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TyrosineThreoninePhosphorylationSerineAmino Acid SequenceProtein-Serine-Threonine KinasesMolecular Sequence DataProtein Tyrosine PhosphatasesEnzyme ActivationPhosphoproteinsProtein KinasesCell LinePhosphotyrosinePhosphoserineThreonine DehydrataseSignal TransductionTyrosine 3-MonooxygenaseCells, CulturedPhosphothreonineProtein BindingEnzyme InhibitorsMutationOxidative PhosphorylationProtein-Tyrosine KinasesPhosphopeptidesKineticsProto-Oncogene ProteinsProtein Kinase CTransfectionPhosphoprotein PhosphatasesProto-Oncogene Proteins c-aktBinding SitesBlotting, WesternCyclic AMP-Dependent Protein KinasesMitogen-Activated Protein KinasesIntracellular Signaling Peptides and ProteinsMutagenesis, Site-DirectedPeptide MappingRecombinant ProteinsProtein Processing, Post-TranslationalProtein Structure, TertiaryCalcium-Calmodulin-Dependent Protein KinasesPrecipitin TestsPhosphatidylinositol 3-KinasesVanadatesAdaptor Proteins, Signal TransducingRecombinant Fusion ProteinsProtein Kinase InhibitorsBase SequenceSubstrate SpecificityProtein Tyrosine Phosphatase, Non-Receptor Type 11Casein Kinase IIMitogen-Activated Protein Kinase 1ProteinsCOS CellsImmunoblottingCell Line, TumorOkadaic AcidReceptor Protein-Tyrosine Kinases3T3 CellsDNA-Binding ProteinsImmunoprecipitationMitogen-Activated Protein Kinase 3src Homology DomainsCalciumElectrophoresis, Polyacrylamide GelHeLa CellsProtein Phosphatase 2Glycogen Synthase Kinase 3Focal Adhesion Protein-Tyrosine KinasesTumor Cells, CulturedProtein Tyrosine Phosphatase, Non-Receptor Type 6MAP Kinase Signaling SystemReceptor, Epidermal Growth FactorGenisteinSequence Homology, Amino AcidPaxillinsrc-Family KinasesModels, BiologicalProto-Oncogene Proteins pp60(c-src)Focal Adhesion Kinase 1IsoenzymesMembrane ProteinsExtracellular Signal-Regulated MAP KinasesAmino Acid SubstitutionCarrier ProteinsProtein Phosphatase 1Proto-Oncogene Proteins c-fynProtein Tyrosine Phosphatase, Non-Receptor Type 1Cell Cycle ProteinsApoptosisTime FactorsEpidermal Growth FactorProtein TransportLymphocyte Specific Protein Tyrosine Kinase p56(lck)Adenosine TriphosphateCell Nucleusp38 Mitogen-Activated Protein KinasesAmino AcidsCDC2 Protein Kinase
ResiduesKinasesProteinsKinase activityReceptorPhosphorylatePathwaysEGFRProtein kinaseInhibitorNovel phosphorylationCancersPathwayDownstreamStimulationCytoplasmicActivationSmall moleculeAntibodyPeptidePhosphataseMyeloidEnhancesRegulationY317OGG1MediatesCaseinTumorigenesisMechanismConformationGlycosylationCellRegulate2021TranscriptionInhibitsSitesSpecificityTumor
Residues17
  • Cytokine binding to the cell surface leads to phosphorylation of the receptor complex by receptor associated Janus kinases (JAKs) at tyrosine residues. (nature.com)
  • OGT transfers O-GlcNAc moieties from UDP-GlcNAc to serine and threonine residues of proteins and O-GlcNAcase (OGA) catalyzes the opposite reaction to remove O-GlcNAc. (nature.com)
  • The method, named Predikin, identifies key conserved substrate-determining residues in the kinase catalytic domain that contact the substrate in the region of the phosphorylation site and so determine the sequence surrounding the phosphorylation site. (biomedcentral.com)
  • Predikin now consists of two components: (i) PredikinDB, a database of phosphorylation sites that links substrates to kinase sequences and (ii) a Perl module, which provides methods to classify protein kinases, reliably identify substrate-determining residues, generate scoring matrices and score putative phosphorylation sites in query sequences. (biomedcentral.com)
  • New features in Predikin include the use of SQL queries to PredikinDB to generate predictions, scoring of predictions, more reliable identification of substrate-determining residues and putative phosphorylation sites, extended options to handle protein kinase and substrate data and an improved web interface. (biomedcentral.com)
  • The post-translational modification of proteins by phosphorylation of serine, threonine or tyrosine residues is a ubiquitous process in cellular regulation. (biomedcentral.com)
  • Crystal structures of protein kinases with bound substrate peptides show that substrate residues at positions -3 to +3 relative to the phosphorylated serine, threonine or tyrosine residue adopt an extended conformation and bind to a pocket in the catalytic domain of the protein kinase [ 8 ]. (biomedcentral.com)
  • IRS-1 is phosphorylated on serine, threonine and tyrosine residues in a variety of tissues. (thermofisher.com)
  • Two tyrosine residues, Y317 and Y508, are identified on PIK3CA/p110α. (biomedcentral.com)
  • For example, phosphorylation mainly occurs on a subset of three types of amino acids, including serine (S), threonine (T) and tyrosine (Y). Methylation is predominantly found on lysine (K) and arginine (R) residues. (deepdyve.com)
  • One of the regulatory mechanisms that modulate the Cdk5 kinase activity is phosphorylation of conserved residues ( Dhavan and Tsai, 2001 ). (frontiersin.org)
  • The reversible phosphorylation of proteins on serine, threonine, and tyrosine residues represents a fundamental strategy used by eukaryotic organisms to regulate a host of biological functions, including DNA replication, cell cycle progression, energy metabolism, and cell growth and differentiation. (rupress.org)
  • This phosphorylation is usually directed to serine/threonine residues in the cytoplasmic tail and third cytoplasmic loop but rarely on tyrosine residues. (massorrerjazzbar.com)
  • GPCRs can also undergo Tyr-phosphorylation on B-Raf-inhibitor 1 residues located in the cytoplasmic domain name [13]. (massorrerjazzbar.com)
  • EGF treatment inhibited GPRC5A-mediated repression of anchorage-independent growth via phosphorylation of these tyrsoine sites since the same treatment failed to do so on GPRC5A-4?F mutant, in which tyrosine residues were replaced with phenylalanine (F). IHC analysis with specific antibody to Y317/Y320-P site showed that GPRC5A in NSCLC tissues is mostly phosphorylated, whereas GPRC5A in adjacent tumor tissues is mostly non-phosphorylated. (massorrerjazzbar.com)
  • Phosphorylated on threonine and serine residues. (bomiprot.org)
  • The role of kinases is to phosphorylate serine, threonine, or by Microwave-Assisted Suzuki tyrosine residues of speci﫿c protein substrates via the transfer of the -phosphate group of Coupling. (sagepub.com)
Kinases15
  • We have previously described an approach to predicting the substrate specificity of serine-threonine protein kinases. (biomedcentral.com)
  • Protein kinases, the enzymes responsible for protein phosphorylation, make up almost 2% of protein-encoding genes in the human genome [ 1 ] and an estimated 30-50% of human proteins are phosphorylated [ 2 ]. (biomedcentral.com)
  • Normally, upon the stimulations by growth factors (GFs), the receptor tyrosine kinases (RTKs) are activated, and then recruit PI3K protein complex on the membrane to generate phosphatidylinositol-3,4,5-triphosphate (PIP3) from phosphatidylinositol-4,5-biophosphate (PIP2) [ 2 ]. (biomedcentral.com)
  • PIP3 phosphatase PTEN is inactivated upon phosphorylation in its C-terminal region by several serine/threonine kinases [ 12 ]. (biomedcentral.com)
  • Cyclin-dependent kinase 5 (Cdk5) is a member of the Cdk family of serine/threonine kinases and is abundantly expressed in the brain ( Dhavan and Tsai, 2001 ). (frontiersin.org)
  • The phosphorylation of IκBα by IκB kinase family have been so many identified, but the phosphorylation sites of IκBα by other kinases remain poorly understood. (researchsquare.com)
  • Levels of cellular protein phosphorylation are modulated both by protein kinases and phosphatases. (rupress.org)
  • To fully understand this complex and essential regulatory process, the kinases and phosphatases mediating the changes in cellular phosphorylation must be identified and characterized. (rupress.org)
  • The Ser/Thr phosphorylation by GPCR kinases (GRKs) leads to the internalization of GPCRs [10, 11] and hampers GPCR signaling [12]. (massorrerjazzbar.com)
  • EGFR and its family members are the major groups of receptor tyrosine kinases that are aberrantly activated in many NSCLCs [15]. (massorrerjazzbar.com)
  • Moreover, EGF and TGF-, ligands of EGFR, are frequently expressed in NSCLCs, which provides an autocrine mechanism to sustain the hyper-activation of these receptor tyrosine kinases (RTKs) [19]. (massorrerjazzbar.com)
  • Because 14-3-3 proteins bind to specific phosphoserine-containing sequences they are likely to have an important role in signaling pathways mediated by serine/threonine protein kinases. (icbinhibitor.com)
  • It has been shown that S338 phosphorylation on RAF1 is carried out via autophosphorylation and via phosphorylation by PAKs (p21-activated kinases) [17 18 19 20 RAF kinases in turn activate the MEK/ERK cascade which was recently found to be rapidly activated by LSA [12]. (biomedigs.org)
  • With the advent of cloning, it swiftly became clear not simply that that this was a large family members, but also that it integrated kinases that could phosphorylate tyrosine at the same time as serine and threonine [80]. (5htreceptor.com)
  • Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. (icr.ac.uk)
Proteins7
Kinase activity1
Receptor8
  • IRS-1 contains three putative binding sites for 14-3-3 (Ser 270, Ser 374 and Ser 641) and the motif around Ser 270 is located in the phosphortyrosine binding domain of IRS-1, which is responsible for the interaction with the insulin receptor. (thermofisher.com)
  • Concomitant activation of the insulin-like growth factor-1 receptor, Akt, and extracellular signal-regulated protein kinase 1 and 2 as well as increased phosphorylation of Bad also were unique to the hippocampus of APP Sw mice. (jneurosci.org)
  • Glutamate inputs activate Cdk5, which inhibits postsynaptic dopamine D1 receptor (D1R)-mediated signaling by phosphorylating DARPP-32 at Thr75 (Thr75-DARPP-32) in the striatum, since DARPP-32 with Thr75 phosphorylation (DARPP-32-pThr75) functions as an inhibitor of cAMP-dependent protein kinase A (PKA). (frontiersin.org)
  • Here, we show that in the mouse striatum, dopamine receptor stimulation negatively regulates phosphorylation of Tyr15-Cdk5 most likely through a D2R-mediated mechanism. (frontiersin.org)
  • For example, cytokine-induced tyrosine phosphorylation of CXCR4, which reduces the level of functional CXCR4 on cell surface, contributes to GRK3 and -arrestin2-mediated sequestration of this receptor in the cytoplasm [14]. (massorrerjazzbar.com)
  • 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)
  • 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)
  • One potential candidate identified from the screen was EphA2 a cell surface receptor tyrosine kinase implicated in development stem cell niche maintenance and cancer progression (14). (researchatlanta.org)
Phosphorylate1
  • c-Abelson tyrosine kinase (c-Abl) is known to phosphorylate Cdk5 at Tyr15 (Tyr15-Cdk5) and thereby facilitates the Cdk5 activity. (frontiersin.org)
Pathways8
EGFR8
  • In this study, we showed that EGFR interacts with and phosphorylates GPRC5A in two highly conserved double-tyrosine modules (Y317/Y320 and Y347/Y350) at the C-terminal domain name of GPRC5A. (massorrerjazzbar.com)
  • Thus, EGFR-mediated tyrosine phosphorylation represents a newly identified mechanism by which the tumor suppressive function of GPRC5A is usually inactivated in lung cancer. (massorrerjazzbar.com)
  • Tyrosine phosphorylation of GPRC5A, identified using the PY99 antibody, was significantly increased in cells expressing EGFR. (massorrerjazzbar.com)
  • However, in the absence of EGFR expression, no tyrosine-phosphorylation of GPRC5A was detected even after 6?hr EGF treatment (right panel, Physique? (massorrerjazzbar.com)
  • Thus, the EGF-induced tyrosine phosphorylation of GPRC5A is usually mediated through EGFR. (massorrerjazzbar.com)
  • To investigate B-Raf-inhibitor 1 whether GPRC5A is usually a direct target of EGFR tyrosine kinase, we co-expressed EGFR and myc-tagged GPRC5A in HEK293T cells. (massorrerjazzbar.com)
  • In addition, clathrin-mediated EGFR internalization induced by inflammatory cytokines and UV irradiation depends on MAPK14-mediated phosphorylation of EGFR itself as well as of RAB5A effectors. (icr.ac.uk)
  • Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. (icr.ac.uk)
Protein kinase3
  • The second messenger PIP3 recruits and activates 3-phosphoinositide dependent protein kinase-1 (PDK1) and AKT serine/threonine kinase on the membrane [ 2 ]. (biomedcentral.com)
  • This resulted in the recognition of RAF1 a serine/threonine protein kinase that plays a key role in the Ras/MAPK signaling pathway. (biomedigs.org)
  • As inactive This article is an open access article protein kinase conformations exhibit greater structural variation than the conserved active distributed under the terms and conformation to which Type I PKIs bind, Type II PKIs are considered potentially more conditions of the Creative Commons selective than Type I ones [13,14]. (sagepub.com)
Inhibitor6
  • Moreover, in the 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine (MPTP) mouse model, dopamine deficiency caused increased phosphorylation of both Tyr15-Cdk5 and Thr75-DARPP-32 in the striatum, which could be attenuated by administration of L-3,4-dihydroxyphenylalanine and imatinib (STI-571), a selective c-Abl inhibitor. (frontiersin.org)
  • Background: The phosphorylation of NF-kappaB inhibitor alpha (IκBα) protein is pivotal to the regulation of NF-κB transcription factor activity in the cell. (researchsquare.com)
  • It has been suggested that tyrosine phosphorylation B-Raf-inhibitor 1 of GPCR is required for Src recruitment and subsequent Ser/Thr phosphorylation by GRK. (massorrerjazzbar.com)
  • Protein phosphorylation is also involved in the global control of Zambon, A. Expedient Access to DNA replication during the cell cycle, as well as in the mechanisms that cope with stress- Type II Kinase Inhibitor Chemotypes induced replication blocks [1]. (sagepub.com)
  • Figure 1 Comprehensive phosphoproteomics identifies an invasive motile signaling signature associated with BRAF inhibitor resistance Ligand-independent EphA2 signaling drives the adoption of an invasive phenotype Despite EphA2 being implicated in the suppression of cell adhesion and migration following stimulation with ephrin-A1 it can also function in a forward signaling ligand-independent manner following phosphorylation by AKT at S897. (researchatlanta.org)
  • For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. (icr.ac.uk)
Novel phosphorylation2
Cancers1
  • The amino acid variation S326C of human OGG1 disrupts Ser-326 phosphorylation site and affects susceptibility to a variety of cancers [9]. (deepdyve.com)
Pathway3
Downstream1
Stimulation3
Cytoplasmic1
Activation3
  • 7 The JAKs also trigger the activation and tyrosine phosphorylation of STAT5, causing parallel dimerization, nuclear translocation and tetramerization of STAT5. (nature.com)
  • These data indicate that tuberin deficiency in angiomyolipoma enhances mTOR activation by phosphorylation of S6K and downregulation of protein and mRNA expression of OGG1 resulted in accumulation of oxidized DNA in patients with TSC. (biomedcentral.com)
  • MAPK14 interacts also with casein kinase II, leading to its activation through autophosphorylation and further phosphorylation of TP53/p53. (icr.ac.uk)
Small molecule1
  • Furthermore to selectivity worries, ATP-competitive inhibitors must cope with intracellular ATP amounts that are usually in the millimolar range, as the ATP activity.30 These features make the discovery of small molecule substrate phosphorylation site inhibitors highly desirable. (careersfromscience.org)
Antibody1
  • Phospho-p27 Kip1 (Thr198) Antibody detects endogenous levels of p27 Kip1 only when phosphorylated at Threonine 198. (affbiotech.cn)
Peptide2
  • In an un-biased whole cell phospho-peptide analysis, GPRC5A was identified as one of the tyrosine phosphorylated protein in HER2-overexpressing HMEC cells after EGF or heregulin (HRG) treatment [20, 21]. (massorrerjazzbar.com)
  • Levels of peptide phosphorylation were quantified using MaxQuant and the protein-protein interactions characterized using GeneGO (18 19 Cytoscape mapping of the global signaling changes showed an increase in both the number of nodes and the number of edges in vemurafenib SAR131675 resistant 1205Lu cells (Na?ve: 544 nodes 1208 edges. (researchatlanta.org)
Phosphatase4
  • STP, serine/threonine protein phosphatase. (rupress.org)
  • PCC can be induced by cell fusion between interphase and mitotic cells or by the action of chemicals mainly phosphatase inhibitors such as for example calyculin A or okadaic acidity [14]. (biomedigs.org)
  • Binds to a kinase interaction motif within the protein tyrosine phosphatase, PTPRR (By similarity). (icr.ac.uk)
  • Furthermore, pyrin interacts with proline-serine-threonine phosphatase-interacting protein (PSTPIP1), also known as CD2-binding protein 1 (CD2BP1), which is a tyrosine-phosphorylated protein involved in cytoskeletal organization and thereby involved in immunologic cellular interactions. (medscape.com)
Myeloid2
  • Our data show that O-GlcNAcylation of STAT5 is an important process that contributes to oncogenic transcription through enhanced STAT5 tyrosine phosphorylation and oligomerization driving myeloid transformation. (nature.com)
  • The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. (icr.ac.uk)
Enhances1
  • This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. (icr.ac.uk)
Regulation1
  • The importance of protein phosphorylation as a regulatory mechanism was 1st found together with the pioneering work of Krebs and Fischer and the regulation of Glycogen phosphorylase by phosphorylase kinase [3,4]. (5htreceptor.com)
Y3171
OGG12
  • The increase in tuberin phosphorylation and the decrease tuberin expression are associated with decrease in OGG1 protein and mRNA levels in tumor samples compared to normal kidney samples. (biomedcentral.com)
  • The gene coding for the DNA repair enzyme that recognizes and excises 8-oxo-dG is 8-oxoG-DNA glycosylase (OGG1) [ 14 ]. (biomedcentral.com)
Mediates1
Casein2
Tumorigenesis1
Mechanism1
Conformation1
Glycosylation1
  • N-linked glycosylation affects asparagine (N), and O-linked glycosylation occurs on the hydroxyl group of either serine (S) or threonine (T) [3]. (deepdyve.com)
Cell3
  • phosphoinositide-dependent kinase 2 (PDK2) is a serine/threonine kinase that is important for regulating cell cycle. (wikipedia.org)
  • The low and high LSA concentration allowed 10 and 4 cell population doublings during the 24 and 14 days of drug treatment respectively. (biomedigs.org)
  • Protein phosphorylation in eukaryotes plays a key role in cell signaling, gene expres- Gobbi, A. (sagepub.com)
Regulate1
  • Protein phosphorylation can regulate enzyme function, mediate protein-protein interactions, alter subcellular localization, and control protein stability. (rupress.org)
20211
Transcription1
Inhibits1
Sites5
Specificity1
  • Specificity: Recognizes human beta, gamma, sigma and zeta isoforms of 14-3-3. (icbinhibitor.com)
Tumor1
  • The significant increase of phospho-tuberin expression is associated with increase phosphorylation of S6K in tumor samples compared to controls. (biomedcentral.com)