDK1 and CDK4, in addition to TRKA. (ncats.io)
  • Dual targeting of CDK and tropomyosin receptor kinase families by the oral inhibitor PHA-848125, an agent with broad-spectrum antitumor efficacy. (ncats.io)
  • Gene mutations that cause loss of receptor function are associated with CONGENITAL INSENSITIVITY TO PAIN WITH ANHIDROSIS, while gene rearrangements that activate the protein-tyrosine kinase function are associated with tumorigenesis. (bvsalud.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)
  • Fusions involving the tropomyosin-related kinase (TRK) family of neurotrophin receptor tyrosine kinases have been identified in various human cancers and suggested to function as oncogenic drivers. (aacrjournals.org)
  • A 41-year-old woman who presented with undifferentiated soft-tissue sarcoma and lung metastases was found to harbor a gene fusion consisting of the 5′ region of lamin A/C ( LMNA ) and the 3′ region of neurotrophic tyrosine kinase receptor type 1 ( NTRK1 , encoding TRKA). (aacrjournals.org)
  • An Introduction and Overview of RON Receptor Tyrosine Kinase Signaling. (uc.edu)
  • The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) commonly targeted for inhibition by anti-cancer therapeutics. (biorxiv.org)
  • The epidermal growth factor receptor (EGFR) is a HER-family receptor tyrosine kinase (RTK) that is involved in cell signaling in healthy tissue. (biorxiv.org)
  • NTRK (neurotrophic tyrosine receptor kinase) gene fusions that encode chimeric proteins exhibiting constitutive activity of tropomyosin receptor kinases (TRK), are oncogenic drivers in multiple cancer types. (bvsalud.org)
  • The solvent-front (SF), gatekeeper, and xDFG motif mutations of tropomyosin receptor kinase (TRK) mediating acquired resistance of larotrectinib and entrectinib represent an unmet clinical need. (bvsalud.org)
  • For example, in vertebrate sympathetic neurons, target-derived NGF binds an axonal receptor tyrosine kinase, TrkA, to mediate constructive events, whereas the tumor necrosis factor receptor (TNFR) family member p75 NTR mediates destructive events. (rupress.org)
  • The p75 neurotrophin receptor (p75NTR) was first identified in 1973 as the low-affinity nerve growth factor receptor (LNGFR) before discovery that p75NTR bound other neurotrophins equally well as nerve growth factor. (wikipedia.org)
  • Degeneration of basal forebrain cholinergic neurons contributes significantly to the cognitive deficits associated with Alzheimer's disease (AD) and has been attributed to aberrant signaling through the neurotrophin receptor p75 (p75 NTR ). (plos.org)
  • Dr. Longo has financial interests in PharmatrophiX, a company focused on the development of neurotrophin receptor ligands. (plos.org)
  • BFCN atrophy involves aberrant signaling through the neurotrophin receptor p75 (p75 NTR ). (plos.org)
  • They chose the model helical dimer glycophorin A and the transmembrane region of the TrkA neurotrophin receptor, which have a similar structure but different amino acid sequences. (h-its.org)
  • This indicates a possible therapeutic area for the antibodies that could block the NGF/TrkA system, in order to modulate the frequency and the duration of the action potential of nociceptive neurons during chronic inflammation. (sigmaaldrich.com)
  • Neurotrophic factor receptors, including p75NTR, are responsible for ensuring a proper density to target ratio of developing neurons, refining broader maps in development into precise connections. (wikipedia.org)
  • Postnatal changes in the expression of the trkA high-affinity NGF receptor in primary sensory neurons. (ox.ac.uk)
  • We have tested this possibility by counting the number of L4/5 DRG neurons showing immunoreactivity for trkA in rats from the day of birth to postnatal day 14. (ox.ac.uk)
  • Because of these profound effects on ligand specificity, reverse transcription-PCR was used to understand the expression of the FL and ED receptor isoforms at the level of single neurons. (jneurosci.org)
  • Neurons are capable of expressing a surprising diversity of trk receptor structural isoforms that arise via alternative splicing ( Barbacid, 1994 ). (jneurosci.org)
  • 1 "We have utilized cells recombinantly overexpressing Trk-receptors, cell lines with endogenous expression, primary neurons, or in vivo studies to further addressed the mechanism by which triazinetriones increase the activity of Trk-receptors and downstream signaling," the authors wrote. (psychiatrictimes.com)
  • We find that NGF-QDs bind and activate TrkA surface receptors in PC12 neurons. (elsevierpure.com)
  • TrkA is required for high-affinity binding to nerve growth factor (NGF), neurotrophin-3 and neurotrophin-4/5 but not brain-derived neurotrophic factor (BDNF). (biosensis.com)
  • Cleavage of proforms into mature Neurotrophins allows the mature NGF and BDNF to activate TrkA-mediated survival mechanisms. (wikipedia.org)
  • Sortilin is required for many apoptosis-promoting p75NTR reactions, functioning as a co-receptor for the binding of neurotrophins such as BDNF. (wikipedia.org)
  • Brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) activated the FL receptor, as determined by tyrosine phosphorylation. (jneurosci.org)
  • As found for the ED isoform, the FL mutated receptor displayed a similar loss of NT-3- and NT-4-mediated activation, in addition to a diminished responsiveness to BDNF. (jneurosci.org)
  • Although NT-3, NT-4, and BDNF activate FL receptors, only BDNF is capable of robust but decreased activation of ED receptors. (jneurosci.org)
  • TrkA binds NGF, TrkB binds BDNF and NT-4/5 and TrkC binds NT-3. (rndsystems.com)
  • Using TrkA or TrkB receptor gene knockout HT-22 cells, the selectivity of the interaction of the low-molecular-weight dipeptide BDNF mimetic GSB-106 (hexamethylenediamide bis(N-monosuccinyl-L-seryl-L-lysine)) with TrkB receptors was shown. (bvsalud.org)
  • TrkA and nerve growth factor receptor (NGFR) are focused, two receptors that are activated by NGF, a neurotrophin expressed at high levels in OSCC. (nyu.edu)
  • Neurotrophic factor receptors bind Neurotrophins including Nerve growth factor, Neurotrophin-3, Brain-derived neurotrophic factor, and Neurotrophin-4. (wikipedia.org)
  • Two distinct subpopulations of Olfactory ensheathing glia have been identified with high or low cell surface expression of low-affinity nerve growth factor receptor (p75). (wikipedia.org)
  • In development approximately 70-80% of dorsal root ganglion (DRG) cells are dependent on nerve growth factor (NGF) for their survival, while in the adult only some 40% of DRG cells express the high-affinity NGF receptor, trkA. (ox.ac.uk)
  • These peripheral cold receptors, both Aδ- and C-fibers, have thermal thresholds (i.e., the temperature at which nerve impulses are generated) for cold activation between 30-20°C, temperatures considered to be innocuously cool [ 4 , 6 ]. (nih.gov)
  • We have studied the intracellular trafficking of TrkA receptors using QDs conjugated with nerve growth factor, a neuropeptide ligand critical for nervous system development and regulation. (elsevierpure.com)
  • Besides, NGF binding to TrkA receptors encouraged the intracellular Warburg effect in PC and DRG cells. (hindawi.com)
  • There is considerable evidence showing that the system constituted by the NGF and its high-affinity receptor TrkA plays a fundamental role in the molecular processes underlying the main forms of 'persistent' pain. (sigmaaldrich.com)
  • Alternative splicing of the avian trkB receptor generates an extracellular deletion (ED) isoform missing 11 amino acids from the neurotrophin-binding domain of the full-length (FL) receptor. (jneurosci.org)
  • The trk receptors, a family of receptor tyrosine kinases including trkA, trkB, and trkC, serve as the principal signal-transducing receptors for the neurotrophins ( Barbacid, 1994 ). (jneurosci.org)
  • In this study, comparison of the ligand specificity of the full-length (FL) and ED receptor isoforms revealed that ED trkB exhibits a more restricted neurotrophin specificity than does FL trkB. (jneurosci.org)
  • Receptor dimerization and autophosphorylation attracts proteins containing Src homology 2 (SH2) or phosphotyrosine binding (PTB) domains including adaptor proteins like FRS2 and GRB2. (springer.com)
  • There are 3 NTRK genes (1, 2, and 3) that contain the information for making three similar proteins: TRK-A, TRK-B, and TRK-C. The normal TRK proteins are receptors mostly found on the surface of cells of the nervous system. (ccalliance.org)
  • https://doi.org/10.1083/jcb.201607098 ) explore the evolutionary origins of these cues and report that in Drosophila melanogaster pro- and mature neurotrophins are capable of inducing death and survival pathways, respectively, by binding Toll receptor family members, which then recruit distinct sets of effector proteins. (rupress.org)
  • It is a membrane-bound receptor that upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. (biosensis.com)
  • To reveal that the NGF-TrkA signaling pathway was closely associated with PC PNI, in vitro neuroinvasion model was established by using MiaPaCa-2 cells via coculturing DRG cells in Matrigel. (hindawi.com)
  • TrkA is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. (thermofisher.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)
  • Lipocalin 10 is essential for protection against inflammation-triggered vascular leakage by activating LDL receptor-related protein 2-slingshot homologue 1 signalling pathway. (uc.edu)
  • transient receptor potential cation. (wikigenes.org)
  • MCs can secrete nociceptor sensitizing and activating agents, such as serotonin, prostaglandins, histamine, and proteolytic enzymes that can also activate the pain-mediating transient receptor potential vanilloid channels. (frontiersin.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)
  • Sequence A DNA sequence encoding the signal peptide and extracellular domain of human TrkA (amino acids 1- 413) was fused to the Fc region of human IgG1 (amino acids 104-330). (biosensis.com)
  • KLH conjugated synthetic phosphopeptide derived from human TrkA around the phosphorylation site of Tyr496. (thermofisher.com)
  • In recent years, the search for intracellular signaling integrator downstream of receptor tyrosine kinases provided valuable novel substrates. (springer.com)
  • This effect can be counteracted by anti-apoptotic signaling by TrkA. (wikipedia.org)
  • Neuronal responsiveness to the neurotrophins is determined not only by restricted expression and regulated release of the neurotrophins but also by the expression pattern of neurotrophin receptors and components of the signaling complex. (jneurosci.org)
  • Given the critical nature of receptor internalization and endosomal signaling for FSHR activity, we assessed whether these compounds exhibit differential abilities to alter receptor endosomal trafficking and signaling within the VEE. (frontiersin.org)
  • As cAMP signaling drives gonadotrophin hormone receptor recycling, rapid exocytic events were evaluated at single event resolution. (frontiersin.org)
  • 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)
  • Membrane trafficking of G protein-coupled receptors (GPCRs) tightly orchestrates the signaling from this superfamily of signaling receptors. (frontiersin.org)
  • In turn, receptor signaling is known to drive or regulate GPCR trafficking. (frontiersin.org)
  • Toll-like Receptor 4 Signaling in Osteoblasts Is Required for Load-Ind" by Ibtesam Rajpar, Gaurav Kumar et al. (jefferson.edu)
  • The molecular underpinnings common to and connecting these disorders are not known, but may include shared genetic risk factors ( 1 , 8 ), regulation of brain cations ( 9 , 10 ), or common receptor signaling events that activate pain ( 11 ), inflammation ( 12 ), or oxidative ( 13 ) pathways. (frontiersin.org)
  • Assisting this hypothesis, the selective TrkA agonist D3 rescued neurotrophin signaling in TgCRND8 mice, whereas NGF, getting together with both p75NTR and TrkA, didn't. (grandlacs-med-journal.com)
  • SUBCELLULAR LOCATION: TrkA is a heavily glycosylated transmembrane protein and contains 13 potential N-linked glycosylation sites. (biosensis.com)
  • Mutations in TrkA have been associated with congenital insensitivity to pain, anhidrosis, self-mutilating behavior, mental retardation and cancer. (thermofisher.com)
  • p75NTR is a neurotrophic factor receptor. (wikipedia.org)
  • p75NTR is a member of the tumor necrosis factor receptor superfamily. (wikipedia.org)
  • p75NTR/LNGFR was the first member of this large family of receptors to be characterized, that now contains about 25 receptors, including tumor necrosis factor 1 (TNFR1) and TNFR2, Fas, RANK, and CD40. (wikipedia.org)
  • proNGF and proBNDF interact with p75NTR and cause p75NTR-mediated apoptosis without activating TrkA-mediated survival mechanisms. (wikipedia.org)
  • We suggest that revitalizing the TrkA receptor, without p75NTR activation, can be key for restorative efficacy. (grandlacs-med-journal.com)
  • The time course and spatial localization of activated ligand-receptor complexes and their trafficking within cells is becoming increasingly understood as vital for propagating cell signals. (elsevierpure.com)
  • Follicle-stimulating hormone receptor (FSHR) is a G protein-coupled receptor (GPCR) with pivotal roles in reproduction. (frontiersin.org)
  • The receptors are ligand binding factors of type 1, 2 or 3 and protein-molecules that receive chemical-signals from outside a cell. (gentaur.com)
  • In this sense, am olfactory receptor is a protein-molecule that recognizes and responds to endogenous-chemical signals, chemokinesor cytokines e.g. an acetylcholine-receptor recognizes and responds to its endogenous-ligand, acetylcholine. (gentaur.com)
  • Estrogen Receptor Immunoreactivity in the Adult Primate Brain: Neuronal Distribution and Association with p75, trkA, and Choline Acetyltransferase. (bvsalud.org)
  • Screen drug effects on a specific receptor or full panels in agonist or antagonist mode. (indigobiosciences.com)
  • The complex splicing patterns of the trk receptors suggest alternative splicing as an important additional means of regulating neuronal responsiveness to the neurotrophins. (jneurosci.org)
  • TrkA leads to cell differentiations and may play a role in specifying sensory neuron subtypes. (biosensis.com)
  • When expressed in fibroblasts, the ED isoform exhibited restricted neurotrophin specificity compared with that of the FL receptor. (jneurosci.org)
  • It is demonstrated that targeted knockdown of these two receptors inhibits proliferation and invasion in an in vitro and preclinical model of OSCC, and metastasis, PNI, and pain. (nyu.edu)
  • It is further determined that TrkA knockdown alone inhibits thermal hyperalgesia, whereas NGFR knockdown alone inhibits mechanical allodynia. (nyu.edu)
  • The expression of p75 did not parallel that of trkA, remaining relatively constant at between 45 and 50% of cells from birth to postnatal day 14. (ox.ac.uk)
  • Consistent with this suggestion are the results of double labelling for trkA and IB4, which confirmed that at times intermediate between birth and postnatal day 14 there was a high degree of coexpression between these markers (which is absent in the adult). (ox.ac.uk)
  • On the day of birth, 71% of DRG cells were found to express trkA. (ox.ac.uk)
  • Since in the adult the IB4 population consists of small cells which mostly do not express trkA, this finding suggests that the postnatal down-regulation of trkA occurs in this population. (ox.ac.uk)
  • TrkA expression was knocked down in MiaPaCa-2 and dorsal root ganglion (DRG) cells treated with NGF to determine its effect on the Warburg effect. (hindawi.com)
  • These findings displayed that NGF/TrkA encouraged the neuroinvasive potential of PC cells by activating the Warburg effect in DRG cells through upregulation of TDE-miR-21-5p expression. (hindawi.com)
  • However, the movement and fate of ligand-receptor pairs inside cells is difficult to define with current technologies. (elsevierpure.com)
  • These results indicate that QDs can serve as effective high-resolution probe to track ligand-receptor function in the interior of cells. (elsevierpure.com)
  • is given by Pontus Forsell, Head of Discovery and Research at AlzeCure Pharma, and describes the research used to develop ACD856 in the NeuroRestore platform and the TrkA-NAM project in the Painless platform. (accesswire.com)
  • TrkA blocking-up could restrain NGF induced PC cell migration and neural invasion. (hindawi.com)
  • The use of PathHunter cell lines to discover modulators of Trk receptors. (accesswire.com)
  • When such chemical-signals couple or bind to a receptor, they cause some form of cellular/tissue-response, e.g. a change in the electrical-activity of a cell. (gentaur.com)
  • This discrepancy suggests that trkA expression, and therefore neurotrophin sensitivity, may alter as the animal matures. (ox.ac.uk)
  • We and others have used the PathHunter assay to demonstrate pharmacological effects on Trk-receptors. (psychiatrictimes.com)
  • Las mutaciones genéticas que causan pérdida de la función del receptor se asocian a insensibilidad congénita al dolor con anhidrosis, mientras que los reordenamientos genéticos que activan la función se asocian a oncogénesis. (bvsalud.org)
  • Among other things, it describes how the compounds were developed in AlzeCure's internal research, how they affect the target mechanism in cellular studies and how these effects manifest themselves in vivo, with potent positive cognitive effects with NeuroRestore and pain-relieving effects with TrkA-NAM. (accesswire.com)