MAP Kinase Kinase Kinases: Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).MAP Kinase Kinase Kinase 4: A 180-kDa MAP kinase kinase kinase with specificity for MAP KINASE KINASE 4 and MAP KINASE KINASE 6.Mitogen-Activated Protein Kinase Kinases: A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.MAP Kinase Kinase Kinase 1: A 195-kDa MAP kinase kinase kinase with broad specificity for MAP KINASE KINASES. It is found localized in the CYTOSKELETON and can activate a variety of MAP kinase-dependent pathways.MAP Kinase Signaling System: An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Calcium-Calmodulin-Dependent Protein Kinases: A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)MAP Kinase Kinase Kinase 2: A 70-kDa MAP kinase kinase kinase with specificity for MAP KINASE KINASE 5. It is activated during the cellular response to GROWTH FACTORS, oxidative stress, and hyperosmotic conditions.MAP Kinase Kinase Kinase 3: A 70-kDa MAPK kinase kinase with specificity for MAP KINASE KINASE 5.Mitogen-Activated Protein Kinases: A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).MAP Kinase Kinase Kinase 5: A 150-kDa MAP kinase kinase kinase that may play a role in the induction of APOPTOSIS. It has specificity for MAP KINASE KINASE 3; MAP KINASE KINASE 4; and MAP KINASE KINASE 6.MAP Kinase Kinase 1: An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.MAP Kinase Kinase 6: A mitogen-activated protein kinase kinase with specificity for P38 MITOGEN-ACTIVATED PROTEIN KINASES.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.JNK Mitogen-Activated Protein Kinases: A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.MAP Kinase Kinase 3: A mitogen-activated protein kinase kinase with specificity for a subset of P38 MITOGEN-ACTIVATED PROTEIN KINASES that includes MITOGEN-ACTIVATED PROTEIN KINASE 12; MITOGEN-ACTIVATED PROTEIN KINASE 13; and MITOGEN-ACTIVATED PROTEIN KINASE 14.MAP Kinase Kinase 4: A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.MAP Kinase Kinase 7: A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to CYTOKINES.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Phosphatidylinositol 3-Kinases: Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.Proto-Oncogene Proteins c-raf: A ubiquitously expressed raf kinase subclass that plays an important role in SIGNAL TRANSDUCTION. The c-raf Kinases are MAP kinase kinase kinases that have specificity for MAP KINASE KINASE 1 and MAP KINASE KINASE 2.p38 Mitogen-Activated Protein Kinases: A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.MAP Kinase Kinase 2: A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.Mitogen-Activated Protein Kinase 1: A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Mitogen-Activated Protein Kinase 3: A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.Protein Kinase C: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.src-Family Kinases: A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.Calcium-Calmodulin-Dependent Protein Kinase Kinase: A regulatory calcium-calmodulin-dependent protein kinase that specifically phosphorylates CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE TYPE 1; CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE TYPE 2; CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE TYPE 4; and PROTEIN KINASE B. It is a monomeric enzyme that is encoded by at least two different genes.Flavonoids: A group of phenyl benzopyrans named for having structures like FLAVONES.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Cyclic AMP-Dependent Protein Kinases: A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Butadienes: Four carbon unsaturated hydrocarbons containing two double bonds.Ribosomal Protein S6 Kinases: A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Extracellular Signal-Regulated MAP Kinases: A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.p21-Activated Kinases: A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Sensitivity and Specificity: Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)Body Surface Potential Mapping: Recording of regional electrophysiological information by analysis of surface potentials to give a complete picture of the effects of the currents from the heart on the body surface. It has been applied to the diagnosis of old inferior myocardial infarction, localization of the bypass pathway in Wolff-Parkinson-White syndrome, recognition of ventricular hypertrophy, estimation of the size of a myocardial infarct, and the effects of different interventions designed to reduce infarct size. The limiting factor at present is the complexity of the recording and analysis, which requires 100 or more electrodes, sophisticated instrumentation, and dedicated personnel. (Braunwald, Heart Disease, 4th ed)Brain Mapping: Imaging techniques used to colocalize sites of brain functions or physiological activity with brain structures.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.I-kappa B Kinase: A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.CDC2 Protein Kinase: Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Heart Conduction System: An impulse-conducting system composed of modified cardiac muscle, having the power of spontaneous rhythmicity and conduction more highly developed than the rest of the heart.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.3T3 Cells: Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Kinetics: The rate dynamics in chemical or physical systems.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Creatine Kinase: A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.Nitriles: Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Casein Kinase II: A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.Casein Kinases: A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Electrophysiologic Techniques, Cardiac: Methods to induce and measure electrical activities at specific sites in the heart to diagnose and treat problems with the heart's electrical system.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.eIF-2 Kinase: A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.Precipitin Tests: Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Adaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesPyruvate Kinase: ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.NF-kappa B: Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.MAP Kinase Kinase 5: A mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 7.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.Proto-Oncogene Proteins c-akt: A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.Phosphotransferases (Alcohol Group Acceptor): A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.Glycogen Synthase Kinase 3: A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.PhosphoproteinsThymidine Kinase: An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21.Imidazoles: Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Cell Line, Tumor: A cell line derived from cultured tumor cells.AMP-Activated Protein Kinases: Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Osmotic Pressure: The pressure required to prevent the passage of solvent through a semipermeable membrane that separates a pure solvent from a solution of the solvent and solute or that separates different concentrations of a solution. It is proportional to the osmolality of the solution.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Echo-Planar Imaging: A type of MAGNETIC RESONANCE IMAGING that uses only one nuclear spin excitation per image and therefore can obtain images in a fraction of a second rather than the minutes required in traditional MRI techniques. It is used in a variety of medical and scientific applications.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.rho-Associated Kinases: A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)1-Phosphatidylinositol 4-Kinase: An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.CDC2-CDC28 Kinases: A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Transcription Factor AP-1: A multiprotein complex composed of the products of c-jun and c-fos proto-oncogenes. These proteins must dimerize in order to bind to the AP-1 recognition site, also known as the TPA-responsive element (TRE). AP-1 controls both basal and inducible transcription of several genes.Phosphoprotein Phosphatases: A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.ChromonesAurora Kinases: A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.Protein Kinase C-delta: A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)Phosphothreonine: The phosphoric acid ester of threonine. Used as an identifier in the analysis of peptides, proteins, and enzymes.Protein Kinase C-alpha: A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.Saccharomyces cerevisiae Proteins: Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.Ribosomal Protein S6 Kinases, 90-kDa: A family of ribosomal protein S6 kinases that are structurally distinguished from RIBOSOMAL PROTEIN S6 KINASES, 70-KDA by their apparent molecular size and the fact they contain two functional kinase domains. Although considered RIBOSOMAL PROTEIN S6 KINASES, members of this family are activated via the MAP KINASE SIGNALING SYSTEM and have been shown to act on a diverse array of substrates that are involved in cellular regulation such as RIBOSOMAL PROTEIN S6 and CAMP RESPONSE ELEMENT-BINDING PROTEIN.Androstadienes: Derivatives of the steroid androstane having two double bonds at any site in any of the rings.Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes (GENES, MOS). They function in the cell cycle to maintain MATURATION PROMOTING FACTOR in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time.PC12 Cells: A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.MorpholinesProteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.ras Proteins: Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein (ONCOGENE PROTEIN P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). This enzyme was formerly listed as EC 3.6.1.47.Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.Mitogen-Activated Protein Kinase 8: A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Image Processing, Computer-Assisted: A technique of inputting two-dimensional images into a computer and then enhancing or analyzing the imagery into a form that is more useful to the human observer.Diacylglycerol Kinase: An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Oncogene Proteins v-mos: Transforming proteins coded by mos oncogenes. The v-mos proteins were originally isolated from the Moloney murine sarcoma virus (Mo-MSV).Naphthalimides: Compounds with three fused rings that appear like a naphthalene fused to piperidone or like a benz(de)isoquinoline-1,3-dione (not to be confused with BENZYLISOQUINOLINES which have a methyl separating the naphthyl from the benzyl rings). Members are CYTOTOXINS.Cell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.Focal Adhesion Kinase 1: A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Focal Adhesion Protein-Tyrosine Kinases: A family of non-receptor, PROLINE-rich protein-tyrosine kinases.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Epidermal Growth Factor: A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.Heart Atria: The chambers of the heart, to which the BLOOD returns from the circulation.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Proto-Oncogene Proteins p21(ras): Cellular proteins encoded by the H-ras, K-ras and N-ras genes. The proteins have GTPase activity and are involved in signal transduction as monomeric GTP-binding proteins. Elevated levels of p21 c-ras have been associated with neoplasia. This enzyme was formerly listed as EC 3.6.1.47.Fungal Proteins: Proteins found in any species of fungus.Myosin-Light-Chain Kinase: An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Calcium-Calmodulin-Dependent Protein Kinase Type 2: A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.Janus Kinase 2: A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Two-Hybrid System Techniques: Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Phosphoserine: The phosphoric acid ester of serine.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.raf Kinases: A family of closely-related serine-threonine kinases that were originally identified as the cellular homologs of the retrovirus-derived V-RAF KINASES. They are MAP kinase kinase kinases that play important roles in SIGNAL TRANSDUCTION.Catheter Ablation: Removal of tissue with electrical current delivered via electrodes positioned at the distal end of a catheter. Energy sources are commonly direct current (DC-shock) or alternating current at radiofrequencies (usually 750 kHz). The technique is used most often to ablate the AV junction and/or accessory pathways in order to interrupt AV conduction and produce AV block in the treatment of various tachyarrhythmias.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Mice, Inbred C57BLProtein Kinase C-epsilon: A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.Mitogen-Activated Protein Kinase 7: A 110-kDa extracellular signal-regulated MAP kinase that is activated in response to cellular stress and by GROWTH FACTOR RECEPTORS-mediated pathways.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Calcium-Calmodulin-Dependent Protein Kinase Type 1: A monomeric calcium-calmodulin-dependent protein kinase subtype that is expressed in a broad variety of mammalian cell types. Its expression is regulated by the action of CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE. Several isoforms of this enzyme subtype are encoded by distinct genes.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).TOR Serine-Threonine Kinases: A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Pericardium: A conical fibro-serous sac surrounding the HEART and the roots of the great vessels (AORTA; VENAE CAVAE; PULMONARY ARTERY). Pericardium consists of two sacs: the outer fibrous pericardium and the inner serous pericardium. The latter consists of an outer parietal layer facing the fibrous pericardium, and an inner visceral layer (epicardium) resting next to the heart, and a pericardial cavity between these two layers.Transcriptional Activation: Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.Protein Kinase C beta: PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.Cyclin-Dependent Kinase 2: A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Cyclic GMP-Dependent Protein Kinases: A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Tachycardia, Ventricular: An abnormally rapid ventricular rhythm usually in excess of 150 beats per minute. It is generated within the ventricle below the BUNDLE OF HIS, either as autonomic impulse formation or reentrant impulse conduction. Depending on the etiology, onset of ventricular tachycardia can be paroxysmal (sudden) or nonparoxysmal, its wide QRS complexes can be uniform or polymorphic, and the ventricular beating may be independent of the atrial beating (AV dissociation).Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Genes, Reporter: Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.Indoles: Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Focal Adhesion Kinase 2: A non-receptor protein-tyrosine kinase that is expressed primarily in the BRAIN; OSTEOBLASTS; and LYMPHOID CELLS. In the CENTRAL NERVOUS SYSTEM focal adhesion kinase 2 modulates ION CHANNEL function and MITOGEN-ACTIVATED PROTEIN KINASES activity.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Cyclin-Dependent Kinase 5: A serine-threonine kinase that plays important roles in CELL DIFFERENTIATION; CELL MIGRATION; and CELL DEATH of NERVE CELLS. It is closely related to other CYCLIN-DEPENDENT KINASES but does not seem to participate in CELL CYCLE regulation.Reproducibility of Results: The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results.Phosphotyrosine: An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Dual Specificity Phosphatase 1: A dual specificity phosphatase subtype that plays a role in intracellular signal transduction by inactivating MITOGEN-ACTIVATED PROTEIN KINASES. It has specificity for P38 MITOGEN-ACTIVATED PROTEIN KINASES and JNK MITOGEN-ACTIVATED PROTEIN KINASES.Phosphoglycerate Kinase: An enzyme catalyzing the transfer of a phosphate group from 3-phospho-D-glycerate in the presence of ATP to yield 3-phospho-D-glyceroyl phosphate and ADP. EC 2.7.2.3.Electrophysiology: The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.Mitogen-Activated Protein Kinase 14: A 38-kDa mitogen-activated protein kinase that is abundantly expressed in a broad variety of cell types. It is involved in the regulation of cellular stress responses as well as the control of proliferation and survival of many cell types. The kinase activity of the enzyme is inhibited by the pyridinyl-imidazole compound SB 203580.Peptide Mapping: Analysis of PEPTIDES that are generated from the digestion or fragmentation of a protein or mixture of PROTEINS, by ELECTROPHORESIS; CHROMATOGRAPHY; or MASS SPECTROMETRY. The resulting peptide fingerprints are analyzed for a variety of purposes including the identification of the proteins in a sample, GENETIC POLYMORPHISMS, patterns of gene expression, and patterns diagnostic for diseases.Mitogen-Activated Protein Kinase 9: A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 48 and 54 KD exist due to multiple ALTERNATIVE SPLICING.Phosphorylase Kinase: An enzyme that catalyzes the conversion of ATP and PHOSPHORYLASE B to ADP and PHOSPHORYLASE A.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases ... "Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases". ... "Extracellular signal-regulated kinases phosphorylate mitogen-activated protein kinase phosphatase 3/DUSP6 at serines 159 and ... a dual specificity MAP kinase phosphatase, in pancreatic cancer". Cytogenetics and Cell Genetics. 82 (3-4): 156-9. doi:10.1159/ ...
"Entrez Gene: STK38 serine/threonine kinase 38". Tripodis N, Mason R, Humphray SJ, et al. (1999). "Physical map of human 6p21.2- ... 2004). "Structure of the Ca2+/S100B/NDR kinase peptide complex: insights into S100 target specificity and activation of the ... Serine/threonine-protein kinase 38 is an enzyme that in humans is encoded by the STK38 gene. GRCh38: Ensembl release 89: ... Bichsel SJ, Tamaskovic R, Stegert MR, Hemmings BA (2005). "Mechanism of activation of NDR (nuclear Dbf2-related) protein kinase ...
... for ERK2/p38alpha and JNK map kinases mediate catalytic activation and substrate selectivity of map kinase phosphatase-1". J. ... "Identification of a docking groove on ERK and p38 MAP kinases that regulates the specificity of docking interactions". EMBO J. ... "Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2". EMBO J. 16 (8): 1909-20. doi:10.1093/ ... The activation of this kinase requires its phosphorylation by upstream kinases. Upon activation, this kinase translocates to ...
"Biochemical characterization and localization of the dual specificity kinase CLK1". J. Cell Sci. 113. ( Pt 18): 3241-53. PMID ... Chen CS, Bejcek BE, Kersey JH (1995). "A mapping study of 13 genes on human chromosome bands 4q11→q25". Cytogenet. Cell Genet. ... 2000). "Characterization of human HtrA2, a novel serine protease involved in the mammalian cellular stress response". Eur. J. ... 2001). "Creation of genome-wide protein expression libraries using random activation of gene expression". Nat. Biotechnol. 19 ( ...
"A mammalian scaffold complex that selectively mediates MAP kinase activation". Science. 281 (5383): 1671-4. doi:10.1126/science ... Hu MC, Qiu WR, Wang YP (Nov 1997). "JNK1, JNK2 and JNK3 are p53 N-terminal serine 34 kinases". Oncogene. 15 (19): 2277-87. doi: ... "JNK2 contains a specificity-determining region responsible for efficient c-Jun binding and phosphorylation". Genes & ... The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple ...
"Novel homologues of CSBP/p38 MAP kinase: activation, substrate specificity and sensitivity to inhibition by pyridinyl ... "Serine/Threonine kinases 3pK and MAPK-activated protein kinase 2 interact with the basic helix-loop-helix transcription factor ... This kinase functions as a mitogen-activated protein kinase (MAP kinase)- activated protein kinase. MAP kinases are also known ... MAP) kinase-activated protein kinase-3, a novel substrate of CSBP p38 MAP kinase". J Biol Chem. 271 (14): 8488-92. doi:10.1074/ ...
MAP kinase signaling specificity". Science. 296 (5577): 2345-7. doi:10.1126/science.1073344. PMID 12089430. Roskoski R (August ... Chadee DN, Yuasa T, Kyriakis JM (2002). "Direct activation of mitogen-activated protein kinase kinase kinase MEKK1 by the ... RAF kinases are a family of three serine/threonine-specific protein kinases that are related to retroviral oncogenes. The mouse ... Activation of RAF kinases requires interaction with RAS-GTPases. The three RAF kinase family members are: A-RAF B-RAF c-Raf ...
Similarly, both dual-specificity MAP kinase phosphatases and MAP-specific tyrosine phosphatases bind to MAP kinases through the ... A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids serine ... This is conducted by specialized enzymes of the STE protein kinase group. In the case of classical MAP kinases, the activation ... Signal transduction MAP kinase kinase MAP kinase kinase kinase MAP kinase kinase kinase kinase MAPK1 (ERK2) MAPK3 (ERK1) MAPK7 ...
Each of these mutations maps to the kinase domain of DBT gene. The short- and long-period alleles of DBT enhance or attenuate, ... The CK1 family of monomeric serine-threonine protein kinases is found in eukaryotic organisms from yeast to humans. Mammals ... Phosphorylation of LRP6 by CK1gamma promotes binding of axin to LRP and activation of the Wnt signaling pathway. CK1ε and CK1δ ... The family members appear to have similar substrate specificity in vitro, and substrate selection is thought to be regulated in ...
... which is involved in the MAP kinase cascade, is a mixed serine/threonine and tyrosine kinase and, hence a dual-specificity ... Autophosphorylation of the activation loop causes the two subdomains of the intrinsic kinase to shift, opening the kinase ... Most kinases act on both serine and threonine (serine/threonine kinases), others act on tyrosine (tyrosine kinases), and a ... While MAP kinases are serine/threonine-specific, they are activated by combined phosphorylation on serine/threonine and ...
The activation requires its phosphorylation by MAP kinase kinases (MKKs), or its autophosphorylation triggered by the ... "Identification of a docking groove on ERK and p38 MAP kinases that regulates the specificity of docking interactions". The EMBO ... p38 MAPKs are also known as stress-activated serine/threonine-specific kinases (SAPKs). In addition to MAPK14 for p38α MAPK, ... The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple ...
These events promote many signaling cascades (such as the MAP kinase pathway) that generate responses like chemotaxis, ... Activation of G proteins, by chemokine receptors, causes the subsequent activation of an enzyme known as phospholipase C (PLC ... and an intracellular C-terminus containing serine and threonine residues important for receptor regulation. The first two ... while the N-terminal domain of the chemokine receptor determines ligand binding specificity. Chemokine receptors associate with ...
... for ERK2/p38alpha and JNK map kinases mediate catalytic activation and substrate selectivity of map kinase phosphatase-1". J. ... 2001). „Identification of a docking groove on ERK and p38 MAP kinases that regulates the specificity of docking interactions". ... 1997). „Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2". EMBO J. ENGLAND. 16 (8): 1909- ... Gupta, S; Davis R J (1994). „MAP kinase binds to the NH2-terminal activation domain of c-Myc". FEBS Lett. NETHERLANDS. 353 (3 ...
The acetylation occurs in the C-terminal half of the PRD domain and is required for ATM kinase activation and for its ... "Substrate specificities and identification of putative substrates of ATM kinase family members". J. Biol. Chem. 274 (53): 37538 ... mapping the region of interaction". Nat. Genet. 20 (4): 398-400. doi:10.1038/3882. PMID 9843217. Westphal CH, Schmaltz C, Rowan ... ATM serine/threonine kinase, symbol ATM, is a serine/threonine protein kinase that is recruited and activated by DNA double- ...
The initiated MAP kinase pathway activates specific cellular mechanisms involved in chemotaxis, degranulation, release of ... The N-terminal end of a chemokine receptor binds to chemokine(s) and is important for ligand specificity. G-proteins couple to ... Inflammatory chemokines are expressed upon leukocyte activation, whereas homeostatic chemokines show continual expression. ... which phosphorylates serine and threonine residues in the tail of the chemokine receptor, causing its desensitisation or ...
IL-17F utilizes IL-17RA and IL-17RC as its receptors, and activates the MAP kinase related pathway. IL-17F is derived from ... Instead, a serine replaces the cysteine at this position. This unique feature is conserved in the other IL-17 family members. ... New immature DCs are also recruited by CCL20 via chemotaxis where their activation restarts and amplifies the cycle of ... that present with individual ligand specificities. Within this family of receptors, IL-17RA is the best-described. IL-17RA ...
Full activation of AKT occurs upon phosphorylation of serine 473 by the TORC2 complex of the mTOR protein kinase. The "PI3-k/ ... They observed unique substrate specificity and chromatographic properties of the products of the lipid kinase, leading to the ... "A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling". Cell. 125 (4): 733-47. doi: ... Many of the PI 3-kinases appear to have a serine/threonine kinase activity in vitro; however, it is unclear whether this has ...
Activins signal through a heteromeric complex of receptor serine kinases which include at least two type I (I and IB) and two ... and a cytoplasmic domain with predicted serine/threonine specificity. Type I receptors are essential for signaling; and type II ... Ishikawa S, Kai M, Murata Y, Tamari M, Daigo Y, Murano T, Ogawa M, Nakamura Y (July 1998). "Genomic organization and mapping of ... Macías-Silva M, Hoodless PA, Tang SJ, Buchwald M, Wrana JL (1998). "Specific activation of Smad1 signaling pathways by the BMP7 ...
Dual specificity mitogen-activated protein kinase kinase 7, also known as MAP kinase kinase 7 or MKK7, is an enzyme that in ... "Activation of stress-activated protein kinases/c-Jun N-terminal protein kinases (SAPKs/JNKs) by a novel mitogen-activated ... The MKKKs relate to MKK7 through its DVD site at the C-terminus and phosphorylate MKK7 at serine and threonine residues. Once ... Stress-activated protein kinase kinase 4 (SAPK kinase 4, SAPKK4) c-Jun N-terminal kinase kinase 2 (JNK kinase 2, JNKK2) Stress- ...
Dual specificity mitogen-activated protein kinase kinase 6 also known as MAP kinase kinase 6 (MAPKK 6) or MAPK/ERK kinase 6 is ... protein kinase binding. • protein serine/threonine kinase activity. • identical protein binding. • MAP kinase kinase activity. ... "Human mitogen-activated protein kinase kinase kinase mediates the stress-induced activation of mitogen-activated protein kinase ... MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for ...
... for ERK2/p38alpha and JNK map kinases mediate catalytic activation and substrate selectivity of map kinase phosphatase-1». J. ... de 2001). «Identification of a docking groove on ERK and p38 MAP kinases that regulates the specificity of docking interactions ... de 2000). «Characterization of a novel human serine protease that has extensive homology to bacterial heat shock endoprotease ... de 2001). «p38 Kinase-dependent MAPKAPK-2 activation functions as 3-phosphoinositide-dependent kinase-2 for Akt in human ...
... gene encodes a serine/threonine kinase that controls initiation of mitosis. NIMA-related kinases (NEKs) are a group of protein ... Kobayashi T, Cohen P (1999). "Activation of serum- and glucocorticoid-regulated protein kinase by agonists that activate ... "Molecular basis for the substrate specificity of NIMA-related kinase-6 (NEK6). Evidence that NEK6 does not phosphorylate the ... 3→q34.11 by radiation hybrid mapping". Cytogenet Cell Genet. 87 (3-4): 271-2. doi:10.1159/000015445. PMID 10702691. "Entrez ...
... of Pyst2 as a cytosolic dual-specificity MAP kinase phosphatase and its catalytic activation by both MAP and SAP kinases". J. ... DUSPs are characterized by their ability to de-phosphorylate both tyrosine (EC 3.1.3.48) and serine / threonine (EC 3.1.3.16) ... of Pyst2 as a cytosolic dual-specificity MAP kinase phosphatase and its catalytic activation by both MAP and SAP kinases". J. ... 1996). "Differential regulation of the MAP, SAP and RK/p38 kinases by Pyst1, a novel cytosolic dual-specificity phosphatase". ...
"The structural basis for the specificity of pyridinylimidazole inhibitors of p38 MAP kinase". Chem. Biol. 4 (6): 423-31. doi: ... Muller S, Demotz S, Bulliard C, Valitutti S (1999). "Kinetics and extent of protein tyrosine kinase activation in individual T ... By installing phospho-serine, phospho-threonine or analogous phosphonate mimics into native proteins, researchers are able to ... Pargellis C, Ton L, Churchill L, CIrillo PF, Gilmore T, Graham AG, Grob PM, Hickey ER, Moss N (2002). "p38 MAP kinase". Nature ...
The activin molecule modulates the actin dynamics in dendritic spines through the MAP-kinase pathway. By changing the F-actin ... and glycine or D-serine for activation of NMDA receptors. The turning point for the synaptic modification of a synapse has been ... Specificity is also an important aspect of CAMKII signaling involving nanodomain calcium. The spatial gradient of PKA between ... Calcium influx from NMDA receptors is necessary for the activation of CaMKII. This activation is localized to spines with focal ...
Dual specificity mitogen-activated protein kinase kinase 2 is an enzyme that in humans is encoded by the MAP2K2 gene. It is more commonly known as MEK2, but has many alternative names including CFC4, MKK2, MAPKK2 and PRKMK2. The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is known to play a critical role in mitogen growth factor signal transduction. It phosphorylates and thus activates MAPK1/ERK2 and MAPK3/ERK1. The activation of this kinase ...
RAF proto-oncogene serine/threonine-protein kinase, also known as proto-oncogene c-RAF or simply c-Raf or even Raf-1, is an enzyme that in humans is encoded by the RAF1 gene. The c-Raf protein is part of the ERK1/2 pathway as a MAP kinase kinase kinase (MAP3K) that functions downstream of the Ras subfamily of membrane associated GTPases. C-Raf is a member of the Raf kinase family of serine/threonine-specific protein kinases, from the TKL (Tyrosine-kinase-like) group of kinases. The first Raf gene, v-Raf was found in 1983. It was isolated ...
A játékban szereplő helyszínek a Half-Life 2 tengerparton játszódó részéhez kapcsolódtak volna, azonban ezt a fejlesztők elvetették. A történet kezdetén Gordon Freeman egy sziklás tengerparton ébred, ahol egy halász üdvözli őt. A halász megkéri, hogy pusztítsa el a Combine Headcrab-kilövő szerkezetét a sziget templomában. Gordon elindul, pár deszka és gyertyatartó a gépbe helyezésével elpusztítja, ezután pedig kifele menet egy vadászrepülővel találkozik. Ezután a játéknak vége. A halászember az első modell a Half-Life-sorozatban, akit nem valódi emberről mintáztak. Többek között, a halászember meggyilkolása (különféle csalások használatával) a játék összeomlásához vezet.. ...
Obnoviteľné zdroje energie (OZE) sú také zdroje, ktoré sa prirodzene obnovujú v priebehu ich využívania. Ide o energetické toky, ktoré sa prirodzene vyskytujú v blízkosti zemského povrchu, zásoby, ktoré sa obnovujú aspoň tak rýchlo, ako sú spotrebuvávané. V ich čerpaní možno hypoteticky pokračovať ďalšie miliardy rokov - v podstate kým bude svietiť Slnko. Konkrétne ide o slnečné žiarenie a z toho odvodenú veternú energiu a vodnú energiu, ďalej o energiu prílivu, geotermálnu energiu, biomasu atď. Technológie obnoviteľných zdrojov energie slnečnú energiu, a veternú energiu. V roku 2006, približne 18 % celkovej svetovej spotreby energie pochádzalo z obnoviteľných zdrojov energie; 13 % z tradičnej biomasy spôsobmi akým je spaľovanie dreva. Vodná energia bola ďalším najväčším obnoviteľným zdrojom, poskytujúca 3 %, nasledovaná horúcou vodou na vykurovanie ktorá prispela 1,3 %. Moderné technológie, ako geotermálna, veterná, ...
Ak ste sa sem dostali cez odkaz v článku, prosím, vráťte sa a opravte ho tak, aby odkazoval priamo na najvhodnejší význam ...
Do skladby som chcel priniesť niečo, čo je pre nás nové a nie je pre nás typické, tak prečo do nej nezahrnúť Garyho Holta? Je to skvelý gitarista a jeho sólo znie skvele ...
Zaradi pogoste uporabe betalaktamskih zdravil so nekatere bakterije razvile odpornost proti njim. Nekatere bakterije proizvajajo prej omejeni encim betalaktamazo, ki izniči učinek betalaktamskega antibiotika, ker cepi betalaktamski obroč.. Za preprečitev tovrstne odpornosti bakterij so na trgu kombinacije betalaktamskih antibiotikov z zaviralci betalaktamaze. Takšna kombinacija je npr. amoksicilin + klavulanska kislina. Klavulanska kislina je zaviralec betalaktamaze, ker se nepovratno veže na encim in slednji se več ne more vezati na betalaktamsko učinkovino (v tem primeru amoksicilin).. ...
RAF proto-oncogene serine/threonine-protein kinase, also known as proto-oncogene c-RAF or simply c-Raf or even Raf-1, is an enzyme that in humans is encoded by the RAF1 gene. The c-Raf protein is part of the ERK1/2 pathway as a MAP kinase kinase kinase (MAP3K) that functions downstream of the Ras subfamily of membrane associated GTPases. C-Raf is a member of the Raf kinase family of serine/threonine-specific protein kinases, from the TKL (Tyrosine-kinase-like) group of kinases. The first Raf gene, v-Raf was found in 1983. It was isolated ...
Dual specificity mitogen-activated protein kinase kinase 2 is an enzyme that in humans is encoded by the MAP2K2 gene. It is more commonly known as MEK2, but has many alternative names including CFC4, MKK2, MAPKK2 and PRKMK2. The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is known to play a critical role in mitogen growth factor signal transduction. It phosphorylates and thus activates MAPK1/ERK2 and MAPK3/ERK1. The activation of this kinase ...
Mitogen-activated protein kinase 13 (MAPK 13), also known as stress-activated protein kinase 4 (SAPK4), is an enzyme that in humans is encoded by the MAPK13 gene. The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is closely related to p38 MAP kinase, both of which can be activated by proinflammatory cytokines and cellular stress. MAP ...
Dual specificity mitogen-activated protein kinase kinase 4 is an enzyme that in humans is encoded by the MAP2K4 gene. This gene encodes a dual specificity protein kinase that belongs to the Ser/Thr protein kinase family. This kinase is a direct activator of MAP kinases in response to various environmental stresses or mitogenic stimuli. It has been shown to activate MAPK8/JNK1, MAPK9/JNK2, and MAPK14/p38, but not MAPK1/ERK2 or MAPK3/ERK1. This kinase is phosphorylated, and thus activated by ...
Söderström T.S., Poukkula M., Holmström T.H., et al. Mitogen-activated protein kinase/extracellular signal-regulated kinase signaling in activated T cells abrogates TRAIL-induced apoptosis upstream of the mitochondrial amplification loop and caspase-8. (англ.) // J. Immunol. (англ.)русск. : journal. - 2002. - Vol. 169, no. 6. - P. 2851-2860. - PMID 12218097. ...
MAPKK 6 is a member of the dual specificity protein kinase family, which functions as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein phosphorylates and activates p38 MAP kinase in response to inflammatory cytokines or environmental stress. As an essential component of p38 MAP kinase mediated signal transduction pathway, this gene is involved in many cellular processes such as stress-induced cell cycle arrest, ...
MAP kinase/Erk kinases, also named MAPKK) and serine/threonine kinases ERKs (extracellular signal-regulated kinases, also named ... Growth factors induce nuclear translocation of MAP kinases (p42 mapk and p44 mapk) but not of their activator MAP kinase kinase ... Constitutive mutant and putative regulatory serine phosphorylation site on mammalian MAP kinase kinase (MEK-1). EMBO J. 13: ... 3-kinase and PI 4-kinase binding to the CD4-p56lck complex: the p56lck SH3 domain binds to PI 3-kinase but not PI 4-kinase. Mol ...
... are sensed by the membrane receptor kinase BRASSINOSTEROID INSENSITIVE 1 (BRI1). Brassinosteroid binding to the BRI1 leucine- ... rich repeat (LRR) domain induces heteromerisation with a SOMATIC EMBRYOGENESIS RECEPTOR KINASE (SERK)-family co-r … ... Mapping previously identified serine/threonine and tyrosine phosphorylation sites onto the structure, we analyse their ... providing insight into the evolution of dual-specificity kinases in plants. Phosphorylation of Thr1039, Ser1042 and Ser1044 ...
Activation of MAP kinases causes activation of so-called dual specificity phosphatases, dephosphorylating MAP kinases and thus ... MAP kinases, which belong to a large family of serine/threonine kinases, constitute major inflammatory signalling highways from ... MAP kinase kinase; MAPKKK, MAP kinase kinase kinase; MEF, myocyte enhance factor; MEK, MAP/ERK kinase; MKK, MAP kinase kinase; ... MAPK, MAP kinase; MAPKK, MAP kinase kinase; MAPKKK, MAP kinase kinase kinase. ...
... and the dual-specificity kinases, MAP kinase/ERK kinase 1 (MEK 1) and MEK 2 (7). Dual phosphorylation of the TEY motif on ERK ... Requirement for the integration of signals from two distinct phosphorylation pathways for activation of MAP kinase.Nature343 ... are regulated by a cascade of upstream kinases which include the serine/threonine kinase, Raf-1, ... kinase and a MAP kinase kinase in polymorphonuclear leukocytes.Biochem. J.2901993483488. ...
CCKR signaling map, T-cell activation Dual specificity protein kinase which acts as an essential component of the MAP kinase ... Serine/threonine-protein kinase VRK1 Q99986 Non-receptor serine/threonine protein kinase Serine/threonine kinase involved in ... CCKR signaling map Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. ... Negligible PIP5 kinase activity. Binds to ubiquitinated proteins STK25 Serine/threonine-protein kinase 25 O00506 Kinase ...
... or MAPK/ERK kinase 2. The dual specificity kinases MEK1 and MEK2 are activated by RAF and mediate phosphorylation of ERK1 and ... and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. Depending on the cellular ... MEK2 is a serine/threonine kinase also known as MAP kinase kinase (MAPKK 2) ... MEK2 is a serine/threonine kinase also known as MAP kinase kinase (MAPKK 2) or MAPK/ERK kinase 2. The dual specificity kinases ...
This activation is mediated via MAP kinase kinase (p45mapkk), a dual specificity kinase which phosphorylates two key regulatory ... Mitogen-activated protein kinases (p42mapk and p44mapk) are serine/threonine kinases that are activated rapidly in cells ... Growth factors induce nuclear translocation of MAP kinases (p42mapk and p44mapk) but not of their activator MAP kinase kinase ( ... Growth factors induce nuclear translocation of MAP kinases (p42mapk and p44mapk) but not of their activator MAP kinase kinase ( ...
19 antibodies to MKP-1 and validated for use in 6 applications (Immunohistochemistry,Flow Cytometry,Western Blot, ... Furthermore, it suppresses the activation of MAP kinase by oncogenic ras in extracts of Xenopus oocytes. Thus, DUSP1 may play ... Dual specificity protein phosphatase hVH1; DUS1; EC 3.1.3.16; EC 3.1.3.48; MAP kinase phosphatase 1; MAP kinase phosphatase-1; ... serine/threonine specific protein phosphatase ... MAP) kinase in vitro by the concomitant dephosphorylation of ...
To map the phosphorylation site systematically, we decided for a peptide array that displays 73 peptides containing all serine ... OConnell RM, Vaidya SA, Perry AK, Saha SK, Dempsey PW, Cheng G (2005) Immune activation of type I IFNs by Listeria ... Franca R, Belfiore A, Spadari S, Maga G (2007) Human DEAD‐box ATPase DDX3 shows a relaxed nucleoside substrate specificity. ... Kinase activity was then measured by scintillation counting.. For those kinase assays where recombinant proteins were used as ...
A proline/serine/threonine rich region at the C-terminus is necessary for transcriptional activation of target genes and ... Phosphorylated; probably by MAP kinases (MAPK) (By similarity). Isoform 3 is phosphorylated on Ser-340. ... Tissue specificity. Specifically expressed in osteoblasts.. * Involvement in disease. Defects in RUNX2 are the cause of ... alpha 1(I) collagen, LCK, IL-3 and GM-CSF promoters (By similarity). Inhibits MYST4-dependent transcriptional activation. ...
A proline/serine/threonine rich region at the C-terminus is necessary for transcriptional activation of target genes and ... Phosphorylated; probably by MAP kinases (MAPK) (By similarity). Isoform 3 is phosphorylated on Ser-340. ... Tissue specificity. Specifically expressed in osteoblasts.. * Involvement in disease. Defects in RUNX2 are the cause of ... Leptin regulates disc cartilage endplate degeneration and ossification through activation of the MAPK-ERK signalling pathway in ...
The p38 MAP kinases can be activated by osmotic shock. This involves activation of MAP kinase kinase kinases, of which several ... Upon activation, the type I receptors phosphorylate members of the receptor-regulated subfamily of Smads at two serines in an ... We then extended our analysis of the specificity of SB-431542 by testing its effect on transcriptional activation mediated by ... the MAP kinase kinase kinase, Raf, and the MAP kinase kinases MEK1 and MEK2 (Bogdan and Klambt, 2001). We tested the effect of ...
TGF-beta activated kinase 1; Transforming growth factor-beta-activated kinase 1 Matsumoto and his colleagues discovered the ... MAP3K7; MEKK7; Mitogen-activated protein kinase kinase kinase 7; ... TAK1 negatively regulates NF-κB and p38 MAP kinase activation ... MAPKKK is a serine/threonine-specific protein kinase involved in cellular signal transduction, where MAPKKKs phosphorylate ... downstream dual-specificity protein kinase MAPKKs, which in turn phosphorylates the MAPKs to regulate a variety of biological ...
MAP) kinase pathway. The first kinase in the cascade is the serine-threonine kinase Raf, which phosphorylates and activates MAP ... p75LNTR and the Trk family of tyrosine kinases. All NTs bind to p75LNTR. However, they show a high degree of specificity for ... PI 3-kinase is not required for the early activation of the ERK-MAP kinases after NGF stimulation.Another protein that becomes ... Activation of the MAP kinase pathway by the protein kinase raf.Cell 71 1992 335 342 ...
RAF kinases activate the dual specificity kinases MEK1 and MEK2 through phosphorylation at serine 218 and serine 222, ... Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation ... The RAS-RAF-MEK (MAP-ERK kinase)-ERK (extracellular signal-regulated kinase) pathway plays a central role in driving ... The RAS-RAF-MEK (MAP-ERK kinase)-ERK (extracellular signal-regulated kinase) pathway controls cell growth, differentiation, ...
SCP1 phosphatase substrate specificity: CdcA3 could be an enzymatic substrate for SCP1. Title: A study of substrate specificity ... SCP1 regulates c-Myc stability and functions through dephosphorylating c-Myc Serine-62. Title: SCP1 regulates c-Myc stability ... Our results provide a novel mechanistic insight into the activation of Myc by 27-HC via transcriptional repression of PP2A, ... Genes and mapped phenotypes. Search database. All Databases. Assembly. Biocollections. BioProject. BioSample. BioSystems. Books ...
... consisting of a MAP kinase kinase kinase (MAPKKK or MAP3K), a MAP kinase kinase (MAPKK or MAP2K), and a MAP kinase (MAPK). ... Mitogen-activated protein kinases (MAPKs) are a widely conserved family of serine/threonine protein kinases involved in many ... Specificity / Sensitivity Each antibody in the Phospho-Erk1/2 Pathway Sampler Kit recognizes only the phosphorylated form of ... MEK1 and MEK2 activate p44 and p42 through phosphorylation of activation loop residues Thr202/Tyr204 and Thr185/Tyr187, ...
Mitogen-activated protein kinase (MAPK) cascades are key signaling pathways involved in the regulation of normal cell ... MAP Kinase Kinase Kinases / antagonists & inhibitors* * MAP Kinase Kinase Kinases / physiology * MAP Kinase Signaling System / ... ERK activation also promotes upregulated expression of EGFR ligands, promoting an autocrine growth loop critical for tumor ... is a downstream component of an evolutionarily conserved signaling module that is activated by the Raf serine/threonine kinases ...
... consisting of a MAP kinase kinase kinase (MAPKKK or MAP3K), a MAP kinase kinase (MAPKK or MAP2K), and a MAP kinase (MAPK). ... Mitogen-activated protein kinases (MAPKs) are a widely conserved family of serine/threonine protein kinases involved in many ... Specificity / Sensitivity. Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204) (197G2) Rabbit mAb (Alexa Fluor® 488 Conjugate) detects ... MEK1 and MEK2 activate p44 and p42 through phosphorylation of activation loop residues Thr202/Tyr204 and Thr185/Tyr187, ...
Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases ... "Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases". ... "Extracellular signal-regulated kinases phosphorylate mitogen-activated protein kinase phosphatase 3/DUSP6 at serines 159 and ... a dual specificity MAP kinase phosphatase, in pancreatic cancer". Cytogenetics and Cell Genetics. 82 (3-4): 156-9. doi:10.1159/ ...
... hormones and neurotransmitters is mediated through two closely related MAP kinases, p44 and p42, designated extracellular- ... The activation of signal transduction pathways by growth factors, ... In response to activation, MAP kinases phosphorylate downstream components on serine and threonine. Upstream MAP kinase ... Specificity. Specificity:. p-ERK1/2 (T202/Y204) detects endogenous levels of p-ERK1/2 protein.. Species:. Human, Mouse, Rat. ...
"Entrez Gene: STK38 serine/threonine kinase 38". Tripodis N, Mason R, Humphray SJ, et al. (1999). "Physical map of human 6p21.2- ... 2004). "Structure of the Ca2+/S100B/NDR kinase peptide complex: insights into S100 target specificity and activation of the ... Serine/threonine-protein kinase 38 is an enzyme that in humans is encoded by the STK38 gene. GRCh38: Ensembl release 89: ... Bichsel SJ, Tamaskovic R, Stegert MR, Hemmings BA (2005). "Mechanism of activation of NDR (nuclear Dbf2-related) protein kinase ...
Mediates also the SAP/JNK signaling pathway and the p38 MAPKs signaling pathway through activation of the MAP3Ks MAP3K10/MLK2 ... Acts as a MAPK kinase kinase kinase (MAP4K) and is an upstream activator of the stress-activated protein kinase/c-Jun N- ... Required for the efficient activation of JNKs by TRAF6-dependent stimuli, including pathogen-associated molecular patterns ( ... terminal kinase (SAP/JNK) signaling pathway and to a lesser extent of the p38 MAPKs signaling pathway. ...
mRNA analyses show that the dual specificity MAP kinase phosphatase MKP-1, a transcriptionally regulated immediate early gene- ... upstream of JNK activation Furthermore, similar to cAMP, TUDC induced a protein kinase A (PKA)-sensitive serine/threonine ... triggers an activation of the Src family kinase Yes and activation of the c-Jun-N-terminal kinase-1/-2 (JNK). The activated Yes ... increased ceramide formation and activation of the protein kinase Cζ (PKCζ) followed by an oxidative stress response via serine ...
... leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Depending on the cellular ... RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 ... cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. ... Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of ...
  • During this period, together with colleagues at the Garvan Institute, he developed novel methodologies for studying in vivo glucose metabolism in small animals leading to a number of important discoveries about the role of tissue specificity of insulin action at the whole body level. (edu.au)
  • Although the molecular mechanisms by which the HIV-1 triggers either T cell activation, anergy, or apoptosis remain poorly understood, it is well established that the interaction of HIV-1 envelope glycoproteins with cell surface CD4 delivers signals to the target cell, resulting in activation of transcription factors such as NF-κB and AP-1. (jimmunol.org)
  • More recently, we and others ( 15 , 16 , 17 , 18 ) demonstrated that the binding of heat-inactivated HIV-1 (iHIV-1) or gp120/anti-gp120 immune complexes to the cell surface CD4 molecule enhances the DNA-binding activity of NF-κB and AP-1 transcription factors in CD4 + T lymphoblastoid cell line and primary T lymphocytes. (jimmunol.org)
  • TANK-binding kinase-1 (TBK1) and the inducible IκB kinase (IKK- i ) have been shown recently to activate interferon (IFN) regulatory factor-3 (IRF3), the primary transcription factor regulating induction of type I IFNs. (rupress.org)
  • Con sistent with these data, B‐RafAA and B‐RafED exhibited diminished and enhanced ability, respectively, to stimulate ERK activation and Elk‐dependent transcription. (embopress.org)
  • Substrates of ERKs include additional protein kinases such as MAPKAP-kinase, signaling molecules such as phos-pholipases, and transcription factors such as Elk-1/ternary complex factor . (guwsmedical.info)
  • Genomic and biochemical insights into the specificity of ETS transcription factors. (nih.gov)
  • This kinase targets specific transcription factors, and thus mediates immediate-early gene expression in response to various cell stimuli. (wikidoc.org)
  • PYST2-S may act as a negative regulator of PYST2-L although it is unclear whether this is by competing for transcription, translation or activation factors. (hmdb.ca)
  • The protein encoded by this gene is a member of the MAP kinase family. (wikipedia.org)
  • Serine/threonine-protein kinase 38 is an enzyme that in humans is encoded by the STK38 gene. (wikipedia.org)
  • Because activation of the EGFR leads to activation of the intracellular effector KRAS, it was hypothesized that mutations in the KRAS coding gene could lead to a constitutively activated KRAS protein that is independent from upstream signals, which subsequently could affect clinical response to EGFR inhibitors. (aacrjournals.org)
  • These different layers of defense include basal defense and resistance (R) 1 -gene-mediated defenses. (mcponline.org)
  • A specific match between an avirulence gene product and the corresponding R-gene product leads to hypersensitive response and activation of defense responses. (mcponline.org)
  • In addition to R-gene-mediated defense plants rely on recognition of general elicitors, also called pathogen-associated molecular patterns, to detect potential pathogens and to activate basal defense ( 1 ). (mcponline.org)
  • This gene and MAPK8 are also known as c-Jun N-terminal kinases. (wikidoc.org)
  • Cdk9 activation is essential in tissue culture for myocyte enlargement and sufficient in transgenic mice for hypertrophy to occur and yet is unrelated to the "fetal" gene program that is typical of pathophysiological heart growth. (ahajournals.org)
  • The boxes indicate coding regions (exon 1-12) of the gene. (atlasgeneticsoncology.org)
  • The most updated data on the National Center for Biotechnology Information (NCBI) and new publications, mapped human GLI3 to chromosome 7p14.1 (Gene ID:2737, (biomedcentral.com)
  • p75NTR mediates signaling of the myelin-associated and growth inhibitory molecules MAG, Nogo-66 and OMgp though association with the Nogo-receptor and the transmembrane protein LINGO-1. (sigmaaldrich.com)
  • These are essentially traditional NSAIDs which can either have nitric oxide- (NO-) donating moieties, hydrogen sulphide- (H 2 S-) donating moieties, or phosphate moieties covalently attached to the -COOH site via aromatic or aliphatic spacer molecules, as shown in Figure 1 . (hindawi.com)
  • Plant genomes encode a large number of surface receptor-like kinases (RLKs) to perceive different signals from both distal cells responding to stresses such as herbivore feeding or to the presence of pathogens through detection of non-self molecules ( Shiu and Bleecker, 2001 ). (frontiersin.org)
  • The present invention specifically provides isolated peptide and nucleic acid molecules, methods of identifying orthologs and paralogs of the kinase peptides, and methods of identifying modulators of the kinase peptides. (patentgenius.com)
  • Such clustering of signaling molecules is now recognized as a common means to achieve specificity and to counter entropic forces that tend to equalize cellular protein distribution. (guwsmedical.info)
  • Public Health 2004, 1 identify a peptide in association with major histocompatibility complex (MHC) class II or class I molecules on target cells. (healthdocbox.com)
  • A ) Assembly of modular signaling molecules on an activated receptor tyrosine kinase. (sciencemag.org)
  • 1 2 The ligation of HGF to its receptor, c-Met, produces activation and recruitment of multiple signaling molecules that are probably involved in diverse responses. (arvojournals.org)