• Wild type as well as substrate-trapping DA forms of PTPϵM suppressed phosphorylation of IR downstream enzymes such as Akt, extracellular regulated kinase (ERK) and glycogen synthase kinase 3 (GSK3). (bioone.org)
  • Moreover, a comparison of the apo- and inhibitor-bound Lyp structures reveals that the Lyp-specific region S 35 TKYKADK 42 , which harbors a PKC phosphorylation site, could adopt either a loop or helical conformation. (elsevierpure.com)
  • We demonstrate that Ser-35 phosphorylation impairs Lyp's ability to inactivate the Src family kinases and down-regulate T cell receptor signaling. (elsevierpure.com)
  • Dovitinib also stimulated the translocation of phosphorylated Smad1/5/8 into the nucleus and phosphorylation of mitogen-activated protein kinases, including ERK1/2 and p38. (molcells.org)
  • Tyrosine phosphorylation of the N-methyl-D-aspartate receptor is enhanced in synaptic membrane fractions of the adult rat hippocampus. (ox.ac.uk)
  • It is well documented that tyrosine kinases increase NMDAR phosphorylation and potentiate NMDAR function. (ox.ac.uk)
  • We therefore hypothesized that tyrosine phosphorylation of the NMDAR may enhance the trafficking of the receptor to the synaptic membrane. (ox.ac.uk)
  • Here, we show that the stoichiometry of NR2A and NR2B tyrosine phosphorylation is significantly higher in synaptosomal membranes than intracellular microsomal/light membranes. (ox.ac.uk)
  • Interestingly, NR2B tyrosine-1472, but not NR1 serine-896 or -897, phosphorylation is significantly higher in synaptosomal membranes than intracellular microsomal/light membranes. (ox.ac.uk)
  • Furthermore, treatment of hippocampal slices with either a tyrosine phosphatase inhibitor or a tyrosine kinase inhibitor alters NMDAR tyrosine phosphorylation and produces a corresponding change in the concentration of NMDARs in the synaptosomal membrane fraction. (ox.ac.uk)
  • Taken together, these data support the hypothesis that tyrosine phosphorylation may enhance NMDAR activity by increasing the number of NMDARs at the synaptic membrane. (ox.ac.uk)
  • Intersecting analysis, molecular docking, and pathway validation analysis showed that risperidone influences the adipocytokine signaling pathway by targeting MAPK14 (mitogen-activated protein kinase 14), MAPK8 (mitogen-activated protein kinase 8), and RXRA (retinoic acid receptor RXR-alpha), thereby inhibiting long-chain fatty acid β-oxidation by decreasing STAT3 (signal transducer and activator of transcription 3) expression and phosphorylation. (frontiersin.org)
  • Together with PROTEIN-TYROSINE KINASE, it regulates tyrosine phosphorylation and dephosphorylation in cellular signal transduction and may play a role in cell growth control and carcinogenesis. (bvsalud.org)
  • In recent years, the search for intracellular signaling integrator downstream of receptor tyrosine kinases provided valuable novel substrates. (springer.com)
  • The insulin receptor (IR) and JAK1 tyrosine kinases and STAT3 can serve as direct substrates for the T-cell protein tyrosine phosphatase (TCPTP). (diabetesjournals.org)
  • Dovitinib (TKI258) is a small molecule multi-kinase inhibitor currently in clinical phase I/II/III development for the treatment of various types of cancers. (molcells.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)
  • On the other hand, the C-terminal which is the cytoplasmic domain of TLRs has a homology with interleukin type-1 receptor (IL-1R), known as Toll 1L-1R receptor (TIR) domain [11]. (fortunejournals.com)
  • Prospective screening for inhibitory agents was performed for the protease HtrA from the human pathogen H. pylori using a homology model of the target protein. (uni-frankfurt.de)
  • Although the molecular mechanisms responsible for the selective vulnerability of these cells are not well understood, activation of the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway has been implicated in neuroprotective responses to excitotoxicity in other neuronal populations. (jneurosci.org)
  • Along these lines, accumulating evidence shows that the p42/44 mitogen-activated protein kinase (MAPK) pathway plays an important role in neuronal cell survival. (jneurosci.org)
  • Identification of a novel inhibitor of mitogen-activated protein kinase kinase. (rndsystems.com)
  • The Structural Basis for the Selectivity of Benzotriazole Inhibitors of Ptp1B. (expasy.org)
  • Protein-tyrosine phosphatase 1B (PTP1B) has been implicated as an important regulator in several signaling pathways including those initiated by insulin and leptin. (johnshopkins.edu)
  • Potent and specific PTP1B inhibitors could serve as useful tools in elucidating the physiological functions of PTP1B and may constitute valuable therapeutics in the treatment of several human diseases. (johnshopkins.edu)
  • We have determined the crystal structure of PTP1B in complex with compound 2, the most potent and selective PTP1B inhibitor reported to date. (johnshopkins.edu)
  • Here, a recently introduced serial sample-support chip system has been used to obtain the first SSX structure of a human phosphatase, specifically protein tyrosine phosphatase 1B (PTP1B) in the unliganded (apo) state. (iucr.org)
  • Overall, our results illustrate the promise of serial methods for room-temperature crystallography, as well as future avant-garde crystallography experiments, for PTP1B and other proteins. (iucr.org)
  • Here we investigate a series of 2, 5-disubstituted oxadiazole as novel PTP1B inhibitor. (ajptonline.com)
  • Epidermal growth factor receptor and the adaptor protein Shc were reported to be substrates of this PTP, which suggested the roles in growth factor mediated cell signaling. (wikipedia.org)
  • Some members of the serpin family may be substrates rather than inhibitors of SERINE ENDOPEPTIDASES, and some serpins occur in plants where their function is not known. (lookformedical.com)
  • Protein-protein interaction (PPI) networks and modules were constructed to identify hub genes with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and Cytoscape. (researchsquare.com)
  • GO analysis revealed that the DEGs were enriched in biological processes related to inflammation, and the enriched pathways in the KEGG pathway analysis were cytokine-cytokine receptor interaction, chemokine signalling pathway and NF-κB signalling pathway. (researchsquare.com)
  • In addition, interaction with estrogen receptors has been demonstrated, leading to inhibition of function. (cancerindex.org)
  • In the absence of SAP, interaction of CD48 on EBV-infected cells with 2B4 (a receptor belonging to the immunoglobulin superfamily that is found on natural killer [NK] cells as well as a small subset of T cells) on NK cells inhibits their ability to kill the EBV-infected cell. (medscape.com)
  • The most widely studied TLR associated with LPS ligand binding, interaction and downstream activation, is TLR-4. (fortunejournals.com)
  • Methodology/Principal Findings: We present a method for structure-based virtual screening that is based on the comprehensive prediction of ligand binding sites on a protein model and automated construction of a ligand-receptor interaction map. (uni-frankfurt.de)
  • Identification and Characterization of MortaparibPlus - A Novel Triazole Derivative That Targets Mortalin-p53 Interaction and Inhibits Cancer-Cell Proliferation by Wild-Type p53-Dependent and -Independent Mechanisms (2021). (edu.in)
  • Among these negative regulators, protein tyrosine phosphatases (PTPs) are likely to play a pivotal role in IR signaling. (bioone.org)
  • Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of tyrosine-phosphorylated proteins and are negative regulators of tyrosine kinase receptor mediated signaling. (ajptonline.com)
  • Unexpectedly, we find that excitotoxicity provokes an early inactivation of PKD1 through a dephosphorylation-dependent mechanism mediated by protein phosphatase-1 (PP1) and dual specificity phosphatase-1 (DUSP1). (nature.com)
  • Together with James P. Allison, who worked on another co-inhibitory receptor called cytotoxic T-lymphocyte-associated Protein 4 (CTLA-4), Tasuku Honjo was awarded the Nobel Prize in Physiology or Medicine 2018 for the discovery of cancer therapy by inhibition of negative immune regulation ( Wolchok, 2018 ). (frontiersin.org)
  • They are distinguished from INDIRECT THROMBIN INHIBITORS, such as HEPARIN, which act by enhancing the inhibitory effects of antithrombins. (lookformedical.com)
  • COVID19-inhibitory activity of withanolides involves targeting of the host cell surface receptor ACE2: insights from computational and biochemical assays (2021). (edu.in)
  • Immunoblot analysis revealed an insulin-like glucose transporting mechanism of AEG by activating key markers involved in the insulin signaling cascade such as insulin receptor beta IRβ, insulin receptor substrate1, 85 phosphatidyl inositol 3′ kinase (PI3K) and PKB. (wiley.com)
  • Among them are the Sprouty proteins which mainly act as inhibitors of growth factor-dependent neuronal and glial signaling pathways. (springer.com)
  • Impaired insulin receptor (IR) signaling leads to insulin resistance and type 2 diabetes mellitus. (bioone.org)
  • Here, we report that high levels of the striatal-enriched protein tyrosine phosphatase (STEP), a key regulator of ERK/MAPK signaling, are found in vulnerable somatostatin-immunoreactive hilar interneurons. (jneurosci.org)
  • Information regarding the molecular events underlying cell type-specific vulnerability may be gained by the analysis of inherent neuroprotective signaling responses actuated by excitotoxic stimuli. (jneurosci.org)
  • Codiscovery by other groups led to the other designations, DSHP and SAP (signaling lymphocytic activation molecule [SLAM]-associated protein). (medscape.com)
  • Therefore, elucidating key signaling markers and their role in different types of cancers is a pre-requisite. (fortunejournals.com)
  • Although it has been reported that GCA modulates Toll-like receptor 9 (TLR9)-mediated signaling via direct conversation with TLR9 [29], a genetic knockout of in mice failed to show relevant phenotypes and the physiological role of GCA remains to be elucidated [30]. (abic2004.org)
  • Protein kinase C regulates human pluripotent stem cell self-renewal. (rndsystems.com)
  • Taken together, targeting Sprouties as intracellular inhibitors of the ERK pathway holds great promise for the treatment of various neurological disorders including gliomas. (springer.com)
  • Glycans, either alone or complexed with glycan-binding proteins, can deliver intracellular signals or control extracellular processes that promote initiation, execution and resolution of cell death programs. (nature.com)
  • It is also related to increased adiponectin (APN) expression associated with adipocyte differentiation, as well as the expression of adipogenic genes such as peroxisome proliferator-activated receptor ( PPAR) ( 22 , 23 ). (frontiersin.org)
  • A gain of function screen for genes that enable proliferation independently of matrix anchorage identified a cell adhesion molecule PVRL4 (poliovirus-receptor-like 4), also known as Nectin-4. (elifesciences.org)
  • What pathways are this gene/protein implicaed in? (cancerindex.org)
  • These results suggest that effects of β1 on sodium channel gating are dependent on the genetic background and signal transduction pathways present in the cell type used in heterologous expression and emphasize the importance of analyzing the effects of β1 in vivo . (jneurosci.org)
  • We review clinical data on the benefit of RASi in primary and metastatic tumors and propose that, by activating immunostimulatory pathways, these inhibitors can enhance immunotherapy of cancer. (nutriforce.cn)
  • There she led a team of 6 chemists performing lead optimization on a macrocycle inhibitor of the hedgehog protein which resulted in analogs with superior potency, improved metabolic stability, excellent in vivo pharmacokinetics and no in vitro safety liabilities. (harvard.edu)
  • In this review, we summarized different effective management strategies to address weight loss, such as bariatric surgery and several classes of drugs, namely metformin, GLP-1 receptor agonists, amylin analogs, and SGLT2 inhibitors. (bvsalud.org)
  • MEK inhibitors: the chemistry and biological activity of U0126, its analogs, and cyclization products. (rndsystems.com)
  • In general, the immunoassays tested were able to detect their intended fentanyl analog and some closely related analogs, but more structurally diverse analogs, including 4-methoxy-butyryl fentanyl and 3-methylfentanyl, were not well detected. (cdc.gov)
  • In general, analogs with group additions to the piperidine, or bulky rings or long alkyl chain modifications in the N-aryl or alkyl amide regions, were poorly detected compared to other types of modifications. (cdc.gov)
  • Clinical studies have shown that blocking the PD-1 pathway is effective against several types of cancer including melanoma, lymphoma, lung, and renal cancer ( Sanmamed and Chen, 2018 ). (frontiersin.org)
  • Given the stringent, cell type-specific regulation of this pathway, these data raise the possibility that vulnerability to SE-induced cell death may, in part, depend on the capacity of a cell to elicit a MAPK pathway-dependent neuroprotective response. (jneurosci.org)
  • Our data reveal that the vulnerable cells express high levels of striatal-enriched protein tyrosine phosphatase (STEP), which is a key regulator of the extracellular signal-regulated kinase (ERK) pathway. (jneurosci.org)
  • Previous studies have demonstrated that glycolysis inhibitors reduce the proliferation of non‑small cell lung cancer (NSCLC) cells by interfering with the aerobic glycolytic pathway. (spandidos-publications.com)
  • This is associated with dephopshorylation of crucial tyrosine residues within the CD3 complex and CD28. (frontiersin.org)
  • An enzyme group that specifically dephosphorylates phosphotyrosyl residues in selected proteins. (bvsalud.org)
  • Structural and mutational analyses indicate that the inhibitor binds both the active site and a nearby peripheral site unique to Lyp, thereby furnishing a solid foundation upon which inhibitors with therapeutic potency and selectivity can be developed. (elsevierpure.com)
  • So it is a potential therapeutic target for insulin resistance associated with obesity and type 2 diabetes. (ajptonline.com)
  • Programmed cell death protein (PD-1) and its ligands play a fundamental role in the evasion of tumor cells from antitumor immunity. (frontiersin.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)
  • Retrospective validation studies demonstrate the superiority of methods which combine both shape and pharmacophore information on the family of peroxisome proliferator-activated receptors (PPARs). (uni-frankfurt.de)
  • A mutation (C121W) in the extracellular Ig domain of β1 causes generalized epilepsy with febrile seizures plus type 1 (Wallace et al. (jneurosci.org)
  • During the progression of colitis, genetic alterations associated with mucosal permeability [ e.g. those in extracellular matrix protein 1 ( ECM1 ), cadherin 1 ( CDH1 ), and hepatocyte nuclear factor 4 alpha ( HNF4A )] have been observed and considered to confer the risk of severe UC ( 11 , 12 ). (iiarjournals.org)
  • Extracellular protease inhibitors that are secreted from FIBROBLASTS. (lookformedical.com)
  • On-Chip Preconcentration Microchip Capillary Electrophoresis Based CE-PRM-LIVE for High-Throughput Selectivity Profiling of Deubiquitinase Inhibitors. (harvard.edu)
  • Tyrosine-protein phosphatase non-receptor type 2 is an enzyme that in humans is encoded by the PTPN2 gene. (wikipedia.org)
  • Angiotensin-converting enzyme (ACE) converts Ang I into angiotensin II (Ang II) which acts on an angiotensin type 1 (AT1) and angiotensin type 2 (AT2) receptor. (hindawi.com)
  • Intrinsic brain RAS is an enzyme-neuropeptide system having functional components (angiotensinogen, peptidases, angiotensin, and specific receptor proteins) with important biological and neurobiological activities in the brain. (hindawi.com)
  • An enzyme that catalyzes the hydrolysis of proteins, including elastin. (lookformedical.com)
  • The enzyme breaks down elastin, the specific protein of elastic fibers, and digests other proteins such as fibrin, hemoglobin, and albumin. (lookformedical.com)
  • On the contrary, knockdown of Sprouty proteins increases proliferation of activated astrocytes and, consequently, reduces secondary brain damage in neuronal lesion models such as kainic acid-induced epilepsy or endothelin-induced ischemia. (springer.com)
  • Philips and Felix [ 4 ] proved the presence of Ang II-activated neurons in the brain and subfornical organs [ 4 ]. (hindawi.com)
  • Here, we describe a method to detect microcystins in human plasma by using immunocapture followed by a protein phosphatase inhibition assay. (cdc.gov)
  • Their response involves antigen capture, enhancing their MHC-II presentation receptors and production of chemokines and/or cytokines at the site of inflammation [9]. (fortunejournals.com)
  • Diabetes mellitus is a metabolic disorder characterized by hyperglycaemia and alterations in carbohydrate, lipid, and protein metabolism, associated with absolute or relative deficiencies in insulin secretion and/or insulin action [ 1 ]. (hindawi.com)
  • In this work a chemoenzymatic approach has been implemented for the preparation of the marine metabolite (+)-Harzialactone A. The synthesis involved a stereoselective, biocatalyzed reduction of the prochiral ketone 4-oxo-5-phenylpentanoic acid or the corresponding esters, all generated by chemical reactions. (bvsalud.org)
  • Synthesis of Novel Protein Tyrosine Phosphatases 1b inhibitors 2, 5-disubstituted oxadiazole. (ajptonline.com)
  • Reduced expression of phosphatase PTPN2 promotes pathogenic conversion of Tregs in autoimmunity. (ucsd.edu)
  • However, over recent years, it became clear that RTKs cannot be sufficiently activated by growth factors or receptor agonists in the adult and aging brain to exert significant neuroprotective or neurorestorative effects. (springer.com)
  • Risperidone-induced weight gain is associated with a number of factors, including gene polymorphisms ( 12 - 14 ), exercise ( 15 - 17 ), peripheral molecules ( 18 ), and hyperphagia caused by regulating the expression of melanocortin-4 receptor (MC4R), neuropeptide Y (NPY), and agouti-related peptide (AgRP) ( 19 - 21 ). (frontiersin.org)
  • Two decades later, pioneering studies suggested that lectin-like molecules constitutively expressed on the surface of macrophages can selectively recognize changes on glycans decorating the surface of apoptotic thymocytes, 4 , 5 although these studies likewise did not provide substantial insight into the mechanisms by which lectin-glycan interactions regulate cell death. (nature.com)
  • In innate immunity, immune cells are activated by their pattern recognition receptors (PRRs), which bind to pattern molecules of invading pathogens. (fortunejournals.com)
  • Background Olfactory receptors work at the interface between the chemical world of volatile molecules and the perception of scent in the brain. (uni-frankfurt.de)
  • The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. (lookformedical.com)
  • The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. (wikipedia.org)
  • Different mutations of EDA gene and EDAR gene could make different influence on the protein function and lead to the occurrence of HED. (bvsalud.org)
  • The lymphoid-specific tyrosine phosphatase (Lyp) has generated enormous interest because a single-nucleotide polymorphism in the gene (PTPN22) encoding Lyp produces a gain-of-function mutant phosphatase that is associated with several autoimmune diseases, including type I diabetes, rheumatoid arthritis, Graves disease, and systemic lupus erythematosus. (elsevierpure.com)
  • 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)
  • What does this gene/protein do? (cancerindex.org)
  • XLP type 2 (XLP2) is caused by mutations in the XIAP gene. (medscape.com)
  • XLP2 is caused by mutations in the inhibitor-of-apoptosis gene XIAP . (medscape.com)
  • They found that the gene that codes for a protein called poliovirus receptor-like 4 (PVRL4) allows attachment-free cell growth and also makes cells cluster together once detached from the matrix. (elifesciences.org)
  • over the years, various medicinal plants and their extracts have been reported to be effective in the treatment of diabetes [ 4 ]. (hindawi.com)
  • Insulin resistance is a key pathophysiological feature of type 2 diabetes. (wiley.com)
  • Obesity and type 2 diabetes (T2DM) are major public health concerns associated with serious morbidity and increased mortality. (bvsalud.org)
  • Type 2 diabetes has reached epidemic proportions, afflicting roughly 170 million people worldwide. (diabetesjournals.org)
  • Here, we report the identification of a bidentate salicylic acid-based Lyp inhibitor I-C11 with excellent cellular efficacy. (elsevierpure.com)
  • Unlike other SGAs, such as clozapine and olanzapine, risperidone is a derivative of benzisoxazole with multiple receptor antagonist properties, making it more effective against negative symptoms and more beneficial on both affective symptoms and cognitive impairments ( 11 ). (frontiersin.org)
  • Characterization of the brain penetrant neuropeptide Y Y 2 receptor antagonist SF-11. (rndsystems.com)
  • Risperidone upregulates fatty acid synthase (FASN) and sterol regulatory element-binding protein 1 (SREBP1) expression in hepatocyte cultures and mouse liver by targeting the hepatic SREBP-1c/FASN couple, which is also one of the mechanisms by which risperidone induces weight gain ( 24 ). (frontiersin.org)
  • Targeting Receptor-Type Protein Tyrosine Phosphatases with Biotherapeutics: Is Outside-in Better than Inside-Out? (westminster.ac.uk)
  • AT1, AT2, AT4, and mitochondrial assembly receptor (MasR) are found to be plentiful in the brain. (hindawi.com)
  • Metformin, a known inhibitor of mitochondrial OXPHOS, has been indicated to reduce NSCLC morbidity and mortality in clinical studies. (spandidos-publications.com)
  • In a prospective study, we virtually screen a large compound library for cyclooxygenase inhibitors, using a self-organizing map as a pre-filter and the shape descriptor for candidate prioritization. (uni-frankfurt.de)
  • Demographic and that this particular family of angiogenic clinical data were collected during routine proteins plays an important role in placental obstetric visits. (who.int)
  • U0126 is a potent and selective non-competitive inhibitor of MAP kinase kinase. (rndsystems.com)
  • This observation argues for additional nuance in interpreting the nature of allosteric coupling in this protein. (iucr.org)
  • Glucose transporter 4 translocation was confirmed by determining the uptake of glucose in the presence of insulin receptor tyrosine kinase and PI3K inhibitors. (wiley.com)
  • PD-L1 is expressed not only by all hematopoietic cells but also by many non-hematopoietic cell types such as endothelial cells and epithelial cells ( Sharpe and Pauken, 2018 ). (frontiersin.org)
  • Herein, we investigated the effect of dovitinib on human recombinant bone morphogenetic protein (BMP)-2-induced osteoblast differentiation in a cell culture model. (molcells.org)
  • Herein, we review the role of glycans and glycan-binding proteins as essential components of the cell death machinery during physiologic and pathologic settings. (nature.com)
  • Glycosylation of classical death receptors fine-tunes cell death programs. (nature.com)
  • At that time, glycobiology, which is the study of carbohydrates and their recognition by motif-specific carbohydrate-binding proteins or lectins, lagged far behind the studies that defined the structural and cellular biology of cell death. (nature.com)
  • There are primarily two types of lung cancer: Non-small cell lung cancer (NSCLC) and SCLC, and the former accounts for ~85% of all lung cancer cases ( 3 ). (spandidos-publications.com)
  • This versatile cell type orchestrates a broad spectrum of biological functions and exerts very complex and even opposing functions on cell death, immune stimulation or suppression, and angiogenesis, resulting in an overall pro- or antitumoral effect. (nutriforce.cn)
  • Epithelial tissue is one of the four major types of tissue found in animals, and is the only type of tissue that is able to form and maintain layers of cells that are just one cell thick. (elifesciences.org)
  • also showed that interactions between the PVRL4 in one cell and a related protein called PVRL1 in a neighboring cell were responsible for holding the cells together in clusters. (elifesciences.org)
  • The aim of this study was to investigate the role and specific mechanism of the actin-interacting protein zyxin (ZYX) in HCC. (techscience.com)
  • However, the detailed mechanism of Fra-1 in GC is unclear, such as the identification of Fra-1-interacting proteins and their role in GC pathogenesis. (techscience.com)