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Protein-Serine-Threonine KinasesDual-Specificity PhosphatasesProtein-Tyrosine KinasesMitogen-Activated Protein Kinase PhosphatasesProtein Tyrosine PhosphatasesDual Specificity Phosphatase 1Sp Transcription FactorsSubstrate SpecificityProtein Kinase CSp1 Transcription FactorProtein KinasesMolecular Sequence DataAmino Acid SequenceDual Specificity Phosphatase 6Sequence Homology, Amino AcidDual Specificity Phosphatase 3Base SequenceSp3 Transcription FactorSp4 Transcription FactorPhosphorylationCalcium-Calmodulin-Dependent Protein KinasesCyclic AMP-Dependent Protein KinasesSp2 Transcription FactorMitogen-Activated Protein KinasesMAP Kinase Signaling Systemp38 Mitogen-Activated Protein KinasesPlicamycinMitogen-Activated Protein Kinase KinasesEnzyme ActivationProtein Kinase InhibitorsSignal TransductionMitogen-Activated Protein Kinase 1Phosphatidylinositol 3-KinasesBinding SitesJNK Mitogen-Activated Protein KinasesPromoter Regions, GeneticMitogen-Activated Protein Kinase 3Cell LineProtein BindingSensitivity and SpecificityGene Expression Regulation, EnzymologicPhosphoprotein PhosphatasesCell Line, TumorProtein Kinase C-alphaTransfectionProtein Kinase C-deltaKineticsTranscription, GeneticBlotting, WesternProtein Phosphatase 1RNA, MessengerMutationCells, CulturedRecombinant Fusion ProteinsAMP-Activated Protein KinasesEnzyme InhibitorsMutagenesis, Site-DirectedGene Expression RegulationIsoenzymesCloning, MolecularProtein Kinase C-epsilonProtein Kinase C betasrc-Family KinasesMAP Kinase Kinase 1Recombinant ProteinsTetradecanoylphorbol AcetateMAP Kinase Kinase 4Cyclic GMP-Dependent Protein KinasesDNA PrimersDown-RegulationProtein Structure, TertiarySerineTranscription FactorsRNA, Small Interferingortho-AminobenzoatesHeLa CellsExtracellular Signal-Regulated MAP KinasesElectrophoretic Mobility Shift Assaycdc25 PhosphatasesCDC2 Protein KinaseDNA-Binding ProteinsCyclic AMPTriterpenesCasein Kinase IITranscriptional ActivationPhosphoric Monoester HydrolasesCalcium-Calmodulin-Dependent Protein Kinase Type 2Cell Cycle ProteinsMAP Kinase Kinase KinasesTyrosineCell ProliferationMAP Kinase Kinase 7Antibody SpecificityThreonineReverse Transcriptase Polymerase Chain ReactioneIF-2 KinaseProtein Tyrosine Phosphatases, Non-Receptorp21-Activated KinasesCalciumChromatin Immunoprecipitation
PhosphataseSerineCatalytic domainPhosphatasesMAPKMitogen-ActivatInhibitorsGenesHighly conservedGeneMEK1DYRK1ASubstrateReceptor tyrosiCyclin-dependPathwaysIntracellularArabidopsisInactivateEvolutionarilyPhosphorylation-regulatedInhibitorGlycogenTransmembrane receptorPTKsSubfamilyReceptorsProto-oncogeneMAPK1ResiduesMetabolismBiochemistrySequence similarityInteractionsEndoplasmic reticulumVitroKinomePlay important roles
Phosphatase20
Serine9
  • In biochemistry, a dual-specificity kinase (EC 2.7.12.1) is a kinase that can act as both tyrosine kinase and serine/threonine kinase. (wikipedia.org)
  • We have previously examined the specificities of 28 commercially available compounds, reported to be relatively selective inhibitors of particular serine/threonine-specific protein kinases [Davies, Reddy, Caivano and Cohen (2000) Biochem. (nih.gov)
  • HIPKs belong to the CMGC group of serine/threonine kinases and are part of the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family. (nature.com)
  • DYRKs are named after their characteristic dual-specificity, as they auto-phosphorylate a conserved tyrosine in their activation loop, but phosphorylate substrates on serine and threonine residues 2 . (nature.com)
  • C-terminally adjacent to the HID follows a proline, glutamate, serine, and threonine (PEST)-rich domain, mediating proteasomal degradation of these kinases. (nature.com)
  • 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 PTKc family is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). (unl.edu)
  • Non-specific serine/threonine protein kinase. (uma.es)
  • Rho-associated protein kinases (ROCKs) are serine-threonine kinases contain isoforms ROCK1 and ROCK2. (cancer-research-network.com)
Catalytic domain5
Phosphatases13
  • These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. (hatinhibitor.com)
  • Levels of cellular protein phosphorylation are modulated both by protein kinases and phosphatases. (rupress.org)
  • Although the importance of kinases in this process has long been recognized, an appreciation for the complex and fundamental role of phosphatases is more recent. (rupress.org)
  • Through extensive biochemical and genetic analysis, we now know that pathways are not simply switched on with kinases and off with phosphatases. (rupress.org)
  • Furthermore, kinases and phosphatases may work together to modulate the strength of a signal. (rupress.org)
  • Adding further complexity to this picture is the fact that both kinases and phosphatases can function in signaling networks where multiple kinases and phosphatases contribute to the outcome of a pathway. (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)
  • A variety of approaches, including biochemical purification, gene isolation by homology, and genetic screens, have been successfully used for the identification of putative protein kinases and phosphatases. (rupress.org)
  • Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. (embl.de)
  • Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. (antibodies-online.com)
  • Tyrosine specific protein phosphatases (PTPases) contain two conserved cysteines, the second one has been shown to be absolutely required for activity. (embl.de)
  • This domain can be found in dual specificity phosphatases. (embl.de)
  • The deduced amino acid sequence of PPS1p shows similarity with protein-tyrosine phosphatases (PTPases) and is most closely related to a subfamily of PTPases that are capable of dephosphorylating phosphoseryl and phosphothreonyl residues as well as phosphotyrosyl residues. (embl.de)
MAPK6
  • Mitogen-activated protein kinase (MAPK) cascades transmit environmental signals and induce stress and defence responses in plants. (biorxiv.org)
  • They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. (antibodies-online.com)
  • Activation occurs through phosphorylation at Ser 271 and Thr 275 by several upstream MAPK kinase kinases (MAP3Ks). (rndsystems.com)
  • This protein is part of a signaling pathway called the RAS/MAPK pathway, which transmits chemical signals from outside the cell to the cell's nucleus. (medlineplus.gov)
  • The genetic changes abnormally activate the protein, which disrupts the tightly regulated RAS/MAPK signaling pathway in many types of cells. (medlineplus.gov)
  • The mutations lead to the production of a version of the protein that is overactive, which increases RAS/MAPK signaling in bone tissue. (medlineplus.gov)
Mitogen-Activat1
Inhibitors10
  • Many kinases in these pathways are validated drug targets and kinase inhibitors are first-line treatment for several advanced cancers. (escholarship.org)
  • The first generation of kinase inhibitors were intended to target single proteins. (escholarship.org)
  • However, the highly conserved active sites of protein kinases prohibited the design of perfectly selective inhibitors. (escholarship.org)
  • Unexpectedly, this specificity problem led to the development of clinically useful, multi-targeted kinase inhibitors. (escholarship.org)
  • The design of dual PI3K/PTK inhibitors is chemically challenging because PI3Ks and PTKs are members of significantly divergent kinase families. (escholarship.org)
  • A screen of 72 inhibitors against 456 human kinases. (guidetomalariapharmacology.org)
  • A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfiler TM service. (guidetomalariapharmacology.org)
  • A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase Hotspot SM platform. (guidetomalariapharmacology.org)
  • Therefore, identifying other V600E-BRAF kinase inhibitors is very significant for cancer research (Roskoski 2012 ). (springeropen.com)
  • Selective compounds have been developed that target either the extracellular ligand-binding region of the EGFR (including a number of monoclonal antibodies [MAbs], immunotoxins, and ligand-binding cytotoxic agents) or the intracellular tyrosine kinase region (including various small-molecule inhibitors). (medscape.com)
Genes6
  • In this study, we identified dual specificity protein kinase TTK (TTK) as the most up-regulated and differentially expressed kinase encoding genes in GSCs. (oncotarget.com)
  • Such radiations include genes involved in spermatogenesis, chemosensation, Wnt signaling and FGF receptor-like kinases. (wormbook.org)
  • Protein kinases constitute one of the largest and most important of protein families, accounting for ~2% of genes in a variety of eukaryotic genomes. (wormbook.org)
  • We identified 438 protein kinase genes, including 20 atypical kinases, and an additional 25 kinase fragments or pseudogenes. (wormbook.org)
  • This domain occurred 466 times on human genes ( 1173 proteins). (umbc.edu)
  • Supervised analysis of kinase genes revealed a high-level FLT3 expression in a subset of cases without molecular rearrangements. (aacrjournals.org)
Highly conserved1
  • Many of these pathways are highly conserved, and 53 distinct kinase functions and subfamilies appear to have been conserved between yeasts, nematodes, insects and vertebrates, with a further 91 subfamilies of kinases being seen throughout metazoan genomes. (wormbook.org)
Gene9
  • In response to mechanical stress, VEGF gene and protein expression increased in patient AVM endothelial cells. (researchgate.net)
  • Bevacizumab inhibited circular network formation of endothelial AVM cells and lowered VEGF gene and protein expression, even though the cells were exposed to mechanical stress. (researchgate.net)
  • Protein kinases are one of the largest and most influential of gene families: constituting some 2% of the proteome, they regulate almost all biochemical pathways and may phosphorylate up to 30% of the proteome. (wormbook.org)
  • The duality of this product lies in it's dual specificity to the gene, pH or protein. (reageno.com)
  • Description of the protein which includes the UniProt Function and the NCBI Gene Summary. (nih.gov)
  • C-met is a protein encoded by a met gene in humans, which has tyrosine kinase activity. (cancer-research-network.com)
  • The MAP2K1 gene provides instructions for making a protein known as MEK1 protein kinase. (medlineplus.gov)
  • The identified MAP2K1 gene mutation is a germline mutation that replaces the amino acid glutamic acid with the amino acid glycine at position 102 (written as Glu102Gly or E102G) in MEK1 protein kinase. (medlineplus.gov)
  • Programmable DNA binding proteins have emerged as an exciting platform for engineering synthetic transcription factors for modulating endogenous gene expression 5 - 11 . (cdc.gov)
MEK14
  • Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2. (reactome.org)
  • MEK1 protein kinase appears to be essential for normal development before birth and for survival after birth. (medlineplus.gov)
  • Each mutation changes a single protein building block (amino acid) in MEK1 protein kinase. (medlineplus.gov)
  • The known mutations change single amino acids in MEK1 protein kinase. (medlineplus.gov)
DYRK1A2
  • Other common examples include: ADK1 (Arabidopsis dual specificity kinase 1) CLK1, CLK2, CLK3, CLK4 DSTYK DYRK1A, DYRK1B, DYRK2, DYRK3, DYRK4 Mps1p TESK1, TESK2 TTK The systematic name of this enzyme class is ATP:protein phosphotransferase (Ser/Thr- and Tyr-phosphorylating). (wikipedia.org)
  • We determined the crystal structures of HIPK3 and DYRK1A bound to abemaciclib, showing a similar binding mode to the hinge region of the kinase as observed for Cdk6. (nature.com)
Substrate2
  • 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)
  • By phosphorylating substrate proteins, kinases modify the activity, location and affinities of up to 30% of all cellular proteins, and direct most cellular processes, particularly in signal transduction and co-ordination of complex pathways. (wormbook.org)
Receptor tyrosi1
Cyclin-depend2
Pathways3
  • Cancer cells survive by co-opting intracellular growth pathways regulated through kinase signaling. (escholarship.org)
  • MEKs, involved in MAP pathways, are principal examples of dual-specificity kinases. (wikipedia.org)
  • Some of the new approaches depend on tumor biology and aim specifically to inhibit tumor growth and metastasis by targeting the tumor microenvironment or vasculature (leaving normal cells unaffected) or focusing on specific protein or signal transduction pathways. (medscape.com)
Intracellular3
  • Receptor tyr kinases (RTKs) are integral membrane proteins which contain an extracellular ligand-binding region, a transmembrane segment, and an intracellular tyr kinase domain. (unl.edu)
  • Non-receptor (or cytoplasmic) tyr kinases are distributed in different intracellular compartments and are usually multi-domain proteins containing a catalytic tyr kinase domain as well as various regulatory domains such as SH3 and SH2. (unl.edu)
  • The ubiquitin-proteasome-system (UPS) is responsible for most of the intracellular protein degradation in eukaryotes. (cancer-research-network.com)
Arabidopsis2
  • SIMKK function was further studied in Arabidopsis plants overexpressing SIMKK-yellow fluorescent protein (YFP) fusions. (edu.sa)
  • SIMKK-YFP plants showed enhanced activation of Arabidopsis MPK3 and MPK6 kinases upon salt treatment and exhibited high sensitivity against salt stress at the seedling stage, although they were salt insensitive during seed germination. (edu.sa)
Inactivate2
  • The PPS1 protein was expressed in Escherichia coli, and the protein was shown to catalyze the hydrolysis of p-nitrophenyl phosphate, dephosphorylate phosphotyrosyl, and phosphothreonyl residues in synthetic diphosphorylated peptides and to inactivate the human ERK1 protein. (embl.de)
  • DUSP-MKPs dephosphorylate and inactivate the MAPKs extracellular signal-regulated kinase (ERK), JNK/SAPK, and p38 on tyrosine and threonine residues. (cancer-research-network.com)
Evolutionarily1
  • Homeodomain-interacting protein kinases (HIPKs) are an evolutionarily conserved kinase family comprising the members HIPK1, HIPK2, and HIPK3 in vertebrates, and, additionally, HIPK4 in mammals. (nature.com)
Phosphorylation-regulated1
  • Homeodomain-interacting protein kinases (HIPKs) belong to the CMGC kinase family and are closely related to dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs). (nature.com)
Inhibitor2
  • Dr. Gray's research has had broad impact in the areas of kinase inhibitor design and in circumventing drug resistance. (stanford.edu)
  • Dr. Gray has also developed structure-based, generalized approaches for designing drugs to overcome one of the most common mechanisms of resistance observed against most kinase inhibitor drugs, mutation of the so-called 'gatekeeper' residue, which has been observed in resistance to drugs targeting BCR-ABL, c-KIT and PDGFR. (stanford.edu)
Glycogen2
  • Our results suggest that the combined use of Roscovitine and Kenpaullone may be useful for identifying substrates and physiological roles of cyclin-dependent protein kinases, whereas the combined use of Kenpaullone and LiCl may be useful for identifying substrates and physiological roles of glycogen synthase kinase 3. (nih.gov)
  • Mechanistic investigations revealed reduce GR-Ser211 phosphorylation following PP1α silencing and provide the first indication of the involvement of glycogen synthase kinase 3 (GSK-3). (pp1a.com)
Transmembrane receptor1
  • The HER (erbB) family of transmembrane receptor tyrosine kinases is one of the cytostatic targets in tumor cell growth and survival. (medscape.com)
PTKs3
  • Two kinase families, phosphoinositide-3-kinases (PI3Ks) and protein tyrosine kinases (PTKs), are activated by mutations and amplifications in a disproportionate number of human cancers. (escholarship.org)
  • A subset of these compounds potently, and sometimes selectively, inhibit the mammalian target of rapamycin (mTOR), a Ser/Thr kinase in the PI3K family, placing mTOR in kinase space at the intersection of PI3Ks and PTKs. (escholarship.org)
  • PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. (unl.edu)
Subfamily1
  • Tyrosine-specific kinase subfamily. (unl.edu)
Receptors1
  • In addition, the presence of EVs reduced inflammatory responses in Pam 3 CSK 4 -treated endothelial cells and HEK Dual reporter cells, demonstrating that TLR2-EVs can act as decoy receptors. (frontiersin.org)
Proto-oncogene1
  • The BRAF kinase is a proto-oncogene that activates the MAP kinase pathway, and its mutations are extremely widespread and are mostly seen in nearly 66% of melanomas (Kudchadkar et al. (springeropen.com)
MAPK13
  • Phosphorylation of MAPK1 activates its kinase activity. (reactome.org)
  • DUSP26 inactivates MAPK1 and MAPK3 which leads to dephosphorylation of heat shock factor protein 4 and a decrease in its DNA-binding activity. (prospecbio.com)
  • Necessary for the normal dephosphorylation of the long-lasting phosphorylated forms of spinal MAPK1/3 and MAP kinase p38 induced by peripheral surgery, which drives the resolution of acute postoperative allodynia (By similarity). (nih.gov)
Residues1
Metabolism1
  • Salt-inducible kinase 3 (SIK3) plays a crucial role in various aspects of metabolism. (elifesciences.org)
Biochemistry1
  • His research utilizes the tools of synthetic chemistry, protein biochemistry, and cancer biology to discover and validate new strategies for the inhibition of anti-cancer targets. (stanford.edu)
Sequence similarity3
  • The AGC (cAMP-dependent, cGMP-dependent and protein kinase C) protein kinase family embraces a collection of protein kinases that display a high degree of sequence similarity within their respective kinase domains. (embl.de)
  • The remaining atypical protein kinases (aPK) belong to several families, some of which have structural, but not sequence similarity to ePKs. (wormbook.org)
  • The classification is based on sequence similarity within the kinase domain, the presence of additional domains, known biological functions, and conservation across divergent genomes. (wormbook.org)
Interactions1
  • Protein phosphorylation can regulate enzyme function, mediate protein-protein interactions, alter subcellular localization, and control protein stability. (rupress.org)
Endoplasmic reticulum2
  • Malectin is a membrane-anchored protein of the endoplasmic reticulum that recognises and binds Glc2-N-glycan. (unl.edu)
  • These proteins included catalase, peroxiredoxin, glutathione S-transferase, nucleoside diphosphate kinase 1, endoplasmic reticulum luminal-binding protein 2, and finally plasma membrane aquaporins. (edu.sa)
Vitro2
  • Description: In vitro inhibitory activity using the proprietary LanthaScreen Eu kinase binding assay. (guidetomalariapharmacology.org)
  • Thus, the principle of protein or peptide haptenation could be used in in vitro assays to predict the sensitization potential of a new chemical entity. (cdc.gov)
Kinome2
  • Kinases are deeply conserved in evolution, and the worm has family homologs for over 80% of the human kinome. (wormbook.org)
  • This chapter will introduce the diversity of kinases in C. elegans , and compare them to those of fungi and other metazoans, as well as to preliminary results from analysis of the C. briggsae kinome. (wormbook.org)
Play important roles1
  • Previous reports have suggested that protein kinases play important roles in the regulation of circadian clocks ( Reischl and Kramer, 2011 ). (elifesciences.org)