• Direct regulation of T cell function by microbial ligands through Toll-like receptors (TLR) is an emerging part of T cell biology. (mingsheng88.org)
  • 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)
  • They are G protein-coupled receptors that are activated by synthesized ligands that wouldn't normally exist in the cell, such as the anti-psychotic Clozapine, allowing researchers to control the interaction externally and independent of internal activation. (wikipedia.org)
  • The ability to control this externally by spraying the PYR1MANDI (orthogonal receptor) with mandipropamid (orthogonal ligand and fungicide) has the potential to reduce crop yield loss during droughts in plants with these engineered receptors, and has been confirmed to work in canola. (wikipedia.org)
  • Designing ligands for mutant receptors that are unresponsive to the natural ligand could prove to be an effective way to treat disease. (wikipedia.org)
  • Hassan and Koh showed QH2 (orthogonal ligand) was able to allosterically activate the mutant TRβ nuclear hormone receptors that had lost their responsiveness to endogenous T3 (natural mutants) but retained their DNA binding activity. (wikipedia.org)
  • Mixing and matching the ligand-binding domains and DNA-binding domains of different hormone receptors can be used as an inducible expression mechanism to study the action of any gene with a hormone response element in its promoter. (wikipedia.org)
  • the development of imaging ligands for visualizing changes in receptors or other brain proteins relevant to substance abuse and co-occurring psychiatric disorders (e.g., anxiety, depression), 4. (nih.gov)
  • We analysed the mRNA expression levels of all known vascular endothelial growth factor (VEGF) ligands and receptors in human endometrium collected in the menstrual and proliferative phases of the menstrual cycle. (amsterdamumc.org)
  • Two periods of elevated mRNA expression of ligands and receptors were observed, separated by a distinct drop at cycle days (CDs) 9 and 10. (amsterdamumc.org)
  • Changes in VEGF ligands and receptors were associated with elevated expression of the hypoxia markers HIF1alpha and CA-IX in the menstrual and early proliferative phases. (amsterdamumc.org)
  • The gene product is a member of the nuclear hormone receptor family, a group of transcription factors regulated by small hydrophobic hormones, a subset of which do not have known ligands and are referred to as orphan nuclear receptors. (cancerindex.org)
  • The protein has been shown to interact with retinoid and thyroid hormone receptors, inhibiting their ligand-dependent transcriptional activation. (cancerindex.org)
  • ST3Gal1 and other sialyltransferases have been implicated in cancer immune suppression by synthesizing sialoglycans, which act as ligands for Siglec receptors. (york.ac.uk)
  • Ligand-induced stimulation of endogenous Notch receptors with Delta4 mimicked the activity of Notch1-IC toward EBF. (lu.se)
  • The total number of GPCRs is estimated to be around 800 where approximately 160 still are "orphans", meaning that the endogenous ligands are unknown. (lu.se)
  • CMKLR1/ChemR23 is a GPCR that was recently "de-orphanized" when the endogenous ligand, TIG2/chemerin, was isolated from inflammatory fluids and hemofiltrate. (lu.se)
  • Of utmost importance, we provide the first evidence that PD-1 ligand expression is regulated through proteolytic cleavage by endogenous matrix metalloproteinases (MMPs) without transcriptional alteration during culture-time. (crcm-marseille.fr)
  • In conclusion, differential regulation of endogenous 1 alpha 25(OH)(2)D(3) ligand and its nuclear receptor appear to be important regulators of DC biology and represent potential targets for the manipulation of DC function. (birmingham.ac.uk)
  • Functional regulation of CD22 by these endogenous ligands enhances BCR ligation -induced signaling and is essential for normal B cell responses to Ags. (bvsalud.org)
  • Our results suggest that CD22 but not CD45 is an endogenous ligand of CD22 that enhances BCR ligation -induced signaling through SHP-1-mediated dephosphorylation of CD22 in CD22 clusters. (bvsalud.org)
  • Those ligands can be endogenous, naturally occurring, and/or anthropogenic. (biolegend.com)
  • 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)
  • Following terminal differentiation induced by a diverse set of maturation stimuli, there is marked transcriptional up-regulation of 1 alpha OHase leading to increased 1 alpha OHase enzyme activity. (birmingham.ac.uk)
  • In order to test this hypothesis and identify novel components that are required for Mtb signaling and survival during infection, we propose to characterize the protein interaction partners of Rv3561 and small-molecule ligands, and further to define the transcriptional networks affected by Rv3561. (ssgcid.org)
  • In vitro studies and gene expression profiles showed that the transcriptional changes by the activated Ahr are ligand specific and are highly cell specific. (biolegend.com)
  • Ligand-activated transcriptional activator. (biolegend.com)
  • created an orthogonal receptor-ligand interface between PYR1 and mandipropamid. (wikipedia.org)
  • 2015. Assessing the Suitability of the Multilevel Strategy for the Conformational Analysis of Small Ligands . (ub.edu)
  • Orthogonal ligand-protein pairs (also known as re-engineered ligand-receptor interfaces or re-engineered enzyme-substrate interactions) are a protein-ligand binding pair made to be independent of the original binding pair. (wikipedia.org)
  • Furthermore, we study the functional consequences of protein-ligand interactions and the regulation of these interactions. (lu.se)
  • 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)
  • Different putative ligand structures have been identified for which the selectins show high affinity. (biovendor.com)
  • There is only one ligand binding pocket in the AHR (in the Per-ARNT-Sim-B domain), and the affinity of the best characterized high affinity ligand, TCDD (2,3,7,8-tetrachlorodibenzo-pdioxin), depends on only a few amino acids in that pocket. (biolegend.com)
  • Receptor for TNFSF13/APRIL and TNFSF13b/TAll1/BAFF/BLYS that binds both ligands with similar high affinity. (lu.se)
  • The synthetic chemist's approach is to take an already existing mutant form of the protein that binds the original ligand weakly, and synthesize a new ligand for which the mutant protein has a strong affinity. (wikipedia.org)
  • Both types of domains are commonly found in signaling proteins, particularly in prokaryotes, where they often function either as a sensor domain that directly recognizes ligands or as a protein-protein interaction domain (Heikaus et al . (ssgcid.org)
  • DNA microarray and Western blot analyses of key apoptosis-regulatory proteins in the transformed cells revealed FLICE-inhibitory protein (FLIP) as an important target of regulation by SWCNT. (cdc.gov)
  • I found that down-regulation of both these proteins is associated with poor prognosis for colon cancer patients. (lu.se)
  • The protein encoded by this gene is an unusual orphan receptor that contains a putative ligand-binding domain but lacks a conventional DNA-binding domain. (cancerindex.org)
  • Dual PD-1 ligand neutralization is required to abrogate (i) binding of the PD-1-Fc fusion protein, (ii) early apoptosis of T cells, and (iii) inhibition of T cell proliferation. (crcm-marseille.fr)
  • In contrast, carcinoma-associated fibroblasts appear PD-1 ligand-depleted through MMP activity that may impair physical deletion of exhausted defective memory T cells through apoptosis and facilitate their regulatory functions. (crcm-marseille.fr)
  • The antitumor effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in gliomas has thus far only been thoroughly established in tumor cell lines. (aacrjournals.org)
  • Due to the pleiotropic effect of bortezomibenhanced TRAIL DISC formation upon TRAIL triggering, down-regulation of cFLIP L and activation of the intrinsic apoptosis pathway seem to cooperatively contribute to the antitumor effect of bortezomib/TRAIL cotreatment. (aacrjournals.org)
  • Prenatal DES exposure caused thymic atrophy, apoptosis, and up-regulation of Fas and Fas ligand (FasL) expression in thymocytes. (aspetjournals.org)
  • As compared to passage-matched control cells, SWCNT-transformed BEAS-2B cells exhibited resistance to apoptosis induced by death ligands, e.g., tumor necrosis factor-a and Fas ligand, but not by inducers of mitochondria-mediated apoptosis, e.g., antimycin A and cisplatin, suggesting death receptor pathway as the primary pathway of defective apoptosis in SWCNT-transformed cells. (cdc.gov)
  • Overexpression of FLIP increased apoptosis resistance of the cells, whereas RNAi knockdown of FLIP reversed the apoptosis resistance of cells in response to death ligands. (cdc.gov)
  • However, disruption of ligand binding of CD22 enhances CD22 phosphorylation , a process required for CD22-mediated signal inhibition, upon BCR ligation in CD45-/- as well as wild-type mouse B cells but not in mouse B cells expressing a loss-of-function mutant of SHP-1. (bvsalud.org)
  • cAMP profoundly affects Mtb gene regulation and is required for virulence, and secretion of cAMP into the host disrupts the host's immune response to infection (Bai et al . (ssgcid.org)
  • 2020. Ligand dependent gene regulation by transient ERα clustered enhancers. . (ncbs.res.in)
  • Regulation and function of Zip4, the acrodermatitis enteropathica gene. (medscape.com)
  • Demonstration that the ATP-binding site spans both the N- and C-terminal halves of the protein explains the decreased affinity of gelsolin for this ligand in the presence of calcium ions, which induce separation of the halves as part of the activation process. (ubc.ca)
  • Low molecular weight (LMW) allosteric FSHR ligands were developed for use in assisted reproductive technology yet could also provide novel pharmacological tools to study FSHR. (frontiersin.org)
  • In this approach one has to be careful to only change the ligand specificity without changing the other actions of the protein. (wikipedia.org)
  • We used this module to create PYR1* MANDI /HAB1* and PYR1* AZIN /HAB1*, which possess nanomolar sensitivities to their activating ligands mandipropamid and azinphos-ethyl. (nature.com)
  • Imaging of biochemically recurrent prostate cancer has been established as a widely accepted clinical indication for PSMA ligand PET/CT in many parts of the world because of the results of multiple, primarily retrospective, studies that indicate superior detection efficacy compared with standard-of-care imaging. (snmjournals.org)
  • It is unclear how the synthesis of Siglec ligands is regulated, and little is known about the role of glyco-immune checkpoints in prostate cancer. (york.ac.uk)
  • The drawback of this approach is the protein still interacts weakly with the natural ligand at low synthetic ligand concentrations. (wikipedia.org)
  • CD22 recognizes α2,6 sialic acid as a specific ligand and interacts with α2,6 sialic acid -containing membrane molecules, such as CD45, IgM , and CD22, expressed on the same cell . (bvsalud.org)
  • We observed a significant up-regulation of 15-PGDH after treatment with LTC 4 , a CysLT 2 ligand, in colon cancer cells at both the mRNA and protein levels, which could be reduced by a CysLT 2 antagonist or a JNK inhibitor. (lu.se)
  • Bone resorption is dependent on a cytokine known as RANKL (receptor activator of nuclear factor κB ligand), a TNF family member that is essential for osteoclast formation, activity, and survival in normal and pathological states of bone remodeling. (elsevierpure.com)
  • Kearns, AE , Khosla, S & Kostenuik, PJ 2008, ' Receptor activator of nuclear factor κB ligand and osteoprotegerin regulation of bone remodeling in health and disease ', Endocrine reviews , vol. 29, no. 2, pp. 155-192. (elsevierpure.com)
  • Cells synthesize and release signalling molecules (ligands), which produce a specific response only in those cells that have a receptor for that ligand. (lu.se)
  • For example, there is currently no ligand available for non-invasive imaging of latent HIV in the human brain, which would be valuable for treatment of HIV/AIDS, or for detection of metabolites and signaling molecules associated with multiple glial cell types, which could shed light on the involvement of glial cell activity in substance use disorders (SUD). (nih.gov)
  • the development of imaging ligands for visualizing neuronal and/or glial retrograde/signaling molecules (e.g., glutamine, anandamide). (nih.gov)
  • Our new modules enable ligand-programmable multi-channel CID systems for plant and eukaryotic synthetic biology that can empower new plant-based and microbe-based sensing modalities. (nature.com)
  • Starting with the Escherichia coli lac operon in the 1970s, many synthetic ligand-regulated circuits have been built by rewiring natural systems for new functions 1 . (nature.com)
  • Due to a common structural element, the amino-terminal lectin-like domain, the selectins are able to bind to carbohydrate ligands. (biovendor.com)
  • The protein engineering approach involves synthesizing a new ligand and directed mutation of the protein's ligand-binding site. (wikipedia.org)
  • Furthermore, we also observed that LTC 4 , via the CysLT 2 /JNK signaling pathway, increased the expression of the differentiation markers sucrase-isomaltase and mucin-2 in colon cancer cells and that down-regulation of 15-PGDH totally abolished the observed increase in these markers. (lu.se)
  • To examine the mechanism underlying DES-mediated regulation of Fas and FasL, we performed luciferase assays using T cells transfected with luciferase reporter constructs containing full-length Fas or FasL promoters. (aspetjournals.org)
  • The Aryl hydrocarbon receptor (AHR) is a member of the basic helix-loop-helix-PER- ARNT-SIM (bHLH-PAS) subgroup of the bHLH superfamily of transcription factors and is the only member of this family known to be activated by ligands. (biolegend.com)
  • Receptor down-regulation in transiently transfected COS-7 cells was also dependent upon the phenylalanine 346 residue of the GHR, since no GH-induced down-regulation was observed in cells expressing the F346A GHR mutant. (ku.dk)
  • A novel regulation of PD-1 ligands on mesenchymal stromal cells through MMP-mediated proteolytic cleavage. (crcm-marseille.fr)
  • Using blocking antibodies, we demonstrate that the inhibition of T cell proliferation occurs through cell-to-cell interactions implicating PD-1 receptor expressed on T cells and its ligands, PD-L1 and PD-L2, on fibroblasts. (crcm-marseille.fr)
  • The Protein Tyrosine Phosphatase SHP-1 (PTPN6) but Not CD45 (PTPRC) Is Essential for the Ligand-Mediated Regulation of CD22 in BCR-Ligated B Cells. (bvsalud.org)
  • My results show that treatment of colon cancer cells with Foxy-5, a WNT5A mimicking peptide, leads to up-regulation of 15-PGDH through JNK/AP-1 pathway. (lu.se)
  • Flt3 ligand is critically involved in generation of early and common lymphoid progenitors but not in the regulation of the size of the hematopoietic stem cell pool. (ox.ac.uk)
  • Altogether these results indicate that small variations in cell purity can significantly alter T cell reactions to TLR ligands. (mingsheng88.org)
  • This study stresses the importance of a stringent purification method when investigating the part of microbial ligands in T cell function. (mingsheng88.org)
  • The first described CID systems involve microbe-derived dimerizing ligands, such as rapamycin, that direct protein neo-associations that rewire eukaryotic cell signaling 5 . (nature.com)
  • Involved in cell-cycle regulation. (biolegend.com)
  • Involved in the stimulation of B- and T-cell function and the regulation of humoral immunity. (lu.se)
  • Transient transfection of intracellular Notch1 (Notch1-IC) into a pre-B cell line resulted in the down-regulation of EBF-regulated promoters and diminished the capacity of EBF to activate these promoters in an epithelial cell line. (lu.se)
  • Plants sense abscisic acid (ABA) using chemical-induced dimerization (CID) modules, including the receptor PYR1 and HAB1, a phosphatase inhibited by ligand-activated PYR1. (nature.com)
  • This system is unique because of the relative ease with which ligand recognition can be reprogrammed. (nature.com)
  • In the auxin and jasmonic acid systems, ligand recognition is shared between protein-binding partners. (nature.com)
  • CD22 dephosphorylation by SHP-1 appears to be augmented by homotypic CD22 clustering mediated by recognition of CD22 as a ligand of CD22 because CD22 clustering increases the number of nearby CD22. (bvsalud.org)
  • This Funding Opportunity Announcement (FOA) supports SBIR applications in the service of improved ligands and imaging technologies for investigating brain function and enhancing disease diagnosis and treatment of SUD and HIV/AIDS. (nih.gov)
  • More research is needed to improve the ability of existing imaging ligands and technologies (e.g., analytical programs) for non-invasive imaging of brain function such that changes from disease or other insults to the brain can be better tracked, and the response to pharmacological interventions can be better interpreted. (nih.gov)
  • OBJECTIVES: To determine the function of the angiopoietin (Ang)-Tie ligand-receptor system, and to assess the effect of Tie1-751, a naturally occurring extracellular domain of the Tie1 receptor derived by alternative splicing, in an in vivo model of RA. (ox.ac.uk)
  • We will group genes into pathways to identify likely targets of Rv3651 regulation. (ssgcid.org)
  • We suggest that MMP-dependent cleavage of PD-1 ligands on fibroblasts may limit their immunosuppressive capacity and thus contribute to the exacerbation of inflammation in tissues. (crcm-marseille.fr)
  • WISP3-dependent regulation of type II collagen and aggrecan production in chondrocytes. (medlineplus.gov)
  • This is done by taking a mutant protein (naturally occurring or selectively engineered), which is activated by a different ligand (carefully synthesized or selected). (wikipedia.org)
  • Selectively altering the ligand-binding domain to make it orthogonal to the natural ligand-receptor interface, as well as the making the DNA-binding domain and hormone response element orthogonal, would give a researcher precise control of a gene's transcription in order to study a gene's action. (wikipedia.org)
  • In the projects described in this thesis, I report results of X-ray crystallographic and computational molecular docking experiments to investigate aspects of the regulation of gelsolin by ATP, PIP₂ and calcium ions. (ubc.ca)
  • This article intends to give an educational overview on the current status of PSMA ligand PET imaging, including imaging procedure and interpretation, clinical indications, diagnostic potential, and impact on treatment planning. (snmjournals.org)
  • In the present work, accelerated methods for the comparison of protein binding sites as well as an extended procedure for the assessment of ligand poses in protein binding sites are presented. (uni-marburg.de)
  • Using a human monocyte-derived DC (moDC) model, we have examined the relationship between DC VDR expression and the impact of exposure to its ligand, 1 alpha 25(OH)(2)D(3). (birmingham.ac.uk)
  • Further, there are considerable limitations to many of the currently available imaging ligands, including poor selectivity, high cost, or risks from radiation exposure in the case of pediatric populations. (nih.gov)
  • CONCLUSIONS: Our data demonstrate that the Ang-Tie ligand-receptor system is dysregulated in CIA. (ox.ac.uk)
  • The reversal of charged interactions is similar, but it involves switching the position of the positive charge and the negative charge on the protein and ligand. (wikipedia.org)
  • The intention here is that the orthogonal ligand will not interact with the original protein. (wikipedia.org)
  • The original protein will also be designed to not interact with the orthogonal ligand in certain cases. (wikipedia.org)
  • Mutations in the CD40 ligand (CD40L) are responsible for human hyper immunoglobulin M (IgM) syndrome. (nki.nl)
  • While the ligands for E- and L-selectins with primary binding activity have not been identified so far, the functionally most important ligand for P-selectin has been identified. (biovendor.com)
  • Davis L, Chen Y, Sen M. WISP-3 functions as a ligand and promotes superoxide dismutase activity. (medlineplus.gov)
  • the development of ligands or imaging technologies to enable visualization of latent or replicating HIV viruses within the brain, 3. (nih.gov)
  • Both STARD12 and STARD14 were corelated with epigenetic regulation, especially TP53 mutation and m6A modification. (medsci.org)
  • Extended molecular dynamics simulations (0.1 micros), employed here to characterize the factors controlling diatomic ligand diffusion through the apolar tunnel system, suggest that O2 migration in deoxy-trHbN is restricted to a short branch of the tunnel, and that O2 binding to the heme drives conformational and dynamical fluctuations promoting NO migration through the long tunnel branch. (ub.edu)
  • STARD12 and STARD14 were expected to be potential biomarkers for LUAD, which were associated with epigenetic regulation, immune infiltration and ferroptosis. (medsci.org)