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.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)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.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.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.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).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.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.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.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.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 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).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.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.Systems Biology: Comprehensive, methodical analysis of complex biological systems by monitoring responses to perturbations of biological processes. Large scale, computerized collection and analysis of the data are used to develop and test models of biological systems.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.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.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.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.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 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.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.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.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.MAP Kinase Kinase 6: A mitogen-activated protein kinase kinase with specificity for P38 MITOGEN-ACTIVATED PROTEIN KINASES.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.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.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.Kinetics: The rate dynamics in chemical or physical systems.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes.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.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.Life Support Systems: Systems that provide all or most of the items necessary for maintaining life and health. Provisions are made for the supplying of oxygen, food, water, temperature and pressure control, disposition of carbon dioxide and body waste. The milieu may be a spacecraft, a submarine, or the surface of the moon. In medical care, usually under hospital conditions, LIFE SUPPORT CARE is available. (From Webster's New Collegiate Dictionary)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.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.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.Ecological Systems, Closed: Systems that provide for the maintenance of life in an isolated living chamber through reutilization of the material available, in particular, by means of a cycle wherein exhaled carbon dioxide, urine, and other waste matter are converted chemically or by photosynthesis into oxygen, water, and food. (NASA Thesaurus, 1988)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.Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task.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.Flavonoids: A group of phenyl benzopyrans named for having structures like FLAVONES.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.Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories for solving biological problems including manipulation of models and datasets.Proteins: 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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.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.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.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.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.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.Synthetic Biology: A field of biological research combining engineering in the formulation, design, and building (synthesis) of novel biological structures, functions, and systems.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.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.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.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.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.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).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.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.Pyruvate 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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.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.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.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Software: Sequential operating programs and data which instruct the functioning of a digital computer.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.Thymidine 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.Gene Regulatory Networks: Interacting DNA-encoded regulatory subsystems in the GENOME that coordinate input from activator and repressor TRANSCRIPTION FACTORS during development, cell differentiation, or in response to environmental cues. The networks function to ultimately specify expression of particular sets of GENES for specific conditions, times, or locations.PhosphoproteinsRecombinant 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.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.Phosphotransferases (Alcohol Group Acceptor): A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.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.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.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Cell Line, Tumor: A cell line derived from cultured tumor cells.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.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.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.Butadienes: Four carbon unsaturated hydrocarbons containing two double bonds.Biology: One of the BIOLOGICAL SCIENCE DISCIPLINES concerned with the origin, structure, development, growth, function, genetics, and reproduction of animals, plants, and microorganisms.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.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.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.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.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.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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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.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.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.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.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.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.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.Aurora 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.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.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.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Androstadienes: Derivatives of the steroid androstane having two double bonds at any site in any of the rings.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.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.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)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.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).Stochastic Processes: Processes that incorporate some element of randomness, used particularly to refer to a time series of random variables.Metabolic Networks and Pathways: Complex sets of enzymatic reactions connected to each other via their product and substrate metabolites.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.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.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.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.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.Proteomics: The systematic study of the complete complement of proteins (PROTEOME) of organisms.Biological Phenomena: Biological processes, properties, and characteristics of the whole organism in human, animal, microorganisms, and plants, and of the biosphere.Protein Interaction Mapping: Methods for determining interaction between PROTEINS.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.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.ChromonesRats, 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.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.Focal Adhesion Protein-Tyrosine Kinases: A family of non-receptor, PROLINE-rich protein-tyrosine kinases.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.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.Nitriles: Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.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.Mass Spectrometry: An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.Models, Genetic: Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Models, Theoretical: Theoretical representations that simulate the behavior or activity of systems, processes, or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.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.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.Proteome: The protein complement of an organism coded for by its genome.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.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.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)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.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.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.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.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.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.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.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.MorpholinesCell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Oligonucleotide Array Sequence Analysis: Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.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.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.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 enzymesFibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.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.Models, Chemical: Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.Protein 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.Maps as Topic: Representations, normally to scale and on a flat medium, of a selection of material or abstract features on the surface of the earth, the heavens, or celestial bodies.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.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.Protein Phosphatase 1: A eukayrotic protein serine-threonine phosphatase subtype that dephosphorylates a wide variety of cellular proteins. The enzyme is comprised of a catalytic subunit and regulatory subunit. Several isoforms of the protein phosphatase catalytic subunit exist due to the presence of multiple genes and the alternative splicing of their mRNAs. A large number of proteins have been shown to act as regulatory subunits for this enzyme. Many of the regulatory subunits have additional cellular functions.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.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.Biological Processes: Biological activities and function of the whole organism in human, animal, microorgansims, and plants, and of the biosphere.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.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.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.Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome.Mitogen-Activated Protein Kinase Phosphatases: A subcategory of phosphohydrolases that are specific for MITOGEN-ACTIVATED PROTEIN KINASES. They play a role in the inactivation of the MAP KINASE SIGNALING SYSTEM.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.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.MAP Kinase Kinase 5: A mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 7.Cell Physiological Phenomena: Cellular processes, properties, and characteristics.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.Cyclic GMP-Dependent Protein Kinases: A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.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.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.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.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.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.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).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.Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.Biological Products: Complex pharmaceutical substances, preparations, or matter derived from organisms usually obtained by biological methods or assay.Models, Statistical: Statistical formulations or analyses which, when applied to data and found to fit the data, are then used to verify the assumptions and parameters used in the analysis. Examples of statistical models are the linear model, binomial model, polynomial model, two-parameter model, etc.Cells: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.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.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.Receptor, Epidermal Growth Factor: A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.

*Gaseous signaling molecules

Nitrous oxide in biological systems can be formed by an enzymatic or non-enzymatic reduction of nitric oxide. In vitro studies ... inhibits vascular smooth muscle cell proliferation via suppressing the Erk/MAP kinase pathway mediated by cAMP/PKA signaling". ... Wang XB, Jin HF, Tang CS, Du JB (16 Nov 2011). "The biological effect of endogenous sulfur dioxide in the cardiovascular system ... The biological roles of each of the gaseous signaling molecules are in short outlined below. Gasotransmitters is a subfamily of ...

*Ultrasensitivity

"Using Engineered Scaffold Interactions to Reshape MAP Kinase Pathway Signaling Dynamics". Science. 319 (5869): 1539-43. Bibcode ... and implicated the importance of this in many biological systems. Many biological processes are binary (ON-OFF), such as cell ... This is especially relevant for large cascades, such as the flagellar regulatory system in which the master regulator signal is ... In mitogen-activated protein kinase (MAPK) signaling (see example below), the ultrasensitivity of the signaling is supported by ...

*MAPK14

MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular ... p38α MAPK is mainly activated through MAPK kinase kinase cascades and exerts its biological function via downstream substrate ... p38γ MAPK mostly in skeletal muscle and nerve system, and p38δ MAPK in uterus and pancreas. Like all MAP kinases, p38α MAPK has ... p38α MAPK mediated kinase activity has been implicated in many tissues beyond immune systems. ...

*Chemical biology

... are potent inhibitors useful in the dissection of MAP kinase signaling pathways. These pyridinylimidazole compounds function by ... When the probe is added to a biological system, it will selectively conjugate with the target molecule. The most common method ... Some forms of chemical biology attempt to answer biological questions by directly probing living systems at the chemical level ... Pargellis C, Ton L, Churchill L, CIrillo PF, Gilmore T, Graham AG, Grob PM, Hickey ER, Moss N (2002). "p38 MAP kinase". Nature ...

*Scutellaria

"Anti-inflammatory effects of Scutellaria baicalensis extract via suppression of immune modulators and MAP kinase signaling ... Huang, Yu; Tsang, Suk-Ying; Yao, Xiaoqiang; Chen, Zhen-Yu (2005). "Biological Properties of Baicalein in Cardiovascular System ... Skullcaps are common herbal remedies in systems of traditional medicine. In traditional Chinese medicine they are utilized to " ... Awad R, Arnason JT, Trudeau V, Bergeron C, Budzinski JW, Foster BC, Merali Z (2003). "Phytochemical and biological analysis of ...

*Integrin-linked kinase

"Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3: 89. doi:10.1038/ ... Integrin-linked kinase is an enzyme that in humans is encoded by the ILK gene involved with integrin-mediated signal ... critical roles for kinase activity and amino acids arginine 211 and serine 343". The Journal of Biological Chemistry. 276 (29 ... ILK1 has been found in the root system of most plants where they are co-localized on the plasma membrane and endoplasmic ...

*HER2/neu

Huang YZ, Zang M, Xiong WC, Luo Z, Mei L (January 2003). "Erbin suppresses the MAP kinase pathway". The Journal of Biological ... mitogen-activated protein kinase (MAPK) phosphoinositide 3-kinase (PI3K/Akt) phospholipase C γ protein kinase C (PKC) Signal ... Schulze WX, Deng L, Mann M (2005). "Phosphotyrosine interactome of the ErbB-receptor kinase family". Molecular Systems Biology ... subunit of the phosphatidylinositol 3-kinase complex and a related p85 beta protein by using the baculovirus expression system ...

*List of MeSH codes (G06)

... map kinase signaling system MeSH G06.184.850.580 --- mechanotransduction, cellular MeSH G06.184.850.700 --- phototransduction ... MeSH G06.184.850.800 --- second messenger systems MeSH G06.184.850.800.100 --- calcium signaling MeSH G06.184.850.850 --- ... biological transport, active MeSH G06.535.166.310.100 --- active transport, cell nucleus MeSH G06.535.166.310.657 --- membrane ... protein sorting signals MeSH G06.184.603.060.670.600 --- nuclear export signals MeSH G06.184.603.060.670.610 --- nuclear ...

*Phosphorylation

... as part of the insulin signaling pathway. Phosphorylation of src tyrosine kinase (pronounced "sarc") by C-terminal Src kinase ( ... "Histidine phosphorylation in biological systems". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1784 (1): 100- ... Schoeberl, B; Eichler-Jonsson, C; Gilles, ED; Müller, G (Apr 2002). "Computational modeling of the dynamics of the MAP kinase ... Chang C, Stewart RC (July 1998). "The Two-Component System. Regulation of Diverse Signaling Pathways in Prokaryotes and ...

*Xenopus

... embryos and eggs are a popular model system for a wide variety of biological studies. This animal is used because of ... such as the MAP kinase pathway and the Wnt pathway. Moreover, new methods using egg extracts revealed novel, important targets ... Signal transduction: Xenopus embryos and cell-free extracts are widely used for basic research in signal transduction. In just ... "Interferon activity produced by translation of human interferon messenger RNA in cell-free ribosomal systems and in Xenopus ...

*ACOT2

A number of other cellular events are also mediated via acyl-CoAs, for example signal transduction through protein kinase C, ... "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi: ... A new role for long chain fatty acid acylation of proteins". The Journal of Biological Chemistry. 269 (9): 6498-505. PMID ... inhibition of retinoic acid-induced apoptosis, and involvement in budding and fusion of the endomembrane system. Acyl-CoAs also ...

*Arsenic poisoning

MAP] kinases, extracellular regulated kinase [ERK], c-jun terminal kinases [JNK] and p38. Via JNK and p38 it activates c-fos, c ... January 1998). "The stress inducer arsenite activates mitogen-activated protein kinases extracellular signal-regulated kinases ... The current biological exposure index for U.S. workers of 35 µg/L total urinary arsenic may easily be exceeded by a healthy ... Chronic arsenic exposure can remain in the body systems for a longer period of time than a shorter term or more isolated ...

*Metastatic breast cancer

MAP) kinases. Heparanase cleaves heparin sulfate chains of HSPGs, which have an extensive network with several proteins on the ... and causes activation of the signaling tyrosine kinase receptors even under low circulating concentrations of growth factors. ... There is increased expression of protease systems in cancer cells, to equip them with the tools necessary to degrade the ... biological, and hormonal therapy. Typical environmental barriers in a metastatic event include physical (a basement membrane), ...

*T helper cell

Cellular auto-immune disease occurs because the host antigen recognition systems fail, and the immune system believes, by ... "Interleukin-10 production by Th1 cells requires interleukin-12-induced STAT4 transcription factor and ERK MAP kinase activation ... Verification (signal 2)[edit]. Having received the first TCR/CD3 signal, the naïve T cell must activate a second independent ... "Molecular and biological characterization of a murine ligand for CD40". Nature. 357 (6373): 80-2. doi:10.1038/357080a0. PMID ...

*Kisspeptin

... extracellular signal-regulated protein kinase 1 (ERK1), ERK2, and p38 MAP kinase phosphorylation.[8] Although GnRH is located ... Several studies have confirmed that addition of kisspeptin to biological systems including rat, mouse, and sheep are able to ... In a study where malignant tumor cells were injected into a model system, the system was then tested for genes involved in the ... Biological process. • negative regulation of cell proliferation. • positive regulation of synaptic transmission. • positive ...

*Caenorhabditis elegans

... this system comprises 302 neurons[54] the pattern of which has been comprehensively mapped, in what is known as a connectome, ... elegans life-span by insulinlike signaling in the nervous system". Science. 290 (5489): 147-50. Bibcode:2000Sci...290..147W. ... "The Journal of Biological Chemistry. 283 (1): 350-7. doi:10.1074/jbc.M705028200. PMC 2739662. PMID 17959600.. ... C. elegans is an unsegmented pseudocoelomate and lacks respiratory or circulatory systems.[11] Most of these nematodes are ...

*Arabidopsis thaliana

... the most notable one being the mitogen-activated protein kinase (MAP kinase) cascade. Downstream responses of PTI include ... Many model systems have been developed to better understand interactions between plants and bacterial, fungal, oomycete, viral ... Both FLS2 and EFR use similar signal transduction pathways to initiate PTI. A. thaliana has been instrumental in dissecting ... Mitchell-Olds T (December 2001). "Arabidopsis thaliana and its wild relatives: a model system for ecology and evolution". ...

*Spatial memory

Thus, we have to make certain assumptions about the interaction between these two systems. For example, cognitive maps are not ... Hebert, A. E.; Dash, P. K. (2002). "Extracellular signal-regulated kinase activity in the entorhinal cortex is necessary for ... One can recall from only one at region at a time (a bottleneck). A bottleneck in a person's cognitive navigational system could ... Progress in Neuro-Psychopharmacology and Biological Psychiatry. 30 (2): 223-229. doi:10.1016/j.pnpbp.2005.10.018. PMID 16356617 ...

*Gephyrin

Thiriet, Marc (2013). Intracellular Signaling Mediators in the Circulatory and Ventilatory Systems. New York, NY: Springer New ... Biological process. • gamma-aminobutyric acid receptor clustering. • glycine receptor clustering. • Mo-molybdopterin cofactor ... Lorenzo LE, Barbe A, Bras H (March 2004). "Mapping and quantitative analysis of gephyrin cytoplasmic trafficking pathways in ... a possible link to the microfilament system". J. Neurosci. 23 (23): 8330-9. doi:10.1523/JNEUROSCI.23-23-08330.2003. PMC 6740687 ...

*Superantigen

This alternative signaling pathway impairs the calcium/calcineurin and Ras/MAPkinase pathways slightly,[14] but allows for a ... Both the protein kinase C pathway and the protein tyrosine kinase pathways are activated, resulting in upregulating production ... The biological strength of the SAg (its ability to stimulate) is determined by its affinity for the TCR. SAgs with the highest ... SAgs are produced by some pathogenic viruses and bacteria most likely as a defense mechanism against the immune system.[1] ...

*PRNP

The PrP-activated signal transduction pathway is associated with axon and dendritic outgrowth with a series of kinases.[25][46] ... Immune systemEdit. Though most attention is focused on PrP's presence in the nervous system, it is also abundant in immune ... Biological process. • negative regulation of protein phosphorylation. • negative regulation of interferon-gamma production. • ... Liao YC, Lebo RV, Clawson GA, Smuckler EA (July 1986). "Human prion protein cDNA: molecular cloning, chromosomal mapping, and ...

*CDC42

"The MAP kinase kinase kinase MLK2 co-localizes with activated JNK along microtubules and associates with kinesin superfamily ... Biological process. • cardiac conduction system development. • positive regulation of protein phosphorylation. • negative ... a Rho family GTPase-activating protein that interacts with signaling adapters Gab1 and Gab2". The Journal of Biological ... "Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948 . PMID 17353931.. ...

*Somatic evolution in cancer

Evolution in complex biological systems[edit]. Modern descriptions of biological evolution will typically elaborate on major ... another receptor tyrosine kinase, which can bypass EGFR to activate downstream signaling in the cell. In an initial study, 22% ... Mapping between common terms from cancer biology and evolutionary biology *Driver mutation = a mutation that gives a selective ... System instability is a major contributing factor for genetic heterogeneity.[42] For the majority of cancers, genome ...

*Proteasome

Karin M, Delhase M (February 2000). "The I kappa B kinase (IKK) and NF-kappa B: key elements of proinflammatory signalling". ... The overall system of ubiquitination and proteasomal degradation is known as the ubiquitin-proteasome system.[3] ... "The Journal of Biological Chemistry. 262 (17): 8303-13. PMID 3298229.. *^ Hershko A (September 2005). "Early work on the ... whereas some protists possess both the 20S and the hslV systems.[75] Many bacteria also possess other homologs of the ...

*Tumor necrosis factor alpha

"TNF-stimulated MAP kinase activation mediated by a Rho family GTPase signaling pathway". Genes Dev. 25 (19): 2069-78. doi: ... The theory of an anti-tumoral response of the immune system in vivo was recognized by the physician William B. Coley. In 1968, ... Biological process. • regulation of protein phosphorylation. • positive regulation of protein phosphorylation. • positive ... It has a number of actions on various organ systems, generally together with IL-1 and Interleukin-6 (IL-6): ...
Recombinant Calcium/calmodulin-Dependent Protein Kinase IV (CAMK4) Protein (His tag). Spezies: Human. Quelle: Escherichia coli (E. coli). Jetzt Produkt ABIN668012 bestellen.
TY - JOUR. T1 - Mutational analysis of Ca2+-independent autophosphorylation of calcium/calmodulin-dependent protein kinase II. AU - Mukherji, Sucheta. AU - Soderling, Thomas. PY - 1995/6/9. Y1 - 1995/6/9. N2 - Previous studies with synthetic peptides indicate that residues 290-309, corresponding to the calmodulin (CaM)-binding domain of Ca2+/CaM-dependent protein kinase II interact with the catalytic core of the enzyme as a pseudosubstrate (Colbran, R. J., Smith, M. K., Schworer, C. M., Fong, Y. L., and Soderling, T. R. (1989) J. Biol. Chem. 264, 4800-4804). In the present study, we attempted to locate the pseudosubstrate motif by generation or removal of potential substrate recognition sequences (RXXS/T) at selected positions using site-directed mutagenesis. Based on previous results, Arg297, Thr305/306, and Ser314 were selected as key residues. Single mutations such as N294S, K300S, A302R, A309R, and R311A were expressed, purified, and characterized. Several of the mutants ...
The p38 mitogen-activated protein (MAP) kinase signal transduction pathway is activated by proinflammatory cytokines and environmental stress. The detection of p38 MAP kinase in the nucleus of activated cells suggests that p38 MAP kinase can mediate signaling to the nucleus. To test this hypothesis, we constructed expression vectors for activated MKK3 and MKK6, two MAP kinase kinases that phosphorylate and activate p38 MAP kinase. Expression of activated MKK3 and MKK6 in cultured cells caused a selective increase in p38 MAP kinase activity. Cotransfection experiments demonstrated that p38 MAP kinase activation causes increased reporter gene expression mediated by the transcription factors ATF2 and Elk-1. These data demonstrate that the ...
Raingeaud J., Whitmarsh A.J., Barrett T., Derijard B., Davis R.J.. The p38 mitogen-activated protein (MAP) kinase signal transduction pathway is activated by proinflammatory cytokines and environmental stress. The detection of p38 MAP kinase in the nucleus of activated cells suggests that p38 MAP kinase can mediate signaling to the nucleus. To test this hypothesis, we constructed expression vectors for activated MKK3 and MKK6, two MAP kinase kinases that phosphorylate and activate p38 MAP kinase. Expression of activated MKK3 and MKK6 in cultured cells caused a selective increase in p38 MAP kinase activity. Cotransfection experiments demonstrated that p38 MAP kinase activation causes increased reporter gene expression mediated by the ...
Results We show that culture of MRL/lpr Foxp3-GFP T cells in the presence of KN-93 promotes Treg differentiation in a dose dependent manner (Fig. F). Treatment of MRL/lpr Foxp3-GFP mice with KN-93 results in significant induction of Treg cells in the spleen, peripheral lymph nodes (Fig. B-E) and peripheral blood (Fig. A and B) and this is accompanied by decreased skin and kidney damage. Notably, KN-93 clearly diminishes the accumulation of inflammatory cells along with reciprocally increased Treg cells in target organ.. ...
TY - JOUR. T1 - Amphetamine activate protein kinase C and calcium/calmodulin-dependent protein kinase via NMDA receptor in primary cultures of rat cortical neurons. AU - Wu, Hsueh-Hsia. AU - Lee, Horng-Mo. PY - 1999. Y1 - 1999. M3 - Article. VL - 1. SP - 12. EP - 19. JO - New Taipei Journal of Medicine. JF - New Taipei Journal of Medicine. SN - 1562-4242. ER - ...
TABLE-US-00001 TABLE 1 Oligo Accession Gene ID Number Number number Gene Name Symbol APOB-10167- 12138 NM_000384 Apolipoprotein B (including Ag(x) antigen) APOB 20-12138 APOB-10167- 12139 NM_000384 Apolipoprotein B (including Ag(x) antigen) APOB 20-12139 MAP4K4-2931- 12266 NM_004834 Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 MAP4K4 13-12266 (MAP4K4), transcript variant 1 MAP4K4-2931- 12293 NM_004834 Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 MAP4K4 16-12293 (MAP4K4), transcript variant 1 MAP4K4-2931- 12383 NM_004834 Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 MAP4K4 16-12383 (MAP4K4), transcript variant 1 ...
Although classic genetic analyses, such as those described above, have revealed much about the molecular pathways involved in artery-vein specification, such approaches have limitations when it comes to examining signaling pathways that function at multiple stages in development. With a typical nonconditional mutation, the primary role for a gene at later stages of development is often difficult to distinguish from indirect consequences of disrupting the gene at an earlier stage. The Hedgehog pathway, for example, plays a critical role in vasculogenesis, but is also involved in development of numerous other structures at various developmental time points.34 Moreover, classic genetic approaches can be hampered by genetic redundancy.35 A powerful alternative approach, chemical genetic analysis, can overcome the challenges posed by repeated utilization of a signaling pathway during development and by genetic redundancy. Recently, Hedgehog signaling inhibitor ...
Authors Affiliations: 1Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Istituto di Endocrinologia e Oncologia Sperimentale del CNR Naples; 2Department of Neuroscience, Reproductive and Odontostomatological Sciences, University of Naples "Federico II", Naples; 3Department of Medicine-DIMED, Unit of Endocrinology, University of Padua, Padova; and 4Department of Medicine and Surgery, University of Salerno, Salerno, ...
PGC-1α-dependent irisin, a novel myokine, is derived from cleaving Fndc5 protein. Irisin promotes brown fat-like development and thermogenesis in WAT both in vitro and in vivo. The discovery of irisin has created an opportunity to further understand the role of adipocytes in obesity, diabetes, and other associated metabolic disorders (12,13,26,27). However, the molecular mechanisms and cellular signaling pathways responsible for the browning effect of irisin have not been elucidated.. In this study, we successfully constructed the yeast expression plasmid containing a synthesized optimal codon usage, human irisin-coding sequence and generated pure human recombinant irisin protein in P. pastoris with high yield that is fully biologically functional. The P. pastoris system is widely used for heterogenic protein expression, with the capacity to generate posttranslational modified proteins (28). The human recombinant irisin protein expressed in yeast showed a ...
Defective heme synthesis in mammals has been suspected of causing neuropathy associated with porphyrias and lead poisoning. To determine the molecular action of heme in neuronal cells, we examined the effect of the inhibition of heme synthesis on nerve growth factor (NGF) signaling in PC12 cells. We found that the inhibition of heme synthesis by succinyl acetone interferes with NGF-induced neurite outgrowth in PC12 cells. Furthermore, we show that heme deficiency obliterates the activation of the signaling intermediates of the Ras-mitogen-activated protein kinase signaling pathway and its downstream target, the transcription activator cyclic AMP response element-binding protein. Strikingly, microarray expression analysis shows that the inhibition of heme synthesis selectively diminishes the induction of expression of a subset of neuron-specific genes by NGF, such as Ras and neurofilament proteins, whereas NGF induces the expression of ...
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We have previously reported the in vitro pharmacological properties of E6201, including the following: 1) E6201 suppressed the activation of AP-1 via inhibitory effects on mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-1 and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase-; 2) E6201 decreased activation of NF-κB; 3) E6201 suppressed the production of various proinflammatory cytokines in human monocytes and leukocytes; and 4) E6201 attenuated hyperproliferation and IL-8 production in human keratinocytes in vitro (Goto et al., 2009). These pharmacological properties of E6201 indicate that this compound represents a promising strategy for the treatment of psoriasis, because psoriasis is a chronic inflammatory skin disease characterized by severe hyperplasia in the epidermis and marked infiltration of leukocytes into dermis and ...
TY - JOUR. T1 - Sphingosine 1-phosphate stimulation of the p42/p44 mitogen-activated protein kinase pathway in airway smooth muscle. Role of endothelial differentiation gene 1, c-Src tyrosine kinase and phosphoinositide 3-kinase. AU - Rakhit, S. AU - Conway, A M. AU - Tate, R. AU - Bower, T. AU - Pyne, N J. AU - Pyne, S. PY - 1999/3/15. Y1 - 1999/3/15. N2 - We report here that cultured airway smooth muscle cells contain transcripts of endothelial differentiation gene 1 (EDG-1), a prototypical orphan Gi-coupled receptor whose natural ligand is sphingosine 1-phosphate (S1P). This is consistent with data that showed that S1P activated both c-Src and p42/p44 mitogen-activated protein kinase (p42/p44 MAPK) in a pertussis toxin (PTX)-sensitive manner in these cells. An essential role for c-Src was confirmed by using the c-Src inhibitor, PP1, which markedly decreased p42/p44 MAPK activation. We have also shown that ...
MAP kinases are key mediators of cellular differentiation and proliferation in all animals, and they function in receptor tyrosine kinase/Ras signaling pathways (reviewed in Marshall 1994). MAP kinase plays an important role in the Ras signaling pathway because it can activate downstream substrates that directly mediate the cellular response to growth factors, suggesting that MAP kinase acts near or at the end of this signaling pathway (reviewed in Treisman 1996).. MAP kinases are activated when they become phosphorylated by the protein kinase MEK (MAP or ERK kinase; Adams and Parker 1992; Crewset al. 1992b). The major known substrate for MEK is currently MAP kinase, suggesting that the predominant function of MEK may be to ...
Complete information for CAMK4 gene (Protein Coding), Calcium/Calmodulin Dependent Protein Kinase IV, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Fertilization of metaphase II-arrested mouse eggs results in resumption of meiosis and a decrease in both cdc2/cyclin B kinase and MAP kinase activities; the decrease in cdc2/cyclin B kinase activity precedes the decrease in MAP kinase activity. Cycloheximide treatment of metaphase II-arrested mouse eggs also results in resumption of meiosis but bypasses the fertilization-induced Ca2+ transient. However, it is not known if cycloheximide treatment results in the same temporal changes in cdc2/cyclin B kinase and MAP kinase activities that are intimately associated with resumption of meiosis. We report that cycloheximide-treated mouse eggs manifest similar temporal changes in the decrease in both cdc2/cyclin B kinase and MAP kinase activities that occur following fertilization, although cortical granule ...
The concept of subcellular targeting by anchoring proteins is of major importance for understanding the specificity of signal transduction. The work presented here constitutes the first description of an anchoring protein for multifunctional CaM kinase II. αKAP exhibits three properties expected of anchoring proteins. (i) It is restricted to a specific cellular compartment, it is membrane bound and probably directly inserted into SR membranes by its N‐terminal hydrophobic domain (Figures 3 and 4). (ii) It binds CaM kinase II. This binding occurs within intact cells and not during extraction of transfected cells, since significant interaction was only detected after coexpression of αKAP and CaM kinase II, but not when individually expressed proteins were mixed (Figure 6). (iii) It is responsible for the targeting of the novel βM‐CaM kinase II to the SR, since it co‐immunoprecipitates with kinase extracted from SR membranes ...
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
Peptides , Myelin Oligodendrocyte Glycoprotein (MOG),Myelin Basic Proteins (MBP) , MBP, MAPK Substrate, Biotinylated, Phosphorylated; This is an N-terminally biotinylated peptide, with a phosphorylated Thr97. The sequence APRTPGGRR contains a native sequence derived from bovine myelin basic protein amino acids 95-98 (PRTP). The rest of the sequence is not derived from a native sequence, but is a synthetic construct. APRTPGGRR is specific for MAP kinases: p44MAPK [extracellular signal-regulated kinase 1 (ERK1)] and p42MAPK (ERK2). It contains the consensus sequence Pro-X-(Ser/Thr)-Pro that is recognized by MAP kinase. APRTPGGRR is the most efficient substrate for phosphorylation reaction by ERK and is phosphorylated by kinases on threonine 97 and can also be phosphorylated by MAPK p38.; Biotin-APR-pT-PGGRR; ...
In the present study, we established a novel function for LX acting on a previously unappreciated cell target, namely, human T cells. Both 15-epi-LXA4 and LXB4 inhibited TNF-α secretion from PBMC stimulated by anti-CD3 Abs. We also found that stable analogs of 15-epi-LXA4 and LXB4, namely, ATLa1, ATLa2, and 5-(R/S)-methyl-LXB4, each share this activity and inhibit TNF-α secretion to a similar extent as their corresponding origins, implying that these analogs could be used for improved in vivo treatment of T cell-mediated inflammation. Most results obtained to date indicate that TNF-α, which is produced by T cells upon stimulation by Ags, is also critical for the establishment of chronic inflammatory disorders such as arthritis, inflammatory bowel disease, and others (20, 37), and therefore serves as a primary target for therapeutic intervention (21, 38). Of interest, TNF-α also plays a role in the resolution phase of inflammation (18, 39), rendering the regulation of its bioavailability an ...
TY - JOUR. T1 - Neutrophil elastase induces IL-8 synthesis by lung epithelial cells via the mitogen-activated protein kinase pathway. AU - Chen, Hao Cheng. AU - Lin, Horng Chyuan. AU - Liu, Chien Ying. AU - Wang, Chun Hua. AU - Hwang, Tritium. AU - Huang, Tzu Ting. AU - Lin, Chien-Huang. AU - Kuo, Han Pin. PY - 2004. Y1 - 2004. N2 - The sequestration of neutrophils in the lung and the release of proinflammatory mediators, including neutrophil elastase, are responsible for sepsis-induced microvascular permeability and alveolar epithelial cell damage. To assess the underlying mechanism, human neutrophil elastase (0.01-0.5 μg/ml) was added to cultured A549 epithelial cells in the presence or absence of inhibitors. IL-8 was analyzed by ELISA or by RT-PCR to measure the IL-8 synthesis capacity. Mitogen-activated protein kinase (MAPK) activity was detected by Western blot analysis. Neutrophil elastase dose-dependently increased IL-8 release from cultured A549 ...
TY - JOUR. T1 - Signal transduction pathways regulated by mitogen-activated/extracellular response kinase kinase kinase induce cell death. AU - Johnson, Nancy Lassignal. AU - Gardner, Anne M.. AU - Diener, Katrina M.. AU - Lange-Carter, Carol A.. AU - Gleavy, Janice. AU - Jarpe, Matthew B.. AU - Minden, Audrey. AU - Karin, Michael. AU - Zon, Leonard I.. AU - Johnson, Gary L.. PY - 1996/2/9. Y1 - 1996/2/9. N2 - Mitogen-activated/extracellular response kinase kinase (MEK) kinase (MEKK) is a serine-threonine kinase that regulates sequential protein phosphorylation pathways, leading to the activation of mitogen-activated protein kinases (MAPK), including members of the Jun kinase (JNK)/stress- activated protein kinase (SAPK) family. In Swiss 3T3 and REF52 fibroblasts, activated MEKK induces cell death involving cytoplasmic ...
Tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK), a member of the TNF family, is a multifunctional cytokine that regulates cell growth, migration, and survival principally through a TWEAK receptor, fibroblast growth factor-inducible 14 (Fn14). However, its physiological roles in bone are largely unknown. We herein report various effects of TWEAK on mouse osteoblastic MC3T3-E1 cells. MC3T3-E1 cells expressed Fn14 and produced RANTES (regulated upon activation, healthy T cell expressed and secreted) upon TWEAK stimulation through PI3K-Akt, but not nuclear factor-κB (NF-κB), pathway. In addition, TWEAK inhibited bone morphogenetic protein (BMP)-2-induced expression of osteoblast differentiation markers such as alkaline phosphatase through mitogen-activated protein kinase (MAPK) Erk pathway. Furthermore, TWEAK upregulated RANKL (receptor activation of NF-κB ligand) expression through MAPK Erk pathway in MC3T3-E1 cells. All these effects of ...
Kaur R., Liu X., Gjoerup O., Zhang A., Yuan X., Balk S.P., Schneider M.C., Lu M.L.. The p21-activated kinases (PAKs) contain an N-terminal Cdc42/Rac interactive binding domain, which in the group 1 PAKs (PAK1, 2, and 3) regulates the activity of an adjacent conserved autoinhibitory domain. In contrast, the group 2 PAKs (PAK4, 5, and 6) lack this autoinhibitory domain and are not activated by Cdc42/Rac binding, and the mechanisms that regulate their kinase activity have been unclear. This study found that basal PAK6 kinase activity was repressed by a p38 mitogen-activated protein (MAP) kinase antagonist and could be strongly stimulated by constitutively active MAP kinase kinase 6 (MKK6), an upstream activator of p38 MAP kinases. Mutation of a consensus p38 MAP kinase target site at serine 165 decreased PAK6 ...
Compounds. Compound I [IUPAC name: N-(3-fluoro-4-((7-methoxy-4-quinolinyl)oxy)phenyl)-1-(2-hydroxy-2-methylpropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide] was synthesized at Amgen, Inc. The MAPK/extracellular signal-regulated kinase (ERK) kinase 1/2 (MEK1/2) inhibitor U0126 was obtained from Calbiochem.. Cells. KATOIII (gastric), PC3 (prostate), HT-29 (colorectal), Colo205 (colorectal), BxPC3 (pancreatic), and U-87 MG (glioblastoma) cancer cell lines were obtained from the American Type Culture Collection. NIH3T3 TPR-Met or NIH3T3 RON cells were generated by stable transfection of TPR-Met, a constitutively active, ligand-independent form of c-Met ( 31) or wild-type RON in NIH3T3 cells. Cells were grown as monolayers using standard cell culture conditions.. Antibodies and reagents. Antibodies against c-Met (C-12), RON (C-20), and actin (1615-R) were acquired from Santa Cruz Biotechnology. Antibodies against phospho-c-Met (Y1234/1235), ...
The mitogen-activated protein kinase kinase (MEK) kinase 1 (MEKK1) mediates activin B signals required for eyelid epithelium morphogenesis during mouse fetal development. The present study investigates the role of MEKK1 in epithelial wound healing, another activin-regulated biological process. In a skin wound model, injury markedly stimulates MEKK1 expression and activity, which are in turn required for the expression of genes involved in extracellular matrix (ECM) homeostasis. MEKK1 ablation or down-regulation by interfering RNA significantly delays skin wound closure and impairs activation of Jun NH2-terminal kinases, induction of plasminogen activator inhibitor (PAI)-1, and restoration of cell-cell junctions of the wounded epidermis. Conversely, expression of wild-type MEKK1 accelerates reepithelialization of full-thickness skin and corneal debridement wounds by mechanisms involving epithelial cell migration, a cell ...
P164 Angiotensin II (Ang II) promotes arachidonic acid (AA) release via activation of cytosolic phospholipase A2 (cPLA2) and D (PLD) in rabbit vascular smooth muscle cells (VSMC). Ang II also stimulates the Ras/MAP kinase pathway, and MAP kinase activates cPLA2 and PLD in VSMC. The increase in Ras/MAP kinase activity elicited by Ang II in VSMC is mediated by 20-hydroxyeicosatetraenoic acid (HETE) and to a lesser extent by 12(S)-HETE, metabolites of AA generated by cytochrome P450 (CYP) and lipoxygenase (LO), respectively, upon activation of cPLA2 by calcium calmodulin-dependent kinase II. The purpose of this study was to determine if Ang II-induced PLD activation stimulation in VSMC from rabbit aorta is mediated by the Ras/MAP kinase pathway via AA metabolites generated by cPLA2. Ang II (100 nM) increased PLD activity measured as the production of ...
Nerve growth factor (NGF) increases expression of nitric oxide synthase (NOS) isozymes leading to enhanced production of nitric oxide (NO). NOS inhibitors attenuate NGF-mediated increases in cholinergic gene expression and neurite outgrowth. Mechanisms underlying this are unknown, but the mitogen-activated protein (MAP) kinase pathway plays an important role in NGF signaling. Like NGF, NO donors activate Ras leading to phosphorylation of MAP kinase. The present study investigated the role of NO in NGF-mediated activation of MAP kinase in PC12 cells. Cells were treated with 50 ng/mL NGF to establish the temporal pattern for rapid and sustained activation phases of MAP kinase kinase (MEK)-1/2 and p42/p44-MAP kinase. Subsequently, cells were pretreated with NOS inhibitors Nomega-nitro-L-arginine methylester and ...
TY - JOUR. T1 - Lithium protection of phencyclidine-induced neurotoxicity in developing brain. T2 - The role of phosphatidylinositol-3 kinase/Akt and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling pathways. AU - Xia, Yan. AU - Wang, Cheng Z.. AU - Liu, Jie. AU - Anastasio, Noelle. AU - Johnson, Kenneth M.. PY - 2008/9. Y1 - 2008/9. N2 - Phencyclidine (PCP) and other N-methyl-D-aspartate (NMDA) receptor antagonists have been shown to be neurotoxic to developing brains and to result in schizophrenia-like behaviors later in development. Prevention of both effects by antischizophrenic drugs suggests the validity of PCP neurodevelopmental toxicity as a heuristic model of schizophrenia. Lithium is used for the treatment of bipolar and schizoaffective disorders and has recently been shown to have neuroprotective properties. The present study used organotypic corticostriatal slices taken from ...
Three-tiered kinase modules, such as the Raf-MEK (mitogen-activated or extracellular signal-regulated protein kinase kinase)-ERK (extracellular signal-regulated kinase) mitogen-activated protein kinase pathway, are widespread in biology, suggesting that this structure conveys evolutionarily advantageous properties. We show that the three-tiered kinase amplifier module combined with negative feedback recapitulates the design principles of a negative feedback amplifier (NFA), which is used in electronic circuits to confer robustness, output stabilization, and linearization of nonlinear signal amplification. We used mathematical modeling and experimental validation to demonstrate that the ERK pathway has properties of an NFA that (i) converts intrinsic switch-like activation kinetics into graded linear responses, (ii) conveys robustness to changes in rates of reactions within the NFA module, and (iii) ...
p42 MAP Kinase (Mitogen-Activated Protein Kinase, MAPK), also known as Erk2 (Extracellular signal-regulated kinase 2) is one of two isoforms of MAP kinase family. It is a serine/threonine protein kinase
This gene product is a 626-amino acid polypeptide that is 96.5% identical to mouse Mekk3. Its catalytic domain is closely related to those of several other kinases, including mouse Mekk2, tobacco NPK, and yeast Ste11. Northern blot analysis revealed a 4.6-kb transcript that appears to be ubiquitously expressed. This protein directly regulates the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by activating SEK and MEK1/2 respectively; it does not regulate the p38 pathway. In cotransfection assays, it enhanced transcription from a nuclear factor kappa-B (NFKB)-dependent reporter gene, consistent with a role in the SAPK pathway. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008 ...
Growth factors and various cellular stresses are known to activate mitogen-activated protein (MAP) kinase, which plays a role in conveying signals from the cytosol to the nucleus. The phosphorylation of MAP kinase is thought to be a prerequisite for translocation. Here, we investigate the translocation and activation of MAP kinase during ischaemia and reperfusion in perfused rat heart. Ischaemia (0-40 min) induces the translocation of MAP kinase from the cytosol fraction to the nuclear fraction. Immunohistochemical observation shows that MAP kinase staining in the nucleus is enhanced after ischaemia for 40 min. Unexpectedly, tyrosine phosphorylation of MAP kinase is unchanged in the nuclear fraction during ischaemia, indicating that unphosphorylated MAP kinase translocates ...
Phosphorylation of the C terminus of c-Fos has been implicated in serum response element-mediated repression of c-fos transcription after its induction by serum growth factors. The growth-regulated enzymes responsible for this phosphorylation in early G1 phase of the cell cycle and the sites of phosphorylation have not been identified. We now provide evidence that two growth-regulated, nucleus- and cytoplasm-localized protein kinases, 90-kDa ribosomal S6 kinase (RSK) and mitogen-activated protein kinase (MAP kinase), contribute to the serum-induced phosphorylation of c-Fos. The major phosphopeptides derived from biosynthetically labeled c-Fos correspond to phosphopeptides generated after phosphorylation of c-Fos in vitro with both RSK and MAP kinase. The phosphorylation sites identified for RSK (Ser-362) and MAP kinase (Ser-374) are in the transrepression ...
TY - JOUR. T1 - Epidermal Growth Factor-Activated Extracellular Signal-Regulated Kinase Suppresses Growth Hormone Expression and Stimulates Proliferation in MtT/E Cells. AU - Nogami, H.. AU - Soya, H.. AU - Hiraoka, Y.. AU - Aiso, Sadakazu. AU - Hisano, S.. PY - 2012/2/1. Y1 - 2012/2/1. N2 - The mechanism for the inhibition of growth hormone (GH) expression by the epidermal growth factor (EGF) was examined in two clonal cell lines, MtT/E and MtT/S. The former has a negligible basal level of GH, whereas the latter has a high basal GH. The treatment of MtT/E cells with retinoic acid resulted in a significant increase in GH mRNA and subsequently GH. This stimulatory response to retinoic acid was strongly suppressed by EGF. This suppression was associated with an increase in the phosphorylation of extracellular signal-regulated kinase 1 and 2 (Erk1/2). The MEK [mitogen-activated protein kinase (MAPK) kinases that activate ERK1 ...
Price for Single User $ 3080 USD :: MAP Kinase Interacting Serine/Threonine Protein Kinase 1 (MAP Kinase Signal Integrating Kinase 1 or MKNK1 or EC 2.7.11.1) - Pipeline Review, H2 2016SummaryGlobal Markets Directs, MAP Kinase Interacting Serine/Threonine Protein Kinase 1 (MAP Kinase
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This study uncovered a function of the dual specificity ERK MAP kinase phosphatase, MKP3, for the specification of mesenchymal progenitors in the somite sclerotome. We showed that Mkp3 was expressed in a twin-striped pattern, which closely matched the emergence of scleraxis transcripts along the anteroposterior somite edges (Fig. 1). This pattern suggested a link between the modulation of FGF signalling by MKP3 and scleraxis expression. We demonstrated that somitic expression of Mkp3 in the dorsal sclerotome was itself dependent on active ERK MAP kinase. This implied that FGF signalling in dorsal sclerotome cells is modulated by a negative feedback loop, which involves MKP3 and ERK MAP kinase. Indeed, we found that the levels of Mkp3 transcripts detected in response to FGF beads can cycle between extensive overexpression after a short exposure to complete loss of endogenous Mkp3 message after 24 hours (Fig. ...
Phosphoprotein signalling pathways have been intensively studied in vitro, yet their role in regulating tissue homeostasis is not fully understood. In the skin, interfollicular keratinocytes differentiate over approximately 2 weeks as they traverse the epidermis. The extracellular signal-regulated kinase (ERK) branch of the mitogen-activated protein kinase (MAPK) pathway has been implicated in this process. Therefore, we examined ERK-MAPK activity within human epidermal keratinocytes in situ. We used confocal microscopy and immunofluorescence labelling to measure the relative abundances of Raf-1, MEK1/2 and ERK1/2, and their phosphorylated (active) forms within three human skin samples. Additionally, we measured the abundance of selected proteins thought to modulate ERK-MAPK activity, including calmodulin, β1 integrin and stratifin (14-3-3σ); and of transcription factors known to act as effectors of ERK1/2, including the ...
A tetracycline-regulated reporter system was used to investigate the regulation of cyclooxygenase 2 (Cox-2) mRNA stability by the mitogen-activated protein kinase (MAPK) p38 signaling cascade. The stable beta-globin mRNA was rendered unstable by insertion of the 2, 500-nucleotide Cox-2 3 untranslated region (3 UTR). The chimeric transcript was stabilized by a constitutively active form of MAPK kinase 6, an activator of p38. This stabilization was blocked by SB203580, an inhibitor of p38, and by two different dominant negative forms of MAPK-activated protein kinase 2 (MAPKAPK-2), a kinase lying downstream of p38. Constitutively active MAPKAPK-2 was also able to stabilize chimeric beta-globin-Cox-2 transcripts. The MAPKAPK-2 substrate hsp27 may be involved in stabilization, as beta-globin-Cox-2 transcripts ...
MAPK signaling cascades seem to play divergent roles in the prostate gland. Significant differences have been observed in the activation pattern of all MAPK network components in prostate epithelial and stromal cells, under normal and pathologic conditions. Modulation of MAPK pathways has been shown in several prostate cancer cell lines by growth factors, cytokines, and a variety of agents that control growth and apoptosis of prostate cancer cells. However, structure and function of MAPK signal transduction pathways have not been thoroughly defined in prostate carcinogenesis.. The prostate is a heterogeneous gland comprising several cell types, which regulate each others function by paracrine mechanisms. Hence, it is important to decipher the role played by MAPK signal transduction pathways in mediating the interaction between various neighboring prostate cell types. A diverse array of ...
When contemplating how best to cripple this pathway, several key proteins are reasonable candidates for consideration. Most efforts to design small-molecule inhibitors of RAS-MAPK signaling have focused on the major protein players (i.e., RAS, RAF, MEK, and ERK). We may see more attention devoted in the future, however, to several scaffolding proteins and endogenous inhibitors that also come into play with respect to pathway dynamics (5). Recent advances in the development of genome-wide RNA interference libraries have enabled screening that may potentially identify other novel regulators of MAP signaling amenable to pharmacologic intervention (6, 7).. Is RAS druggable? Attempts to target RAS by perturbing its interaction with either SOS or GRB2 have not yielded viable drug development candidates largely because of the inherent difficulties of disrupting protein-protein interactions with drug-like molecules. Several drug discovery programs ...
Extracellular-signal-regulated kinases (ERKs), also called mitogen-activated protein kinases (MAPKs), are widely expressed signaling proteins that regulate meiosis, mitosis, and postmitotic functions in differentiated cells. Following activation by upstream kinases, ERKs are translocated to the nucleus, where they perform their regulatory functions. Disruption of ERK-mediated pathways is common in many cancers. Two members of this family were originally identified with 85% sequence similarity, called ERK1 and ERK2. ERK1 is also known as MAPK3, extracellular signal-regulated kinase 1, insulin-stimulated MAP2 kinase, microtubule-associated protein 2 kinase, PRKM3, ERT2, p44-ERK1, p44-MAPK, HS44KDAP, HUMKER1A, MAP kinase 1, and MAPK1. ERK2 is also known as ...
Extracellular-signal-regulated kinases (ERKs), also called mitogen-activated protein kinases (MAPKs), are widely expressed signaling proteins that regulate meiosis, mitosis, and postmitotic functions in differentiated cells. Following activation by upstream kinases, ERKs are translocated to the nucleus, where they perform their regulatory functions. Disruption of ERK-mediated pathways is common in many cancers. Two members of this family were originally identified with 85% sequence similarity, called ERK1 and ERK2. ERK1 is also known as MAPK3, extracellular signal-regulated kinase 1, insulin-stimulated MAP2 kinase, microtubule-associated protein 2 kinase, PRKM3, ERT2, p44-ERK1, p44-MAPK, HS44KDAP, HUMKER1A, MAP kinase 1, and MAPK1. ERK2 is also known as ...
TY - JOUR. T1 - Cell-cycle control linked to extracellular environment by MAP kinase pathway in fission yeast. AU - Shiozaki, Kazuhiro. AU - Russell, Paul. PY - 1995/12/14. Y1 - 1995/12/14. N2 - In fission yeast the onset of mitosis is brought about by Cdc2/Cdc13 kinase, which is inhibited by the Wee1/Mik1 tyrosine kinases and activated by Cdc25 tyrosine phosphatase. This control network integrates many signals, including those that monitor DNA replication, DNA damage and cell size. We report here that a fission yeast MAP kinase pathway links the cell-cycle G2/M control with changes in the extracellular environment that affect cell physiology. Fission yeast spc1- mutants have a G2 delay that is greatly exacerbated by growth in high osmolarity media and nutrient limitation. A lethal interaction of spc1 and cdc25 mutations shows that Spc1 promotes the onset of mitosis. Spc1 is a MAP ...
Cytolytic pore-forming toxins are important for the virulence of many disease-causing bacteria. How target cells molecularly respond to these toxins and whether or not they can mount a defense are poorly understood. By using microarrays, we demonstrate that the nematode Caenorhabditis elegans responds robustly to Cry5B, a member of the pore-forming Crystal toxin family made by Bacillus thuringiensis. This genomic response is distinct from that seen with a different stressor, the heavy metal cadmium. A p38 mitogen-activated protein kinase (MAPK) kinase and a c-Jun N-terminal-like MAPK are both transcriptionally up-regulated by Cry5B. Moreover, both MAPK pathways are functionally important because elimination of either leads to animals that are (i) hypersensitive to a low, chronic dose of toxin and (ii) hypersensitive to a high, brief dose of toxin such that the animal might naturally encounter in the wild. These results ...
A genetic screen for Caenorhabditis elegans mutants with enhanced susceptibility to killing by Pseudomonas aeruginosaled to the identification of two genes required for pathogen resistance: sek-1, which encodes a mitogen-activated protein (MAP) kinase kinase, and nsy-1, which encodes a MAP kinase kinase kinase. RNA interference assays and biochemical analysis established that a p38 ortholog, pmk-1, functions as the downstream MAP kinase required for pathogen defense. These data suggest that this MAP kinase signaling cassette represents an ancient feature of innate immune responses in evolutionarily diverse species. ...
TY - JOUR. T1 - Molecular cloning and characterization of mitogen-activated protein kinase 2 in Toxoplasma gondii. AU - Huang, Huan. AU - Ma, Yan Fen. AU - Bao, Yi. AU - Lee, Hattie. AU - Lisanti, Michael P.. AU - Tanowitz, Herbert B.. AU - Weiss, Louis M.. PY - 2011/10/31. Y1 - 2011/10/31. N2 - Mitogen-activated protein kinase (MAPK) pathways are major signal transduction systems by which eukaryotic cells convert environmental cues to intracellular events, such as cell proliferation and differentiation. Toxoplasma gondii is an obligate intracellular protozoan that is both a human and animal pathogen. This Apicomplexan causes significant morbidity and mortality in immune-competent and immune-compromised hosts. In humans, the most common manifestations of T. gondii infections are chorioretinitis in congenital infection and encephalitis in immune-compromised patients, such as patients with advanced AIDS. We have identified a ...
A diverse array of extracellular signals utilize MAP kinase signaling cascades to initiate a variety of cell signaling outcomes. The pleiotropic potential of MAP kinases emphasizes the importance of a tight control of their activation. In chromaffin cells (PC12) it was demonstrated that the duration of ERK activation by extracellular stimuli is critical for cell signaling outcomes, because transient activation of MAP kinase induced mitogenesis, whereas sustained activation of MAP kinase induced cell differentiation.27 28 However, in mesangial cells and fibroblasts, only potent mitogens seem to be capable of inducing a sustained phase of ERK activation.21 29 These data emphasize the importance of mechanisms to terminate and control the duration of ERK activity.. We19 20 and others11 have demonstrated previously that the ...
The mating response of the haploid yeast Saccharomyces cerevisiae provides a genetically tractable model system to study a G‐protein regulated mitogen‐activated protein (MAP) kinase cascade. This response is initiated by the pheromones a and α‐factor released from MATa and MATα cells, respectively. These short polypeptides bind to cell type‐specific receptors and thereby trigger the activation of a heterotrimeric G‐protein that is common to both cell types (for a review, see Herskowitz, 1995). The β and γ subunits of the G‐protein then activate a MAP kinase cascade consisting of Ste7p (a MAP kinase kinase or MEK homolog), Ste11p (a MEK kinase homolog) and the partially redundant MAP kinase homologs Fus3p and Kss1p (Herskowitz, 1995). The Ste20p protein kinase (a MEK kinase ...
Investigation of T-helper type 2 cytokines and the mitogen-activated protein kinase pathway in the modulation of bronchial hyperresponsiveness, airway inflammation and remodelling ...
The Raf-1 protein, encoded by the c-raf-1 gene, is a 75 kDa serine-threonine kinase that functions as a key regulator of cell growth, proliferation, and survival (1) . Raf-1 is a critical component of multiple signal transduction pathways, integrating signals from cell membrane-bound growth factor receptors and apoptotic regulators (2) . Activated Raf-1 in turn interfaces with a many downstream targets controlling proliferation and survival, including activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase kinases MEK1 and MEK2, activation of the nuclear factor κB survival and proliferation pathway, and inhibition of the proapoptotic factor Bad (3) .. Deregulated Raf-1 activity has been implicated in oncogenic transformation (4 , 5) . Constitutive Raf-1 activation leads to morphological changes consistent with a malignant phenotype, to growth factor-independent proliferation, and to increased resistance to ...
Catalytic domain of the dual-specificity Protein Kinase, MAP kinase kinase 7. Protein kinases (PKs), MAP kinase kinase 7 (MKK7) subfamily, catalytic (c) domain. PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. The MKK7 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. The mitogen-activated protein (MAP) kinase signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade ...
The HER-2 oncogene, a member of the erythroblastosis oncogene B (ERBB)-like oncogene family, has been shown to be amplified in many types of cancer, including breast cancer. However, the molecular mechanism of HER-2 overexpression is not completely understood. The phosphorylation of proteins on the serine or threonine residues that immediately precede proline (pSer/Thr-Pro) is specifically catalyzed by the prolyl isomerase Pin1 and is a key signaling mechanism in cell proliferation and transformation. Here, we found that Pin1 interacts with mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) protein kinase 1, resulting in the induction of HER-2 expression. Pin1−/− mouse embryonic fibroblasts exhibited a decrease in epidermal growth factor (EGF)-induced MEK1/2 phosphorylation compared with Pin1+/+ mouse embryonic fibroblast. In addition, a knockdown of Pin1 resulted in the inhibition of MEK1/2 ...
Mitogen-activated protein kinase (MAPK)-triggered protein kinase 2 (MAPKAPK2) mediates multiple p38 MAPK-dependent inflammatory responses. at Ser-58. Computational modeling and calculation of theoretical binding energies predicted that both phosphorylation at Ser-58 and mutation of Ser-58 to Asp (S58D) jeopardized the ability of 14-3-3 to dimerize. Experimentally, S58D mutation significantly impaired both 14-3-3 dimerization and binding to Raf-1. These data suggest that MAPKAPK2-mediated phosphorylation regulates 14-3-3 functions, and this MAPKAPK2 activity may symbolize a novel pathway mediating p38 MAPK-dependent swelling. A diverse group of cellular responses are elicited by activation of a highly conserved family of mitogen-activated protein kinase (MAPK) signaling pathways, which includes extracellular signal-regulated ...
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR). Ceramides are also able to activate MAP3K7/TAK1. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in ...
Phosphorylation and dephosphorylation events play an important role in the transmission of the ABA signal. Although SnRK2 [sucrose non-fermenting1-related kinase2] protein kinases and group A protein phosphatase type 2C (PP2C)-type phosphatases constitute the core ABA pathway, mitogen-activated protein kinase (MAPK) pathways are also involved in plant response to ABA. However, little is known about the interplay between MAPKs and PP2Cs or SnRK2 in the regulation of ABA pathways. In this study, an effort was made to elucidate the role of MAP kinase kinase kinase18 (MKKK18) in relation to ABA signaling and response. The MKKK18 knockout lines showed more vigorous root growth, decreased abaxial stomatal index and increased stomatal aperture under normal growth conditions, compared with the control wild-type Columbia line. In addition to ...
We have shown that contact with H. pylori rapidly activates ERK1, ERK2, p38, JNK p46, and JNK p54 MAP kinases in AGS gastric epithelial cells. We also find that H. pylori cag+ strains are more potent than cag− strains in inducing MAP kinase activation. Differential MAP kinase activation by cag+ and cag−H. pylori strains is particularly evident for JNK phosphorylation and appears to be dependent upon genes within the cag pathogenicity island. Inhibitors of p38 and MEK1 MAP kinases prevent H. pylori-induced IL-8 production. However, p38 and MEK1 MAP kinase activity do not appear to be essential for H. pylori-induced NF-κB activation.. H. pylori has adapted to interact specifically with gastric-type epithelial cells. H. pylori infection is limited to areas of the gastrointestinal tract that are lined by gastric epithelium, and the bacterium is ...
1. Raman M, Chen W, Cobb M.H. Differential regulation and properties of MAPKs. Oncogene. 2007;26(22):3100 2. Iñesta-Vaquera F, Sabio G, Kuma Y, Cuenda A. Alternative p38 Pathways MAPK. Stress-Activated Protein Kinases. Heidelberg: Springer Berlin. 2008:17 3. Adams R.H. et al. Essential role of p38alpha MAP kinase in placental but not embryonic cardiovascular development. Mol Cell. 2000;6(1):109 4. Allen M. et al. Deficiency of the stress kinase p38alpha results in embryonic lethality: characterization of the kinase dependence of stress responses of enzyme-deficient embryonic stem cells. J Exp Med. 2000;191(5):859 5. Mudgett J.S. et al. Essential role for p38alpha mitogen-activated protein kinase in placental angiogenesis. Proc Natl Acad Sci U S A. 2000;97(19):10454 6. Tamura K. et al. Requirement for p38alpha in erythropoietin expression: a role for stress ...
Catalytic domain of the Protein Serine/Threonine Kinase, MAP/ERK kinase kinase 3. Serine/threonine kinases (STKs), MAP/ERK kinase kinase 3 (MEKK3) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MEKK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. MEKK3 is a mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK or MKKK or MAP3K), that phosphorylates and activates the MAPK kinase MEK5 (or ...
The protein encoded by this gene is a serine/threonine kinase and is part of some signal transduction cascades, including the ERK and JNK kinase pathways as well as the NF-kappa-B pathway. The encoded protein is activated by autophosphorylation and requires magnesium as a cofactor in phosphorylating other proteins. This protein has E3 ligase activity conferred by a plant homeodomain (PHD) in its N-terminus and phospho-kinase activity conferred by a kinase domain in its C-terminus. [provided by RefSeq, Mar 2012 ...
Delayed cytoprotection (preconditioning) occurs 24h after sublethal simulated ischaemia and reperfusion (SI/R) in neonatal rat ventricular cardiomyocytes. SI/R was used to investigate the role of activation of mitogen-activated protein kinases (MAPKs), stress-activated protein kinases (SAPKs) and phosphoinositide 3-kinase-dependent protein kinase B (PKB)/Akt in cytoprotection. SI resulted in transient dual (Thr/Tyr) phosphorylation of p42/p44-MAPK and p38-MAPK, weak phosphorylation of p46/p54-SAPK, but no phosphorylation of PKB. Reperfusion caused further transient phosphorylation of p38-MAPK, but sustained phosphorylation of p42/p44-MAPK (lasting 4h) and of Ser473 of PKB (lasting 2h). Furthermore, SI/R (24h) induced delayed protection against lethal SI, as determined by an increase in cell viability {bioreduction of MTT ...
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This study is the first to demonstrate that reduced p27 expression is associated with acquired resistance to docetaxel in breast cancer cells in vitro. There may be several mechanisms that are involved in this process and that may be the result of either transcriptional or translational regulation, with modulation of gene expression and/or resultant production of the protein. In addition, there may be an increased degradation of p27 via the ubiquitin degradation pathway.. Previous studies have indicated that decreased expression of p27 is associated with drug resistance to hormonal therapy (e.g. tamoxifen) in breast cancer cells and to chemotherapy (e.g. cisplatin in malignant gliomas), mediated through mitogen-activated protein kinase activation [20, 21, 33]. It has also been reported that reduced p27 protein expression in epithelial ovarian tumours was observed, as compared with normal ovaries, from patients receiving cisplatin and paclitaxel treatment [34]. Reduced p27 expression was ...
Granulomatous nephritis can be triggered by diverse factors and results in kidney failure. However, despite accumulating data about granulomatous inflammation, pathogenetic mechanisms in nephritis remain unclear. The DNA-binding high-mobility group box-1 protein (HMGB1) initiates and propagates inflammation when released by activated macrophages, and functions as an alarm cytokine signaling tissue damage. In this study, we showed elevated HMGB1 expression in renal granulomas in rats with crystal-induced granulomatous nephritis caused by feeding an adenine-rich diet. HMGB1 levels were also raised in urine and serum, as well as in monocyte chemoattractant protein-1 (MCP-1), a mediator of granulomatous inflammation. Injection of HMGB1 worsened renal function and upregulated MCP-1 in rats with crystal-induced granulomatous nephritis. HMGB1 also induced MCP-1 secretion through mitogen-activated protein kinase (MAPK) and phosphoinositide-3-kinase ...
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0004] BRAF is a member of the Raf kinase family of serine/threonine-specific protein kinases. BRAF plays an important role in regulating the MAPK/ERK signaling pathway, which affects cell division, proliferation, differentiation, and secretion. The RAS/RAF/MEK/ERK pathway acts as a signal transducer to send extracellular signals such as hormones, cytokines, and various growth factors into cell nucleus, directing a range of biochemical and physiological processes including cell differentiation, proliferation, growth, and apoptosis (McCubrey, J. A., et al., Biochim. Biophys. Acta, 2007, 1773 (8): 1263-84). The RAS/RAF/MEK/ERK pathway is frequently mutated in many human cancers (Downward, J., Nat. Rev. Cancer, 2003, 3 (1): 11-22). The finding that mutations in BRAF caused a wide range of human cancers and many of these tumors are dependent on the constitutive activation of BRAF/MEK/ERK pathway fueled drug discovery efforts in searching for ...
The protein encoded by this gene is a member of the dual specificity protein kinase family, which acts 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 kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon wide variety of extra- and intracellular signals. As an essential component of MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development ...
Activation of Ras-MAPK signalling pathway is predominantly essential for promoting neuronal cell growth and differentiation. [21]Several pathways derive from Trk receptors for activation of Ras molecules, which begin by formation of ligand-bound mitogen (BDNF or NGF) at an extracellular domain of the trk, causing receptor dimerization. This subsequently will lead to phosphorylation of the intracellular parts of the receptors, which activates Guanine Exchange factors (GEFs), such as sos, Grb2 and Shc. GEFs trigger the exchange of GDP bound to inactive Ras to GTP, resulting Ras to activate. The presence of activated Ras molecules, stimulate signaling via a major downstream pathway known as MAP kinase (mitogen-activated protein kinase)-although activated Ras, would be also capable of triggering several other downstream pathways such as PLC-y1 and PI3-kinases (Figure..). [21] Mitogen-activated protein ...
Activation of Ras-MAPK signalling pathway is predominantly essential for promoting neuronal cell growth and differentiation. [19]Several pathways derive from Trk receptors for activation of Ras molecules, which begin by formation of ligand-bound mitogen (BDNF or NGF) at an extracellular domain of the trk, causing receptor dimerization. This subsequently will lead to phosphorylation of the intracellular parts of the receptors, which activates Guanine Exchange factors (GEFs), such as sos, Grb2 and Shc. GEFs trigger the exchange of GDP bound to inactive Ras to GTP, resulting Ras to activate. The presence of activated Ras molecules, stimulate signaling via a major downstream pathway known as MAP kinase (mitogen-activated protein kinase)-although activated Ras, would be also capable of triggering several other downstream pathways such as PLC-y1 and PI3-kinases (Figure..). [19] Mitogen-activated protein ...
The phosphorylation of the human estrogen receptor (ER) serine residue at position 118 is required for full activity of the ER activation function 1 (AF-1). This Ser118 is phosphorylated by mitogen-activated protein kinase (MAPK) in vitro and in cells treated with epidermal growth factor (EGF) and insulin-like growth factor (IGF) in vivo. Overexpression of MAPK kinase (MAPKK) or of the guanine nucleotide binding protein Ras, both of which activate MAPK, enhanced estrogen-induced and antiestrogen (tamoxifen)-induced transcriptional activity of wild-type ER, but not that of a mutant ER with an alanine in place of Ser118. Thus, the activity of the amino-terminal AF-1 of the ER is modulated by the phosphorylation of Ser118 through the Ras-MAPK cascade of the growth factor signaling pathways.. ...
Cancer cells have different characteristics due to the genetic differences where these unique features may strongly influence the effectiveness of therapeutic interventions. Here, we show that the spontaneous reactivation of extracellular signal-regulated kinase (ERK), distinct from conventional ERK activation, represents a potent mechanism for cancer cell survival. We studied ERK1/2 activation in vitro in SW480 colorectal cancer cells. Although ERK signaling tends to be transiently activated, we observed the delayed reactivation of ERK1/2 in epidermal growth factor (EGF)-stimulated SW480 cells. This effect was observed even after EGF withdrawal. While phosphorylated ERK1/2 translocated into the nucleus following its primary activation, it remained in the cytoplasm during late-phase activation. The inhibition of primary ERK1/2 activation or protein trafficking, blocked reactivation and concurrently increased caspase 3 activity. Our results suggest that the biphasic ...
Cerebral ischemia is associated with the activation of glial cells, infiltration of leukocytes and an increase in inflammatory mediators in the ischemic brain and systemic circulation. How this inflammatory response influences lesion size and neurological outcome remains unclear. D-JNKI1, an inhibitor of the c-Jun N-terminal kinase pathway, is strongly neuroprotective in animal models of stroke. Intriguingly, the protection mediated by D-JNKI1 is high even with intravenous administration at very low doses with undetectable drug levels in the brain, pointing to a systemic mode of action, perhaps on inflammation. We evaluated whether D-JNKI1, administered intravenously 3 h after the onset of middle cerebral artery occlusion (MCAO), modulates secretion of the inflammatory mediators interleukin-6 and keratinocyte-derived chemokine in the plasma and from the spleen and brain at several time points after MCAO. We found an early release of both mediators in the ...
We have recently reported that activation of the Raf-1/mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase 1/2 (MEK1/2)/ERK1/2 signaling cascade in gastrointestinal carcinoid cell line (BON) alters cellular morphology and neuroendocrine phenotype. The mechanisms by which Raf-1 mediates these changes in carcinoid cells are unclear. Here, we report that activation of the Raf-1 signaling cascade in BON cells induced the expression of focal adhesion kinase (FAK) protein, suppressed the production of neuroendocrine markers, and resulted in significant decreases in cellular adhesion and migration. Importantly, inactivation of MEK1/2 by 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene or abolition of FAK induction in Raf-1-activated BON cells by targeted siRNA led to reversal of the Raf-1-mediated reduction in neuroendocrine markers and cellular adhesion and migration. ...
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 itself is dependent on the Ser/Thr phosphorylation by MAP kinase kinase kinases. The inhibition or degradation of this kinase is found to be involved in the pathogenesis of Yersinia and anthrax. ...
ALK_HUMAN] Neuronal orphan receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system. Transduces signals from ligands at the cell surface, through specific activation of the mitogen-activated protein kinase (MAPK) pathway. Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif. Following activation by ligand, ALK induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Acts as a receptor for ligands pleiotrophin (PTN), a secreted growth factor, and midkine (MDK), a PTN-related factor, thus participating in PTN and MDK signal transduction. PTN-binding induces MAPK pathway ...
Haq R, Shoag J, Andreu-Perez P, Yokoyama S, Edelman H, Rowe GC, Fredericket DT, et al. Oncogenic BRAF regulates oxidative metabolism via PGC1α and MITF. Cancer Cell 2013 March 18 [Epub ahead of print].. BRAF mutations are common in melanoma and are most often represented by the V600E mutation, which results in constitutive activation of its serine/threonine kinase activity, with downstream effects on the mitogen-activated protein kinase (MAPK) signal transduction pathway. The BRAF inhibitor vemurafenib (PLX4032) is effective in patients with the V600E mutation, and the presence of the BRAFV600E allele is used clinically as a predictive marker to select patients for this therapy. Although tumor regression after vemurafenib is often seen with BRAF-mutant melanomas, relapse and tumor resistance are common within months of treatment. How BRAF-mutant melanomas grow even under conditions of nutrient scarcity is not well understood. The Warburg effect (preferential ...
MAPK3 [ENSP00000263025]. Extracellular signal-regulated kinase 1; Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 ...
The regulation of protein phosphorylation requires a balance in the activity of protein kinases and protein phosphatases. Our previous data indicates that Src can increase ERK activity through Raf kinase in response to ischemic stimuli. This study examined the molecular mechanisms by which Src activates ERK cascade through protein phosphatases following cerebral ischemia. Ischemia-induced Src activation is followed by phosphorylation of PP2A at Tyr307 leading to its inhibition in the rat hippocampus. SU6656, a Src inhibitor, up-regulates PP2A activity, resulting in a significant decreased activity in ERK and its targets, CREB and ERα. In addition, the PP2A inhibitor, cantharidin, led to an up-regulation of ERK activity and was able to counteract Src inhibition during ischemia. Src induces up-regulation of ERK activity and its target transcription factors, CREB and ERα, through attenuation of PP2A activity. Therefore, activation of ERK is the result of a crosstalk between two ...
Cytoplasmic Janus protein tyrosine kinases (JAKs) are crucial components of diverse signal transduction pathways that govern cellular survival, proliferation, differentiation and apoptosis. Evidence to date, indicates that JAK kinase function may integrate components of diverse signaling cascades. While it is likely that activation of STAT proteins may be an important function attributed to the JAK kinases, it is certainly not the only function performed by this key family of cytoplasmic tyrosine kinases. Emerging evidence indicates that phosphorylation of cytokine and growth factor receptors may be the primary functional attribute of JAK kinases. The JAK-triggered receptor phosphorylation can potentially be a rate-limiting event for a successful culmination of downstream signaling events. In support of this hypothesis, it has been found that JAK kinase function is required ...
The transcription factor nuclear factor (NF)-κB plays a pivotal role in the regulation of innate immunity, stress responses, inflammation, and the inhibition of apoptosis 1,2. The activity of NF-κB is tightly regulated by cytokines and other external stimuli. In most cell types, NF-κB is present as a heterodimer comprising 50-kD (p50) and 65-kD (p65) subunits and is sequestered in the cytoplasm by a member of the inhibitor of κB (IκB) family of inhibitory proteins. NF-κB activation requires the degradation of IκB proteins, and the mechanisms of IκB degradation and subsequent NF-κB activation have been the subject of intense investigation 3. Those studies have revealed two important classes of kinase involved in this pathway: mitogen-activated protein kinase kinase kinase (MAP3K) and its downstream target, IκB kinase (IKK) 4,5. NF-κB-inducing kinase (NIK) is structurally related to ...
Melanomas are well known to be "addicted" to signaling through the Ras/Raf/MEK/ERK MAPK pathway, with the majority of melanoma driver oncogenes reported thus far known to activate this signal transduction cascade. Even among those melanomas lacking the obvious MAPK pathway activators such as oncogenic BRAF and NRAS, constitutive levels of MEK/ERK signaling are still required. It therefore comes as little surprise that melanomas possess multiple means to reactivate MAPK signaling and that many of the acquired BRAF inhibitor resistance mechanisms reported so far, including most of those that have been convincingly validated in clinical specimens, are MAPK dependent. The fact that near total MAPK pathway blockade is required for BRAF inhibitor efficacy in patients with melanoma suggests that even modest increases in the level of signaling through the ...
We have demonstrated that in the H526 SCLC cell line, Lck activity is required for SCF-stimulated MAPK activation using two complementary techniques: (a) although activation of both Kit and MAPK were sensitive to inhibition by the tyrosine kinase inhibitor PP1, MAPK inhibition occurred at a lower PP1 concentration; this greater sensitivity to PP1 could be partially reversed by overexpression of Lck; and (b) inducible expression of a kinase-inactive DN Lck protein blocked SCF-mediated MAPK activation in a dose-dependent fashion. Although these observations run contrary to the dogma that receptor tyrosine kinases activate the Ras-MAPK pathway directly, they are consistent with a large body of data that demonstrates the importance of Src kinases in signaling from class-III RTKs, including the PDGFR, CSF-1R, and Kit. In murine fibroblasts ...
TY - JOUR. T1 - Heat shock-induced activation of stress MAP kinase is regulated by threonine-and tyrosine-specific phosphatases. AU - Nguyen, Aaron Ngocky. AU - Shiozaki, Kazuhiro. PY - 1999/7/1. Y1 - 1999/7/1. N2 - In eukaryotic species from yeast to human, stress-activated protein kinases (SAPKs), members of a MAP kinase (MAPK) subfamily, regulate the transcriptional response to various environmental stress. It is poorly understood how diverse forms of stress are sensed and transmitted to SAPKs. Here, we report the heat shock regulation of the fission yeast Spc1 SAPK, a homolog of human p38 and budding yeast Hog1p. Although osmostress and oxidative stress induce strong activation of the Wis1 MAPK kinase (MEK), which activates Spc1 through Thr-171/Tyr-173 phosphorylation, activation of Wis1 upon heat shock is relatively weak and transient. However, in heat- shocked cells, ...
Purpose : Protein kinases play an important role in several cell processes such as proliferation, transcription, and pathologic changes. Kinase inhibitors have thus been proposed for treatment against diseases including cancer. In ophthalmology, ROCK inhibitor has already been launched as an antiglaucoma drug in Japan. However, discovery of small molecule inhibitors for specific protein kinases is still challenging. This is because approximately 500 protein kinases exist and more than 2,000 other purine-binding proteins share similar ATP binding pockets of kinases. The purpose of this study was to develop an in silico method for identifying potential kinase inhibitors, and the anticancer drug axitinib was used as a representative kinase inhibitor. Methods : Sequences for 9 typical kinases were compared to VEGFR tyrosine kinase, the three amino acid sequences ...
Janus kinase (JAK) is a family of intracellular, nonreceptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway. They were initially named "just another kinase" 1 and 2 (since they were just two of a large number of discoveries in a PCR-based screen of kinases,) but were ultimately published as "Janus kinase". The name is taken from the two-faced Roman god of beginnings and endings, Janus, because the JAKs possess two near-identical phosphate-transferring domains. One domain exhibits the kinase activity, while the other negatively regulates the kinase activity of the first. The four JAK family members are: Janus kinase 1 (JAK1) Janus kinase 2 (JAK2) Janus kinase 3 (JAK3) Tyrosine kinase 2 (TYK2) Transgenic mice that do not express JAK1 have defective responses to some cytokines, such as ...
SB203580 is a pyridinyl imidazole inhibitor widely used to elucidate the roles of p38 mitogen-activated protein (MAP) kinase.. SB203580 inhibits also the phosphorylation and activation of protein kinase B (PKB, also known as Akt). Both kinases are involved in a wide array of signaling pathways, including the TLR signaling pathway. Moreover, several studies suggest that p38 MAPKs regulate distinct phases of autophagy. p38 can elicit autophagy via Beclin1. Contrarily, p38α has also been reported to inhibit autophagy by interfering with the trafficking of Atg9.
Activation of p38 mitogen-activated protein kinase (MAPK) is known to be important in cytokine production and cell survival in inflammation. This study examined the effect of inhibiting p38 MAPK after onset of renal injury in an experimental model of crescentic glomerulonephritis. Furthermore, this study investigated whether p38 MAPK inhibition would cause widespread suppression of the cytokine network in vivo or uncontrolled apoptosis. In the in vivo studies, daily treatment with a p38 MAPKalpha/beta inhibitor was started 1 h (early treatment study) or 4 d (late treatment study) after induction of nephrotoxic nephritis in Wistar Kyoto rats. The treated rats remained healthy with normal weight gain during the study. Both early and late treatment with p38 MAPK inhibitor reduced renal monocyte chemoattractant protein-1 (MCP-1) levels, the number of glomerular macrophages, the severity of tissue injury, and ...
The mitogen-activated protein kinase (MAPK) pathway is the canonical signaling pathway for many receptor tyrosine kinases, such as the Epidermal Growth Factor Receptor. Downstream of the receptors, this pathway involves the activation of a kinase cascade that culminates in a transcriptional response and affects processes, such as cell migration and adhesion. In addition, the strength and duration of the upstream signal also influence the mode of the cellular response that is switched on. Thus, the same components can in principle coordinate opposite responses, such as proliferation and differentiation. In recent years, it has become evident that MAPK signaling is regulated and fine-tuned by proteins that can bind to several MAPK signaling proteins simultaneously and, thereby, affect their function. These so-called MAPK scaffolding proteins ...
Abstract: : Purpose: Previous studies from our laboratory have shown ET-1 treatment promotes apoptosis of cultured rat retinal ganglion cells. The purpose of this study was to determine if p38 MAP kinase is involved in ET-1 mediated apoptosis of retinal ganglion cells. Methods: Virally transformed rat retinal ganglion cells (RGC5) were treated with 100nM ET-1 for 5, 10 and 15 min. Activation of p38 MAP Kinase was determined by immunoblotting using anti phospho p38 antibody. p38 MAP kinase assay was carried out using ATF-2 as substrate in the presence of γ 32P. In addition, the kinase assay samples were separated by SDS /PAGE (10%) and radioactivity incorporated into ATF2 was detected by autoradiography. Results: An increase in p38 phosphorylation was observed following ET-1 (100nM) treatment for 5 min in RGC5 cells, which was restored to near control levels by 10 min. A corresponding ...
Rabbit polyclonal BCKDH kinase antibody validated for WB, IHC and tested in Human and Mouse. Referenced in 1 publication. Immunogen corresponding to…
MEK1 is a member of the MAPK signal transduction pathway that responds to growth factors and cytokines. We have determined that the kinase domain spans residue 35 to 382 by proteolytic cleavage. The complete kinase domain has been crystallized and its X-ray crystal structure as a complex with magnesium and ATP-S determined at 2.1 ?. Unlike crystals of a truncated kinase domain previously published, the crystals of the intact domain can be grown either as a binary complex with a nucleotide or a ternary complex with a nucleotide and one of a multitude of allosteric inhibitors. Further the crystals allow for the determination of co-structures with ATP competitive inhibitors. We describe the structures of non-phosphorylated MEK1 (npMEK1) binary complexes with ADP, and K252a, an ATP-competitive inhibitor (see table 1) at 1.9 ?, and 2.7 ? resolution, respectively. Ternary complexes have also been solved between npMEK1, a nucleotide and an ...
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 protein is a neuronal-specific form of c-Jun N-terminal kinases (JNKs). Through its phosphorylation and nuclear localization, this kinase plays regulatory roles in the signaling pathways during neuronal apoptosis. Beta-arrestin 2, a receptor-regulated MAP kinase scaffold protein, is found to interact with, and stimulate the phosphorylation of this kinase by MAP kinase kinase 4 (MKK4). Cyclin-dependent kinase 5 can phosphorylate, and inhibit the activity of this kinase, which ...
MAPKs function as the terminal components of three-tiered cascades of kinases comprised of a MAPK kinase kinase (MAP3K), MAPK kinase (MAP2K), and MAPK and are important signal transducers in development, homeostasis, and disease (Chang and Karin, 2001). For example, the p38 subfamily of MAPKs is involved in a wide variety of biological processes, including inflammation, stress responses, and cell differentiation (Zarubin and Han, 2005). The myriad roles of MAPK cascades indicate that the specificity of MAPK activation and function must be regulated. One mechanism by which this occurs is via MAPK scaffold proteins, which are thought to provide (1) specificity between distinct MAPK subfamilies by assembling individual MAPK ...
A series of 3-(4-fluorophenyl)-2-(4-pyridyl)-chromone derivs. were synthesized and evaluated as p38 MAP kinase inhibitors. Introduction of an amino group in the 2-position of the pyridyl moiety gave p38 inhibitors with IC50 values in the low nanomolar range (e.g. 8a; IC50 = 17 nm). Addnl., the inhibitors (8a and 8e) demonstrate an excellent selectivity profile towards the p38 kinase among other kinases, as well as inhibition (8e) of p38 signaling in human breast cancer cells. [on SciFinder(R)]. ...
Figure 2: Examples of the probability distribution (a, b, and c) and trace plots (d, e, and f) of reaction rates 2 (which indicates the simultaneous recruitment of Shc and Grb2-SOS complex from the cytosol to the cell membrane by the recruitment of EGFR (a and d)), 16 (which shows the activation of MEK proteins by active Raf (b and e)), and 38 (which refers to the dissociation of active ERK and RSK complex (c and f)) of Model 2 under ...
Our protein biology products such as Peptide Synthesis and Elisa Kits allow you to detect, measure, and explore a protein expressions identity and function

Chemical and Synthetic Biology Approaches to Understand Cellular Functions - Part A, Volume 621 - 1st EditionChemical and Synthetic Biology Approaches to Understand Cellular Functions - Part A, Volume 621 - 1st Edition

A mass spectrometry-based isotope-coded mass tag method to map thiol accessibility in biological systems. John E. Gadbery and ... 8. Methods for the recombinant expression of active tyrosine kinase domains: Guidelines and pitfalls. M. Escarlet Díaz Galicia ... Shuklas laboratory is focused on understanding the molecular mechanism of activation, signaling and regulation of G Protein- ... information on methods to measure ubiquitin chain length and linkage and genetic approaches to study the yeast ubiquitin system ...
more infohttps://www.elsevier.com/books/chemical-and-synthetic-biology-approaches-to-understand-cellular-functions-part-a/shukla/978-0-12-818117-1

MAP Kinase Signaling System | Profiles RNSMAP Kinase Signaling System | Profiles RNS

MAP Kinase Signaling System. *Mechanotransduction, Cellular. *Second Messenger Systems. *Synaptic Transmission. *Wnt Signaling ... "MAP Kinase Signaling System" by people in this website by year, and whether "MAP Kinase Signaling System" was a major or minor ... "MAP Kinase Signaling System".. *Biological Sciences [G]. *Chemical Phenomena [G02]. *Biochemical Phenomena [G02.111] ... An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream ...
more infohttps://profiles.umassmed.edu/display/105851

Genes Regulated in Metastatic Osteosarcoma: Evaluation by Microarray Analysis in Four Human and Two Mouse Cell Line SystemsGenes Regulated in Metastatic Osteosarcoma: Evaluation by Microarray Analysis in Four Human and Two Mouse Cell Line Systems

Genes involved in ERK1 and -2 kinase, MAP kinase, SMAD, and TGFβ signaling and in ureteric bud, prostate gland, blood vessel ... system and the MG63/M8 system obtained by in vitro selection of M8 from MG63. Clustering of the two mouse systems with distinct ... The greatest variability was observed in the term "biological process." Here, enrichment was observed in all cell systems in ... and K12/K7M2 systems and at intermediate levels in the HOS/143B system. In the MG63/M8 system it was upregulated 4-fold from ...
more infohttps://www.hindawi.com/journals/sarcoma/2012/937506/

Two-dimensional parameter scan of MKKK and MKK-P partic | Open-iTwo-dimensional parameter scan of MKKK and MKK-P partic | Open-i

... covariance in the ERK MAP model. A two-dimensional parameter scan of the covariance of the pa ... MAP Kinase Signaling System. *Models, Biological. *Software. *Stochastic Processes. *p38 Mitogen-Activated Protein Kinases/ ... Affiliation: School of Computer Science and Manchester Centre for Integrative Systems Biology, The University of Manchester, ... signalling -- one generic model of extracellular signal-regulated kinases (ERK) and one model of signalling via p38 MAPK.We ...
more infohttps://openi.nlm.nih.gov/detailedresult.php?img=PMC3814289_1752-0509-6-86-4&req=4

MAP Kinase Signaling System | Profiles RNSMAP Kinase Signaling System | Profiles RNS

MAP Kinase Signaling System. *Mechanotransduction, Cellular. *Second Messenger Systems. *Synaptic Transmission. *Wnt Signaling ... "MAP Kinase Signaling System" by people in this website by year, and whether "MAP Kinase Signaling System" was a major or minor ... "MAP Kinase Signaling System".. *Biological Sciences [G]. *Chemical Phenomena [G02]. *Biochemical Phenomena [G02.111] ... An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream ...
more infohttps://profiles.uchicago.edu/profiles/display/31604

A Conserved p38 MAP Kinase Pathway in Caenorhabditis elegans Innate Immunity | ScienceA Conserved p38 MAP Kinase Pathway in Caenorhabditis elegans Innate Immunity | Science

... biochemical and cell biological studies in mammalian systems have implicated a critical role for p38 MAP kinase signaling in ... species may yield key insights into the evolutionary origins and molecular mechanisms of the mammalian innate immune system (1 ... MAP kinase kinases specifically activate the p38 family of MAP kinases and MKK4 MAP kinase kinase can activate p38 MAP kinase ... MAP) kinase kinase, and nsy-1, which encodes a MAP kinase kinase kinase. RNA interference assays and biochemical analysis ...
more infohttps://science.sciencemag.org/content/297/5581/623?ijkey=e68dfd6d5b6a46599cd5e4261b66ba5bce6a229a&keytype2=tf_ipsecsha

NASA - NanoRacks-The Investigation of Countermeasures to Modulate and Augment the Immune SystemNASA - NanoRacks-The Investigation of Countermeasures to Modulate and Augment the Immune System

... the effects of radiation exposure to the signal transduction pathway on mitogen-activated protein (MAP) kinases that regulate ... IEEE Aerospace and Electronic Systems Magazine. 2009 July; 28(4): 85-90. DOI: 10.1109/MEMB.2009.933572. Marriott KC, Bartee R, ... a. Determine the local radiation environment for the ISS biological experiment(s) which gives investigators information that ... Zwieb C, Bhuiyan S. Archaea Signal Recognition Particle Shows the Way. Archaea. 2010; 2010: 1-11. DOI: 10.1155/2010/485051. ...
more infohttps://www.nasa.gov/mission_pages/station/research/experiments/1246.html

Systematic discovery of linear binding motifs targeting an ancient protein interaction surface on MAP kinases | Molecular...Systematic discovery of linear binding motifs targeting an ancient protein interaction surface on MAP kinases | Molecular...

... based systems will greatly contribute to a system‐level understanding of protein kinase‐based intracellular signaling networks. ... Lee KS, Park J‐E, Kang YH, Kim T‐S, Bang JK (2014) Mechanisms underlying Plk1 polo‐box domain‐mediated biological processes and ... dependent kinase/MAPK/glycogen synthase kinase 3/CDK‐like) kinase group. However, each kinase family uses a different surface, ... While extracellularly regulated kinases (ERK1‐2), c‐Jun N‐terminal kinases (JNK1‐3), and the 38‐kDa protein kinases (p38α‐δ) ...
more infohttp://msb.embopress.org/content/11/11/837

Mathematical Representations of Cell Biological Systems II - Mathematical Representations of Cell Biological Systems |...Mathematical Representations of Cell Biological Systems II - Mathematical Representations of Cell Biological Systems |...

Introduction to Systems Biology. Module description goes here. Learn online and earn valuable credentials from top ... MEK to activate MAP kinase and these two reactions occur in the cytoplasm. ... In contrast, stochastic systems require that the progress of the system is determined by predictable Both by the predictable ... These systems underlie core subcellular processes such as signal transduction, transcription, motility and electrical ...
more infohttps://www.coursera.org/lecture/systems-biology/mathematical-representations-of-cell-biological-systems-ii-yBbAt

Center for Theoretical & Mathematical Sciences   » PeopleCenter for Theoretical & Mathematical Sciences » People

MAP Kinase Signaling System • Mathematics • Medial Forebrain Bundle • Melanins • Metabolic Detoxication, Drug • Metabolic ... Biological Evolution • Biological Markers • Biological Transport • Biomass • Biometry • Body Constitution • Body Patterning • ... Anderson, DF; Mattingly, JC; Nijhout, HF; Reed, MC, Propagation of fluctuations in biochemical systems, I: Linear SSC networks ... Wheeler, DE; Nijhout, HF, A perspective for understanding the modes of juvenile hormone action as a lipid signaling system., ...
more infohttp://fds.duke.edu/db/aas/math/ctms/faculty/hfn

Systems biology approaches in cell signaling research | Genome Biology | Full TextSystems biology approaches in cell signaling research | Genome Biology | Full Text

Recent studies reveal important information about the rates of signal transmission and propagation, help establish some general ... regulatory characteristics of multi-tiered signaling cascades, and illuminate the combinatorial nature of signaling specificity ... The use of methods for global and quantitative analysis of cells is providing new systems-level insights into signal ... 13] showed that the concentration of MAP kinase phosphatase is crucial for determining whether MAP kinase signaling in NIH-3T3 ...
more infohttps://genomebiology.biomedcentral.com/articles/10.1186/gb-2005-6-10-235

Browsing UT Southwestern Electronic Theses and Dissertations by Subject MAP Kinase Signaling SystemBrowsing UT Southwestern Electronic Theses and Dissertations by Subject "MAP Kinase Signaling System"

One of the major functions of kinases in biological systems is the relay of signal from an effector to a downstream target. ... Browsing UT Southwestern Electronic Theses and Dissertations by Subject "MAP Kinase Signaling System". 0-9. A. B. C. D. E. F. G ... The RAF/MEK/MAP Kinase signal transduction cascade is the most extensively studied MAPK pathway that mediates diverse cellular ... Kinases are regulated by a diversity of mechanisms, both internal and external to the kinase. When ... ...
more infohttp://repositories.tdl.org/utswmed-ir/handle/2152.5/203/browse?value=MAP+Kinase+Signaling+System&type=subject

Publications - Labnodes - The Vanderbilt Research NetworkPublications - Labnodes - The Vanderbilt Research Network

MAP Kinase Signaling System, Male, Mice, Mice, Inbred C57BL, Models, Biological, Osteoblasts, Phosphatidylinositol 3-Kinases, ... METHODS - Recombinant FXI variants lacking one or both ABSs were tested in polyP-dependent purified protein systems, plasma ... p38 MAP kinases, MEK1, cPLA₂, and src tyrosine kinase-dependent manner (28.1 ± 2.3 pg/2 × 10⁸ platelets). Unlike free PGs, they ... MAP Kinase Kinase 1, Phosphatidylethanolamines, Phospholipids, Platelet Activation, Prostaglandin D2, Prostaglandins, Protein ...
more infohttps://labnodes.vanderbilt.edu/publication/search?filter%5Bsearch%5D%5Bquery%5D=Thrombin&filter%5Bsearch%5D%5Bfields%5D%5B%5D=mesh_terms

Books by Subject - Lane Medical Library - Stanford University School of MedicineBooks by Subject - Lane Medical Library - Stanford University School of Medicine

A microinjectable biological system, the Xenopus oocyte, as an approach to understanding signal transduction protein function ... Combining microinjection and immunoblotting to analyse MAP kinase phosphorylation in single starfish oocytes and eggs / David J ... P signalling and recognition systems / Marc Lenoir and Michael Overduin -- PtdIns(4,5)P2-mediated cell signaling: emerging ... Cell signaling networks are complex dynamical systems with mechanisms for adaptation and failure-tolerance such that typical ...
more infohttp://lane.stanford.edu/biomed-resources/ebsubjectbrowse.html?m=Cell%20Biology&page=3

Integrative Genomic Approaches to Identify Biomarkers and Therapeutic… - EnglishIntegrative Genomic Approaches to Identify Biomarkers and Therapeutic… - English

... system development MPNST ‣ Apoptosis ‣ Negative regulation of MAP kinase activity ‣ Phosphoinositide- mediated signaling ‣ ... Study: Biological pathways that drive NF1 tumor progression Research objectives: 1. Gain insight into the biological pathways ... system development MPNST ‣ Apoptosis ‣ Negative regulation of MAP kinase activity ‣ Phosphoinositide- mediated signaling ‣ ... Nervous system development Shared activation Apoptosis Cell cycle control Cell proliferation Regulation of MAP kinase activity ...
more infohttps://www.slideshare.net/wjjessen/covance-talk

The Biological Effects of Weak Electromagnetic Fields - Problems and solutionsThe Biological Effects of Weak Electromagnetic Fields - Problems and solutions

... including the MAP-kinase cascades, which amplify the signal. If the damage is not too severe or prolonged, we see a stimulation ... Leakage of the cells of the peripheral nervous system in adults makes them send false signals to the brain, which results in ... electrochemical gradient to affect calcium-sensitive enzyme systems. This is the normal mechanism by which cells sense ... Bron: www.foodsmatter.com/es/health_risks/articles/goldsworthy-biological-effects-04-12.pdf maart 2012 Andrew Goldsworthy ...
more infohttps://stopumts.nl/doc.php/Onderzoeken/9577/the_biological_effects_of_weak_electromagnetic_fields_-_problems_and_solutions

Protocols and Video Articles Authored by Megan  N. McClean (Translated to Norwegian)Protocols and Video Articles Authored by Megan N. McClean (Translated to Norwegian)

Signal Processing by the HOG MAP Kinase Pathway Proceedings of the National Academy of Sciences of the United States of America ... used in our study are general and can be applied to understanding other signaling pathways in a range of biological systems. ... The system is based on the chimeric transcriptional activator Gal4dbd.ER.VP16 (GEV). Upon addition of the hormone β-estradiol ... We recently used such an approach to measure the signal processing behavior of the budding yeast HOG MAP kinase pathway in ...
more infohttps://www.jove.com/author/Megan++N._McClean?language=Norwegian

Mathematical model of TGF-βsignalling: feedback coupling is consistent with signal switching | BMC Systems Biology | Full TextMathematical model of TGF-βsignalling: feedback coupling is consistent with signal switching | BMC Systems Biology | Full Text

Although TGF-β signalling can be complex, many of the signalling components are well defined, so it is possible to develop ... We developed our mathematical model for the TGF-β signalling pathway, i.e. the RF- model of TGF-β signalling, using the ... In conjunction with other oncogenic changes, long-term perturbation of TGF-β signalling is associated with cancer metastasis. ... The parameterization of our TGF-β signalling model is consistent with experimental data. ...
more infohttps://bmcsystbiol.biomedcentral.com/articles/10.1186/s12918-017-0421-5

Frontiers | Modeling Drug- and Chemical-Induced Hepatotoxicity with Systems Biology Approaches | PhysiologyFrontiers | Modeling Drug- and Chemical-Induced Hepatotoxicity with Systems Biology Approaches | Physiology

We provide an overview of computational systems biology approaches as applied to the study of chemical- and drug-induced ... We provide an overview of computational systems biology approaches as applied to the study of chemical- and drug-induced ... MAP kinase phosphatase as a locus of flexibility in a mitogen-activated protein kinase signaling network. Science 297, 1018- ... 2010). A system-level investigation into the cellular toxic response mechanism mediated by AhR signal transduction pathway. ...
more infohttps://www.frontiersin.org/articles/10.3389/fphys.2012.00462/full

The slipper snail, Crepidula: an Emerging lophotrochozoan model system[dagger]. - Free Online LibraryThe slipper snail, Crepidula: an Emerging lophotrochozoan model system[dagger]. - Free Online Library

The Biological Bulletin; Biological sciences Animal development Models Research Developmental biology Evolutionary biology ... an Emerging lophotrochozoan model system[dagger].(Report) by ... Dimerization in MAP-kinase signaling. Trends Biochem. Sci. 25: ... partly due to the lack of well-developed model systems. Molluscs are one of the most diverse lophotrochozoan phyla, with over ... Mitogen-activated protein kinases (MAPK, or extracellular signal-related kinases, ERK) are conserved serine/threonine kinases ...
more infohttps://www.thefreelibrary.com/The+slipper+snail%2C+Crepidula%3A+an+Emerging+lophotrochozoan+model+...-a0232076667

Ultrasensitivity - WikipediaUltrasensitivity - Wikipedia

"Using Engineered Scaffold Interactions to Reshape MAP Kinase Pathway Signaling Dynamics". Science. 319 (5869): 1539-43. Bibcode ... and implicated the importance of this in many biological systems. Many biological processes are binary (ON-OFF), such as cell ... This is especially relevant for large cascades, such as the flagellar regulatory system in which the master regulator signal is ... In mitogen-activated protein kinase (MAPK) signaling (see example below), the ultrasensitivity of the signaling is supported by ...
more infohttps://en.wikipedia.org/wiki/Ultrasensitivity

TENM1 - Teneurin-1 - Homo sapiens (Human) - TENM1 gene & proteinTENM1 - Teneurin-1 - Homo sapiens (Human) - TENM1 gene & protein

May function as a cellular signal transducer (By similarity). ... establishment of proper connectivity within the nervous system ... Activates the mitogen-activated protein (MAP) kinase 2 (MEK2) and extracellular signal-regulated kinase (ERK) cascade. Acts ... nervous system development Source: ProtInc ,p>Traceable Author Statement,/p> ,p>Used for information from review articles where ... Biological process. Stress response, Transcription, Transcription regulation. Enzyme and pathway databases. SignaLink: a ...
more infohttp://www.uniprot.org/uniprot/Q9UKZ4

RECOMB Regulatory Genomics / Systems Biology / DREAM Conference 2010 | The New York Academy of SciencesRECOMB Regulatory Genomics / Systems Biology / DREAM Conference 2010 | The New York Academy of Sciences

... in regulatory genomics and systems biology to discuss latest findings and establish new collaborations towards a systems-level ... in contrast to more familiar ErbB signaling, raising FGF19 turns off β-catenin without activating MAP kinase. "In liver cancer ... Dissecting Wnt signaling. Biological signaling defines the biological context within which genetic programs are executed. In ... In modeling this system, Julio Saez-Rodriguez assembled a consensus network from information in the literature and then refined ...
more infohttps://www.nyas.org/ebriefings/recomb-regulatory-genomics-systems-biology-dream-conference-2010/

Type Inference in Systems Biology | SpringerLinkType Inference in Systems Biology | SpringerLink

Scaffold proteins biphasically affect the levels of mitogen-activated protein kinase signaling and reduce its threshold ... Kohn, K.W.: Molecular interaction map of the mammalian cell cycle control and DNA repair systems. Molecular Biology of the Cell ... System Biology Reaction Model Type System Abstract Interpretation Type Inference These keywords were added by machine and not ... Journal of Biological Physics and Chemistry 4, 64-73 (2004)CrossRefGoogle Scholar ...
more infohttps://link.springer.com/chapter/10.1007/11885191_4

PD Dr. Stephan Seiler - Freiburg Institute for Advanced Studies - FRIASPD Dr. Stephan Seiler - Freiburg Institute for Advanced Studies - FRIAS

... understanding pulsatile MAK2 MAP kinase signaling in Neurospora. Communication among microbes is a fundamental biological ... Filamentous fungi that secrete a vast array of metabolites and putative signaling molecules are excellent model systems to ... connection between chemical gradient sensing and regulation of cell polarity is only poorly understood in any eukaryotic system ... The NDR kinase scaffold HYM1/MO25 is essential for MAK2 MAP kinase signaling in Neurospora crassa. PLOS Genetics, 8:e1002950. ...
more infohttp://www.frias.uni-freiburg.de/en/people/fellows/current-fellows/seiler
  • NanoRacks-The Investigation of Countermeasures to Modulate and Augment the Immune System (NanoRacks-ISS University Research (UR) - 1) begins with the development and refinement of a synthetic pathway for efficient production of synthetic benzofuran-2-carboxylic acid derivatives on the ground. (nasa.gov)
  • And in this type of model eh, a, a typical example is for the MAPK signaling pathway. (coursera.org)
  • Quantitative analysis is increasingly being used to discover the general principles relating the functional properties of a signaling pathway to its basic topological characteristics. (biomedcentral.com)
  • Signal Processing by the HOG MAP Kinase Pathway Proceedings of the National Academy of Sciences of the United States of America. (jove.com)
  • We developed our mathematical model for the TGF- β signalling pathway, i.e. the RF- model of TGF- β signalling, using the "rapid equilibrium assumption" to reduce the network of TGF- β signalling reactions based on the time scales of the individual reactions. (biomedcentral.com)
  • Pathway mapping and modeling based on network biology concepts are a key component of the vision laid out in this report for a more biologically based analysis of dose-response behavior and the safety of chemicals and drugs. (frontiersin.org)
  • Stochastic fluctuations in molecular numbers have been in many cases shown to be crucial for the understanding of biochemical systems. (nih.gov)
  • NanoRacks-The Investigation of Countermeasures to Modulate and Augment the Immune System (NanoRacks-ISS University Research (UR) - 1) is contributory toward the development of solutions to immune system and radiation risks that have plagued NASA and its crew members for years and includes the study of the effects of radiation and microgravity in these phenomena since they are the most significant impediments to humans on long term exploration missions. (nasa.gov)
  • In the same sense, a major goal of current research is to collect information and devise tools to help us understand biological phenomena at multiple levels of abstraction. (biomedcentral.com)
  • Most of them involve the inward leakage of free calcium ions down an enormous electrochemical gradient to affect calcium-sensitive enzyme systems. (stopumts.nl)
  • Using two osteoblastic cell line systems, the most common OS phenotype, we have identified forty-eight common genes that are differentially expressed in metastatic cell lines compared to parental cells. (hindawi.com)
  • An optimized protocol to quantify signaling in human transitional B cells by phospho flow cytometry. (uchicago.edu)
  • NanoRacks-The Investigation of Countermeasures to Modulate and Augment the Immune System (NanoRacks-ISS University Research (UR)-1) studies a chemical compound that fights some of these ill effects by enhancing immune cells. (nasa.gov)
  • Indeed, lactoferrin exerts its biological effects by binding to specific lactoferrin receptors on target cells. (stanford.edu)
  • Leakage of the cells of the peripheral nervous system in adults makes them send false signals to the brain, which results in the symptoms of electromagnetic intolerance (aka electromagnetic hypersensitivity). (stopumts.nl)
  • Signalling feedback loops are required to model TGF-β signal transduction and its effects on normal and cancer cells. (biomedcentral.com)
  • The results from the RF- model compare well with experimental data and predict the dynamics of TGF-β signalling in cancer cells with different mutations. (biomedcentral.com)
  • This acts to filter out noise, as small stimuli and threshold concentrations of the stimulus (input signal) is necessary for the trigger which allows the system to get activated quickly. (wikipedia.org)
  • The most useful road maps are those that provide an overview of the major highways, as well as displaying street-by-street detail for specific locations to reveal the connections at points of interest. (biomedcentral.com)
  • The development of experimental host-pathogen systems that use invertebrate hosts greatly facilitates the genetic analysis of immune function of a host organism. (sciencemag.org)
  • This book also covers the in-depth information on roles of lactoferrin as a signaling molecule. (stanford.edu)
  • The model initially focuses on reactive metabolite-induced DILI in response to administration of acetaminophen, and spans multiple biological scales. (frontiersin.org)
  • Here, we have analyzed by microarray the differential gene expression in four human and two mouse OS cell line systems consisting of parental cell lines with low metastatic potential and derivatives thereof with increased metastatic potential. (hindawi.com)
  • To our knowledge, four human and two mouse OS systems were developed that fulfill this requirement. (hindawi.com)
  • Microgravity and radiation exposure in space suppress human immune systems. (nasa.gov)
  • The disordered part of the human proteome contains a large number of short linear motif occurrences that can bind to MAP kinases. (embopress.org)
  • Transforming growth factor β (TGF- β ) signalling regulates the development of embryos and tissue homeostasis in adults. (biomedcentral.com)
  • Ultrasensitivity gives a small response to first input signal, but an increase in the input signal produces higher and higher levels of output. (wikipedia.org)
  • Successive cascade signals can result in higher levels of noise being introduced into the signal that can interfere with the final output. (wikipedia.org)
  • We focus on the effects of time-delayed feedback loops and their coupling to ligand stimulation in this system. (biomedcentral.com)
  • Design og implementering av en automatisert Illuminating, dyrking, og Sampling System for Microbial optogenetic Applications Cameron J. Stewart 1 , Megan N. McClean 1 1 Department of Biomedical Engineering, University of Wisconsin-Madison Vi har konstruert en kontinuerlig dyrkingsapparat for bruk med optogenetic systemer for å belyse kulturer av mikrober og regelmessig bildet celler i avløpet med et invertert mikroskop. (jove.com)