• Receptor tyrosine kinases (RTKs) are a vital element in regulating many intracellular signal transduction pathways. (wikipedia.org)
  • Several pathways of phagocytic signal transduction have been identified [ 3345 ], including the activation of tyrosine kinases or serine/threonine kinase C, leading to phosphorylation of the receptors and other proteins which are recruited at the sites of phagocytosis. (nanomedicine.com)
  • In many cases there are two or more pathways that must be simultaneously inhibited, although in a few cases these pathways may share a common inhibitor [ 3348 ]. (nanomedicine.com)
  • However, the host intracellular signaling pathways and the molecular mechanisms associated with Acanthamoeba -mediated HBMEC cytotoxicity have not been determined. (asm.org)
  • More specifically, substrates with certain FYVE domains (named after the first four proteins in this motif, Fab1, YotB, Vac1p, and EEA1) bind PIP, and these pathways have been implicated in vesicular trafficking or receptor-mediated endocytosis ( 5 ). (asm.org)
  • While previous studies have shown that AT2R is expressed by nociceptors in human DRG (hDRG), and that EMA401 inhibits capsaicin responses in cultured hDRG neurons, the expression and levels of its endogenous ligands AngII and AngIII in clinical neuropathic pain tissues, and their signalling pathways, require investigation. (ox.ac.uk)
  • EMA401 may act on paracrine/autocrine mechanisms at peripheral nerve terminals, or intracrine mechanisms, to reduce neuropathic pain signalling in AngII/NGF/TRPV1-convergent pathways. (ox.ac.uk)
  • The central participant in Wnt pathways is usually a cytoplasmic proteins, the beta-catenin, whose balance initiates the transcription of Wnt-target genes. (research-in-field.com)
  • Ras can also regulate autophagy by affecting several signaling pathways including the mTOR pathway. (oncotarget.com)
  • Ras signaling is a major junction of various signaling pathways. (oncotarget.com)
  • What pathways are this gene/protein implicaed in? (cancer-genetics.org)
  • The signaling is mediated by Ras/Mapk, PI3K/Akt, c-Src and STAT3/5 and include cell proliferation, reduced apoptosis, altered cytoskeletal function and more. (wikipedia.org)
  • Similar findings were made in bone marrow cells from gene-targeted mice lacking Bim and/or Puma infected with FLT3-ITD and treated with inhibitor, where loss of Puma only provided transient protection from apoptosis, but loss of Bim preserved clonal survival upon FLT3-ITD inhibition. (ashpublications.org)
  • By this basic mechanism, protein kinases mediate most of the signal transduction in eukaryotic cells, regulating cellular metabolism, transcription, cell cycle progression, cytoskeletal rearrangement and cell movement, apoptosis, and differentiation. (antiviralbiologic.com)
  • aegypti in which the mosquitoes express an inactive form of Michelob_x (Mx), an antagonist of the Inhibitor of Apoptosis (IAP), to induce apoptosis in those cells in which actively replicating DENV-2 is present. (bvsalud.org)
  • Both spontaneous apoptosis and apoptosis in response to treatment with staurosporine or doxorubicin were investigated. (biomedcentral.com)
  • While spontaneous apoptosis was similar in ALK+ ALCL cell lines expressing either GzB or control shRNA, GzB shRNA-expressing cells were less sensitive to staurosporine or doxorubicin-induced apoptosis as evidenced by reduced PARP cleavage and decreased DNA fragmentation. (biomedcentral.com)
  • GzB primarily initiates apoptosis either through direct proteolytic processing and activation of initiator (caspase 8) or executioner (caspases 3 and 7) caspases, or through disruption of mitochondrial outer membrane potential via cleavage of the Bid protein [ 2 ]. (biomedcentral.com)
  • GzB may also contribute to apoptosis induction through the cleavage of other cellular substrates including nuclear lamin B, poly (ADP-ribose) polymerase (PARP), and inhibitor of caspase-activated DNase (ICAD) [ 2 ]. (biomedcentral.com)
  • Apoptosis regulatory proteins are delicately balanced. (bmj.com)
  • The key regulator of this process, hypoxia inducible factor 1 (HIF-1), can initiate apoptosis by inducing high concentrations of proapoptotic proteins, such as BNIP3, and can cause stabilisation of p53. (bmj.com)
  • The tumor suppressor p53 is recognized as a critical regulator of cell cycle progression and apoptosis, incorporating signals from DNA damage and other cellular stressors to decide cell fate [ 1 ]. (biomedcentral.com)
  • By Western blot, this antibody recognizes a 116 kDa protein which corresponds to PARP and the 85 kDa apoptosis-induced cleavage product of prICE and CPP32 from rat thymus extract. (thermofisher.com)
  • Proteolysis of PARP to its stable 85kDa fragment is an early marker of programmed cell death (apoptosis) and is mediated by the caspase CPP32 protein. (thermofisher.com)
  • This is why targeting the HGF/c-MET signalling pathway has been untaken as a treatment for cancer, and several different therapeutic approaches are being clinically tested. (wikipedia.org)
  • Inactivation of the PI3-kinase pathway, but not of Ras-mitogen-activated protein (MAP) kinase signaling, was essential to elicit cytotoxic responses. (ashpublications.org)
  • The latter indicated the presence of an intracellular urocortin-induced signal transduction pathway that is unique to keratinocytes. (biologists.com)
  • Purpose To investigate the consequences of norrin, a non-conventional ligand for Wingless-Int (Wnt)-beta-catenin signaling pathway, about protease-mediated death of transformed rat retinal ganglion cells (RGC-5). (research-in-field.com)
  • Although norrin triggered the Wnt pathway, Dickkopf related proteins 1 (Dkk1), an inhibitor of Wnt/beta-catenin pathway, didn't completely stop norrins neuroprotective results. (research-in-field.com)
  • Latest studies have recommended that norrin functions as a ligand for WinglessCInt (Wnt) receptor-beta-catenin transmission pathway, although norrin doesn't have series homology for the Wnt category of proteins [3]. (research-in-field.com)
  • A significant difference between norrin and Wnts is usually that norrin activates Wnt/beta-catenin transmission transduction pathway by particularly getting together with Frizzled-4 receptors, while Wnts can bind to multiple Frizzled receptors. (research-in-field.com)
  • This tumor cell characteristic demonstrates, partly, a dysregulation of the total amount between pro-apoptotic and anti-apoptotic BCL-2 protein [7] that regulate the intrinsic mitochondrial apoptotic pathway. (islamophobiacon.com)
  • Targeting the ATP binding site of c-Met by small molecules inhibitors is one strategy for inhibition of the tyrosine kinase. (wikipedia.org)
  • Since FTS is a non toxic drug we hypothesized that FTS and chloroquine (an autophagy inhibitor) will synergize in cell growth inhibition and cell death. (oncotarget.com)
  • Description: Measuring inhibition of kinase activity in a biochemical assay. (guidetomalariapharmacology.org)
  • The protein kinase family is one of the largest families of proteins in eukaryotes, classified in 8 major groups based on sequence comparison of their tyrosine ,PTK) or serine/threonine ,STK) kinase catalytic domains. (antiviralbiologic.com)
  • AngII and, as expected, NGF significantly increased signal intensity of p38 and p42/44 MAPK, which was reversed by EMA401. (ox.ac.uk)
  • Activated Ras transmits signals through its interaction with multiple effectors, including mitogen activated kinase (MAPK), phosphoinositide-3-kinase (PI3K) and Ral-GEF [ 1 , 2 ]. (oncotarget.com)
  • A variety of approaches have been used to target c-Met, each focusing on one of the serial steps that regulate c-Met activation by antibodies, peptide agonists, decoy receptors and other biologic inhibitors or small molecules inhibitors. (wikipedia.org)
  • Receptors able to mediate phagocytosis are expressed almost exclusively in neutrophils, monocytes and macrophages, and receptor clustering is thought to occur upon particle binding which in turn generates a phagocytic signal, activating the phagocytic process [ 3345 ]. (nanomedicine.com)
  • Monomeric GTPases of the Rho and ARF families which are engaged downstream of activated receptors, in cooperation with phosphatidylinositol 4-phosphate 5-kinase and phosphatidylinositol 3-kinase lipid modifying enzymes, can modulate locally the assembly of the submembranous actin filament system leading to particle internalization [ 3345 , 5261 ]. (nanomedicine.com)
  • Wnts, a family group of around 20 secreted glycoproteins, initiate intracellular transmission transduction by binding concurrently to two cell surface area receptors: a Frizzled (Fzd) receptor and an associate from the low-density lipoprotein receptor-related proteins (LRP) family members, LRP-5 or LRP-6 [7,8]. (research-in-field.com)
  • Whenever a Wnt isn't destined to Fzd and LRP receptors, glycogen synthase kinase-3 (GSK-3) phosphorylates beta-catenin and focuses on it to degradation in the proteosomes. (research-in-field.com)
  • The Ras family of small GTPases transmits signals initiated by cell surface receptors, to regulate several cellular processes such as cell growth, differentiation, motility and death [ 1 ]. (oncotarget.com)
  • Growth factor cytokine receptors typically have intrinsic kinase activity. (openrheumatologyjournal.com)
  • In contrast, classical immune (type I/ II) cytokine receptors do not have intrinsic protein kinase activity but associate with the Janus family of kinases (JAKs). (openrheumatologyjournal.com)
  • The beta chain contains the intracellular tyrosine kinase domain and a tail on the C-terminal which is vital for the docking of substrates and downstream signalling. (wikipedia.org)
  • The majority of inositol lipids reside in membranes and serve as substrates for kinases, phosphatases, and phospholipases. (asm.org)
  • Next, we observed that Acanthamoeba specifically activates phosphatidylinositol 3-kinase. (asm.org)
  • Acanthamoeba -mediated brain endothelial cell death was abolished using LY294002, a phosphatidylinositol 3-kinase inhibitor. (asm.org)
  • These results were further confirmed using brain microvascular endothelial cells expressing dominant negative forms of phosphatidylinositol 3-kinase. (asm.org)
  • This is the first demonstration that Acanthamoeba -mediated brain microvascular endothelial cell death is dependent on phosphatidylinositol 3-kinase. (asm.org)
  • Phosphatidylinositol 3-kinases (PI3Ks) are important signaling molecules that phosphorylate the 3′ OH position of the inositol ring of phosphoinositides (PIs), generating the second messengers PI(3)P, PI(3,4)P 2 , and PI(3,4,5)P 3 ( 4 , 17 ). (asm.org)
  • It is a member of a group of key signaling molecules that share a carboxyl-terminal domain related to phosphatidylinositol-3-kinase but unlike many family members, it lacks kinase activity. (biomedcentral.com)
  • The Ras family of small GTPases transmits extracellular signals that regulate cell growth, differentiation, motility and death. (oncotarget.com)
  • High and stable ATP levels prevent aberrant intracellular protein aggregation in yeast. (waseda.jp)
  • In my laboratory researchers are examining the roles played by axonal cytoskeletal proteins in nervous system development, and in the etiology of Alzheimer's and other related neurodegenerative diseases. (uml.edu)
  • Rapamycin may be a potent and specified inhibitor of mTOR, a crucial effector of activated PIK3CA/AKT signaling and it is currently used in the clinic. (pafr-inhibitor.com)
  • These inhibitors may have therapeutic application in the treatment of various types of cancers. (wikipedia.org)
  • c-Met is a receptor tyrosine kinase, which can cause a wide variety of different cancers, such as renal, gastric and small cell lung carcinomas, central nervous system tumours, as well as several sarcomas when its activity is dysregulated. (wikipedia.org)
  • Ras signaling is constitutively active in a large number of human cancers. (oncotarget.com)
  • c-Met inhibitors are a class of small molecules that inhibit the enzymatic activity of the c-Met tyrosine kinase, the receptor of hepatocyte growth factor/scatter factor (HGF/SF). (wikipedia.org)
  • Met tyrosine kinase is the receptor for hepatocyte growth factor (HGF), also known as scatter factor (SF). (wikipedia.org)
  • Its N-terminal region binds to Met and receptor dimerization as well as autophosphorylation of two tyrosines occur in the activation loop (A-loop) in the kinase domain of Met. (wikipedia.org)
  • Receptor tyrosine kinase inhibitors targeting FLT3 have developed as attractive treatment options. (ashpublications.org)
  • FLT3 (FMS-like tyrosine kinase 3) is a type III receptor tyrosine kinase (RTK) closely related to the platelet-derived growth factor (PDGF) receptor and c-Kit with important functions in the regulation of early hematopoietic cells. (ashpublications.org)
  • Thrombin cleaves its G-protein-linked seven-transmembrane domain receptor, thereby releasing a 41-aa peptide and generating a new amino terminus that acts as a tethered ligand for the receptor. (umassmed.edu)
  • T cell receptor beta (TCR-β) rearrangement and expression Staurosporine datasheet of CD69 are hallmarks of T-cell development, but expression of both was virtually absent in CD39tg DP thymocytes (Fig. 4B). (cetp-signal.com)
  • Upon cytokine activation receptor chain- bound STATs are then phosphorylated on the tyrosine residues, which results in dimerisation of STAT proteins that translocate to the nucleus and activate gene transcription. (openrheumatologyjournal.com)
  • Both the intermediate and high affinity forms of the receptor are involved in receptor-mediated endocytosis and transduction of mitogenic signals from interleukin 2. (cancer-genetics.org)
  • Provided these multiple activities, the primary system where gossypol induces cell loss of life in virtually any particular tumor type will probably vary, with regards to the known degrees of anti-apoptotic BCL-2 proteins as well as other tumor cell-specific elements. (islamophobiacon.com)
  • Poly ADP-Ribose Polymerase (PARP) uses nicotinamide adenine dinucleotide (oxidized form) NAD as a substrate to catalyse the transfer of ADP-ribose to a variety of nuclear protein acceptors. (thermofisher.com)
  • FDA approval PARP inhibitor Our results indicate that the downregulation of RhoGDI alpha similarly affects the in vitro migration and invasion of ER+ MCF7 and ER- MDA-MB-231 cells. (pdgfrsignals.com)
  • 20 crystal structures with and without ligands have been published and in 2010 nearly a dozen small molecule c-Met inhibitors have been tested clinically. (wikipedia.org)
  • Here, we have determined the growth-inhibitory and proapototic mechanisms of 2 small molecule inhibitors of FLT3, AG1295 or PKC412, in hematopoietic progenitor cells, human leukemic cell lines, and primary AML cells expressing FLT3-ITD. (ashpublications.org)
  • Small molecule Jak inhibitors as therapeutic agents have become a reality and the palette of such inhibitors will likely expand. (openrheumatologyjournal.com)
  • For example, in the figure showing trypanothione reductase from the human protozoan parasite Trypanosoma cruzi, two molecules of an inhibitor called quinacrine mustard are bound in its active site. (pdgfrsignals.com)
  • Protein kinases are enzymes that transfer a phosphate group from a phosphate donor onto an acceptor amino acid in a substrate protein. (antiviralbiologic.com)
  • Metabolic fitness relies on the functionality of heat shock proteins (HSPs), molecular chaperones that facilitate the correct folding of metabolism enzymes and their assembly in macromolecular structures. (biomedcentral.com)
  • This review will summarize our current knowledge on these key enzymes and their associated pharmaceutical inhibitors. (openrheumatologyjournal.com)
  • Addition of the protein kinase C (PKC) activator, 12-O-tetradecanoylphorbol 13-acetate (TPA), or the Ca 2+ ionophore, ionomycin, mimicked the profile of GnRH-induced α and LH β mRNA elevation. (bgu.ac.il)
  • Activator of protein kinase A (cyclic AMP agonist). (biolog.de)
  • Because relapses occur after initial responses, identification of FLT3-ITD-mediated signaling events are important to facilitate novel therapeutic interventions. (ashpublications.org)
  • Discovery of non-genotoxic mechanisms through which p53 protein may be activated within tumor cells harboring wild-type p53 remains an important therapeutic objective, both in effort to alleviate traditional off-target chemotherapeutic side-effects and to prevent the unpredictable mutagenicity characteristic of these therapies. (biomedcentral.com)
  • Since cells alter their metabolic rewiring during tumorigenesis and along cancer progression, targeting key metabolic players and metabolism-associated proteins represents a valuable approach with a high therapeutic potential. (biomedcentral.com)
  • Risk-DEGs were shown to be associated with immune modulation and tumor immune evasion, as well as defense systems, signal transduction, the tumor microenvironment, and immunoregulation. (biomedcentral.com)
  • The data show p53 protein was transcriptionally activated and contributed to NGF-mediated neurite outgrowth during differentiation of PC12 cells. (biomedcentral.com)
  • Despite data supporting the transcriptional activity of p53 protein in differentiation, few genetic targets have been described and fewer still within a neuronal context. (biomedcentral.com)
  • The interacting genes are involved in a range of cellular processes including gene expression, mitochondrial function, and membrane sorting/protein trafficking. (biomedcentral.com)
  • Genes involved in transcription, RNA processing, mitochondrial function and membrane sorting/protein trafficking were prevalent. (biomedcentral.com)
  • The first one is located in an activation loop in the centre of the kinase domain. (embl.de)
  • Synaptic Signals from Glutamate-Treated Neurons Induce Aberrant Post-Synaptic Signals in Untreated Neuronal Networks. (uml.edu)
  • Spontaneous neuronal signaling is inherently musical and mathematical: insight into the universal human affinity for music. (uml.edu)
  • Autophagy is a process that regulates the balance between protein synthesis and protein degradation. (oncotarget.com)
  • FTS acts as a functional Ras antagonist in cells, affecting Ras-membrane interactions by dislodging the protein from its anchorage domains, facilitating its degradation and, thus, reducing cellular active Ras content [ 8 , 9 ]. (oncotarget.com)
  • As a transcription factor, many of the functional cellular roles of the p53 protein are elicited through direct DNA binding to sequence-specific cis-regulatory elements [ 3 ] leading to the transactivation or transrepression of target genes. (biomedcentral.com)
  • Many key cellular metabolic processes are dependent on the functionality of heat shock proteins (HSPs) [ 14 ]. (biomedcentral.com)
  • Adenosine triphosphate (ATP) at millimolar levels has recently been implicated in the solubilization of cellular proteins. (waseda.jp)
  • We herein demonstrated that AMP-activated protein kinase (AMPK) and adenylate kinase (ADK) cooperated to maintain cellular ATP levels regardless of glucose levels. (waseda.jp)
  • The present study demonstrates that cellular ATP homeostasis ensures proteostasis and revealed that suppressing the high volatility of cellular ATP levels prevented cytotoxic protein aggregation, implying that AMPK and ADK are important factors that prevent proteinopathies, such as neurodegenerative diseases. (waseda.jp)
  • Several inhibitors have been described, such as AG1295, CEP701, PKC412, and SU-11 248, with cytotoxic effects to cell lines and primary AML cells in vitro expressing mutant FLT3. (ashpublications.org)
  • Single-cell imaging of ATP-reduced yeast mutants revealed that ATP levels in these mutants underwent stochastic and transient depletion, which promoted the cytotoxic aggregation of endogenous proteins and pathogenic proteins, such as huntingtin and α-synuclein. (waseda.jp)
  • Later, series of more selective c-Met inhibitors were designed, where an indolin-2-one core (encircled in figure 1) was present in several kinase inhibitors. (wikipedia.org)
  • Using information from the co-crystal structure of PHA-66752 and c-Met, the selective inhibitor PF-2341066 was designed. (wikipedia.org)
  • Development of RTK inhibitors selective for FLT3 has emerged as attractive drugs for treatment of AML patients. (ashpublications.org)
  • SU-11274 was evolved by substitution at the 5-position of the indolinone and by adding a 3,5-dimethyl pyrrole group, PHA-665752 was evolved - a second-generation inhibitor with better potency and activity. (wikipedia.org)
  • A hierarchal cluster analysis revealed that the pattern of SSL interactions for tra1 SRR 3413 most closely resembles deletions of a group of regulatory GTPases required for membrane sorting/protein trafficking. (biomedcentral.com)
  • We present that AT101 induces appearance of BCL-2/E1B-19K-interacting proteins 3 (BNIP3), an atypical BH3-just proteins, which promotes AT101-induced cell loss of life. (islamophobiacon.com)
  • Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. (embl.de)
  • Strategies Materials Dulbeccos altered Eagles moderate (DMEM), Dulbeccos phosphate buffered saline (DPBS), penicillin, and streptomycin had been from Invitrogen Company (Carlsbad, CA). Staurosporine was from Alexis Biochemicals (NORTH PARK, CA). Human being glu-plasminogen (item #410) and 914913-88-5 human being fibrinogen (item #431) were from American Diagnostica (Stamford, CT). (research-in-field.com)
  • n\nResults: Production IWR-1-endo of recombinant protein was confirmed by SDS-PAGE. (rafinhibitors.com)
  • The kinase domain usually consists of a bi-lobed structure, where the lobes are connected with a hinge region, adjacent to the very conserved ATP binding site. (wikipedia.org)
  • We analysed the intra-individual deviation between both measurements and GNS-1480 in vivo signal-to-noise ratio (SNR) as a marker for signal quality. (pdgfrsignals.com)
  • K252a was the first structure to be solved in complex with the unphosphorylated MET kinase domain. (wikipedia.org)
  • Cell-bound or soluble protein A produced by Staphylococcus aureus [ 1728 ] attaches to the Fc region of IgG and blocks the cytophilic (cell-binding) domain of the antibody. (nanomedicine.com)
  • Several structures of the AGC-kinase C-terminal domain have been solved. (embl.de)
  • Taxonomic distribution of proteins containing S_TK_X domain. (embl.de)
  • The complete taxonomic breakdown of all proteins with S_TK_X domain is also avaliable . (embl.de)
  • Click on the protein counts, or double click on taxonomic names to display all proteins containing S_TK_X domain in the selected taxonomic class. (embl.de)
  • The protein contains one AP2 domain. (or.jp)
  • PKC412 is one of several FLT3 inhibitors that is currently evaluated in late-stage clinical trials in AML patients carrying FLT3 mutations. (ashpublications.org)