Dual-Specificity Phosphatases: A sub-class of protein tyrosine phosphatases that contain an additional phosphatase activity which cleaves phosphate ester bonds on SERINE or THREONINE residues that are located on the same protein.Dual Specificity Phosphatase 3: A dual specificity phosphatase subtype that plays a role in intracellular signal transduction by inactivating MITOGEN-ACTIVATED PROTEIN KINASES. It has specificity for EXTRACELLULAR SIGNAL-REGULATED MAP KINASES.Dual Specificity Phosphatase 6: A dual specificity phosphatase subtype that plays a role in intracellular signal transduction by inactivating MITOGEN-ACTIVATED PROTEIN KINASES. It has specificity for EXTRACELLULAR SIGNAL-REGULATED MAP KINASES and is primarily localized to the CYTOSOL.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.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.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.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 Tyrosine Phosphatases: An enzyme group that specifically dephosphorylates phosphotyrosyl residues in selected proteins. Together with PROTEIN-TYROSINE KINASE, it regulates tyrosine phosphorylation and dephosphorylation in cellular signal transduction and may play a role in cell growth control and carcinogenesis.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)Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.cdc25 Phosphatases: A subclass of dual specificity phosphatases that play a role in the progression of the CELL CYCLE. They dephosphorylate and activate CYCLIN-DEPENDENT KINASES.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.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Protein Tyrosine Phosphatases, Non-Receptor: A subcategory of protein tyrosine phosphatases that occur in the CYTOPLASM. Many of the proteins in this category play a role in intracellular signal transduction.Phosphoric Monoester Hydrolases: A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. EC 3.1.3.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Dual Specificity Phosphatase 2: A dual specificity phosphatase subtype that plays a role in intracellular signal transduction by inactivating MITOGEN-ACTIVATED PROTEIN KINASES. It has specificity for EXTRACELLULAR SIGNAL-REGULATED MAP KINASES and is primarily localized to the CELL NUCLEUS.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.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.Lafora Disease: A form of stimulus sensitive myoclonic epilepsy inherited as an autosomal recessive condition. The most common presenting feature is a single seizure in the second decade of life. This is followed by progressive myoclonus, myoclonic seizures, tonic-clonic seizures, focal occipital seizures, intellectual decline, and severe motor and coordination impairments. Most affected individuals do not live past the age of 25 years. Concentric amyloid (Lafora) bodies are found in neurons, liver, skin, bone, and muscle (From Menkes, Textbook of Childhood Neurology, 5th ed, pp111-110)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.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.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.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).Mitogen-Activated Protein Kinase 1: A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.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.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.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.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.Sensitivity and Specificity: Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)Immediate-Early Proteins: Proteins that are coded by immediate-early genes, in the absence of de novo protein synthesis. The term was originally used exclusively for viral regulatory proteins that were synthesized just after viral integration into the host cell. It is also used to describe cellular proteins which are synthesized immediately after the resting cell is stimulated by extracellular signals.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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.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.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.COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Cell Line, Tumor: A cell line derived from cultured tumor cells.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.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.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.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.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Protein Phosphatase 2: A phosphoprotein phosphatase subtype that is comprised of a catalytic subunit and two different regulatory subunits. At least two genes encode isoforms of the protein phosphatase catalytic subunit, while several isoforms of regulatory subunits exist due to the presence of multiple genes and the alternative splicing of their mRNAs. Protein phosphatase 2 acts on a broad variety of cellular proteins and may play a role as a regulator of intracellular signaling processes.Acid Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 18.104.22.168.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.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.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.Kinetics: The rate dynamics in chemical or physical systems.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)Recombinant Proteins: Proteins prepared by recombinant DNA technology.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.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.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.Antibody Specificity: The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.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.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.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.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.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.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.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 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.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.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.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 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.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.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.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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.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.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.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.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.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).Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.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.Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.Glucose-6-Phosphatase: An enzyme that catalyzes the conversion of D-glucose 6-phosphate and water to D-glucose and orthophosphate. EC 22.214.171.124.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)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.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.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.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.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.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Mice, Inbred C57BLProto-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.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.Glutathione Transferase: A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite.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.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.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.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.Species Specificity: The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.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.Blotting, Northern: Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.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.Cercopithecus aethiops: A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.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.Antibodies, Bispecific: Antibodies, often monoclonal, in which the two antigen-binding sites are specific for separate ANTIGENIC DETERMINANTS. They are artificial antibodies produced by chemical crosslinking, fusion of HYBRIDOMA cells, or by molecular genetic techniques. They function as the main mediators of targeted cellular cytotoxicity and have been shown to be efficient in the targeting of drugs, toxins, radiolabeled haptens, and effector cells to diseased tissue, primarily tumors.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Bromodeoxyuridine: A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors.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.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.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).Cytoplasm: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)Gene Library: A large collection of DNA fragments cloned (CLONING, MOLECULAR) from a given organism, tissue, organ, or cell type. It may contain complete genomic sequences (GENOMIC LIBRARY) or complementary DNA sequences, the latter being formed from messenger RNA and lacking intron sequences.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.Lymphocyte Activation: Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.PhosphoproteinsT-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.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).Okadaic Acid: A specific inhibitor of phosphoserine/threonine protein phosphatase 1 and 2a. It is also a potent tumor promoter. (Thromb Res 1992;67(4):345-54 & Cancer Res 1993;53(2):239-41)Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Protein Tyrosine Phosphatase, Non-Receptor Type 11: A subtype of non-receptor protein tyrosine phosphatases that contain two SRC HOMOLOGY DOMAINS. Mutations in the gene for protein tyrosine phosphatase, non-receptor type 11 are associated with NOONAN SYNDROME.Protein Tyrosine Phosphatase, Non-Receptor Type 1: A subtype of non-receptor protein tyrosine phosphatases that includes two distinctive targeting motifs; an N-terminal motif specific for the INSULIN RECEPTOR, and a C-terminal motif specific for the SH3 domain containing proteins. This subtype includes a hydrophobic domain which localizes it to the ENDOPLASMIC RETICULUM.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.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a CONSENSUS SEQUENCE. AMINO ACID MOTIFS are often composed of conserved sequences.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Epithelial Cells: Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.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.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.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.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.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.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.Transcriptional Activation: Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.Mice, Inbred BALB CProliferating Cell Nuclear Antigen: Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Phosphotransferases (Alcohol Group Acceptor): A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.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.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.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Protein Tyrosine Phosphatase, Non-Receptor Type 6: A Src-homology domain-containing protein tyrosine phosphatase found in the CYTOSOL of hematopoietic cells. It plays a role in signal transduction by dephosphorylating signaling proteins that are activated or inactivated by PROTEIN-TYROSINE KINASES.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.Cyclin-Dependent Kinase Inhibitor p27: A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.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.Mice, Nude: Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Mitosis: A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.Cell Growth Processes: Processes required for CELL ENLARGEMENT and CELL PROLIFERATION.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.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.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.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.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.Ki-67 Antigen: A CELL CYCLE and tumor growth marker which can be readily detected using IMMUNOCYTOCHEMISTRY methods. Ki-67 is a nuclear antigen present only in the nuclei of cycling cells.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 126.96.36.199.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Myosin-Light-Chain Phosphatase: A phosphoprotein phosphatase that is specific for MYOSIN LIGHT CHAINS. It is composed of three subunits, which include a catalytic subunit, a myosin binding subunit, and a third subunit of unknown function.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.Muscle, Smooth, Vascular: The nonstriated involuntary muscle tissue of blood vessels.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Cell Transformation, Neoplastic: Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.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.Cell Adhesion: Adherence of cells to surfaces or to other cells.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Organ Specificity: Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen.Stem Cells: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.ThymidineThymidine 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 188.8.131.52.Molecular Weight: The sum of the weight of all the atoms in a molecule.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.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Cyclin-Dependent Kinase Inhibitor p21: A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.Tumor Suppressor Proteins: Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.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.Gene Expression Regulation, Developmental: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.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.Gene Knockdown Techniques: The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.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.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.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 enzymesTetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Phosphorylase Phosphatase: An enzyme that deactivates glycogen phosphorylase a by releasing inorganic phosphate and phosphorylase b, the inactive form. EC 184.108.40.206.
"Diverse physiological functions for dual-specificity MAP kinase phosphatases". J Cell Sci. pp. 4607-4615. doi:10.1242/jcs.03266 ... This can involve gene regulation, cell proliferation, programmed cell death and stress responses. MAPK phosphatases are ... "Diverse physiological functions for dual-specificity MAP kinase phosphatases". J Cell Sci. pp. 4607-4615. doi:10.1242/jcs.03266 ... The newest MKP-8 brings the total MKPs to 11, MKP-8 plays a role in inhibiting p38 kinase. Dual specificity phosphatases (DUSPs ...
... pTyr-specific phosphatases dual specificity phosphatases (dTyr and dSer/dThr) Cdc25 phosphatases (dTyr and/or dThr) LMW (low ... and cell cycle control, and are important in the control of cell growth, proliferation, differentiation and transformation. The ... "The nonreceptor protein tyrosine phosphatase corkscrew functions in multiple receptor tyrosine kinase pathways in Drosophila". ... Paul S, Lombroso PJ (November 2003). "Receptor and nonreceptor protein tyrosine phosphatases in the nervous system". Cell. Mol ...
Members of the protein tyrosine phosphatase superfamily cooperate with protein kinases to regulate cell proliferation and ... a testis-specific dual specificity protein phosphatase: implications for substrate specificity". Proteins. 66 (1): 239-45. doi: ... One family, the dual specificity phosphatases (DSPs) acts on both phosphotyrosine and phosphoserine/threonine residues. This ... Dual specificity phosphatase 13 is an enzyme that in humans is encoded by the DUSP13 gene. ...
Cyclin-dependent kinase 2
Hannon GJ, Casso D, Beach D (March 1994). "KAP: a dual specificity phosphatase that interacts with cyclin-dependent kinases". ... "C/EBPalpha arrests cell proliferation through direct inhibition of Cdk2 and Cdk4". Mol. Cell. 8 (4): 817-28. doi:10.1016/s1097- ... Cyclin-dependent kinase 2, also known as cell division protein kinase 2, is an enzyme that in humans is encoded by the CDK2 ... "The structural basis for specificity of substrate and recruitment peptides for cyclin-dependent kinases". Nat. Cell Biol. 1 (7 ...
Protein tyrosine phosphatase
Dual-specificity protein phosphatases (DSPs) regulate mitogenic signal transduction and control the cell cycle. LEOPARD ... proliferation, differentiation, transformation, and synaptic plasticity. Together with tyrosine kinases, PTPs regulate the ... dual-specificity protein-tyrosine phosphatases. Ser/Thr and Tyr dual-specificity phosphatases are a group of enzymes with both ... Yuvaniyama J, Denu JM, Dixon JE, Saper MA (May 1996). "Crystal structure of the dual specificity protein phosphatase VHR". ...
Together, kinases and phosphatases direct a form of post-translational modification that is essential to the cell's regulatory ... Similarly, dual-specificity tyrosine phosphatases can dephosphorylate not only tyrosine residues, but also serine residues. ... PP2B, also called calcineurin, is involved in the proliferation of T cells; because of this, it is the target of some drugs ... Acid phosphatase Alkaline phosphatase Endonuclease/Exonuclease/phosphatase family Kinase Phosphatome Phosphotransferase Protein ...
Mitogenom-aktivirana proteinska kinaza 1 - Википедија, слободна енциклопедија
2008). „Dual-specificity phosphatase 1 ubiquitination in extracellular signal-regulated kinase-mediated control of growth in ... 1999). „Inhibition of T cell signaling by mitogen-activated protein kinase-targeted hematopoietic tyrosine phosphatase (HePTP ... promotes functional cooperation of Bcl2 and c-Myc through phosphorylation in regulating cell survival and proliferation". J. ... 2001). „Molecular cloning and characterization of a novel dual specificity phosphatase, LMW-DSP2, that lacks the cdc25 homology ...
... cell proliferation, differentiation, cell cycle arrest, and apoptosis. For full activation of MAPKs, dual-specificity kinases ... DUSP16 dual specificity phosphatase 16". Tanoue, T; Yamamoto T; Maeda R; Nishida E (Jul 2001). "A Novel MAPK phosphatase MKP-7 ... Dual specificity protein phosphatase 16 is an enzyme that in humans is encoded by the DUSP16 gene. The activation of mitogen- ... MKPs are dual-specificity phosphatases that dephosphorylate the TXY motif, thereby negatively regulating MAPK activity.[ ...
... protein tyrosine kinases and protein serine/threonine kinases. Dual-specificity kinases are subclass of the tyrosine kinases. ... It inhibits T-cell proliferation and proliferative responses induced by several cytokines, including interleukin 1 (IL-1), IL-2 ... Tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a negative regulator of PI3K signaling. In ... mTOR is a kinase within the family of phosphatidylinositol-3 kinase-related kinases (PIKKs), which is a family of serine/ ...
Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases ... In melanocytic cells DUSP4 gene expression may be regulated by MITF. GRCh38: Ensembl release 89: ENSG00000120875 - Ensembl, May ... which are associated with cellular proliferation and differentiation. ... The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases ...
"Crosstalk between cAMP-dependent kinase and MAP kinase through a protein tyrosine phosphatase". Nat. Cell Biol. 1 (5): 305-11. ... kinase phosphatase-3 N-terminal noncatalytic region is responsible for tight substrate binding and enzymatic specificity". J. ... act in a signaling cascade that regulates various cellular processes such as proliferation, differentiation, and cell cycle ... "Inhibition of T cell signaling by mitogen-activated protein kinase-targeted hematopoietic tyrosine phosphatase (HePTP)". J. ...
"Control of dual-specificity phosphatase-1 expression in activated macrophages by IL-10". European Journal of Immunology. 35 (10 ... It also enhances B cell survival, proliferation, and antibody production. IL-10 can block NF-κB activity, and is involved in ... CD28-associated IL-10 receptor inhibits CD28 tyrosine phosphorylation and phosphatidylinositol 3-kinase binding". FASEB Journal ... mast cells, CD4+CD25+Foxp3+ regulatory T cells, and in a certain subset of activated T cells and B cells. IL-10 can be produced ...
... protein tyrosine phosphatases (PTP), and dual-specificity phosphatases (DUSP). For example, ser/thr phosphatases PP2Cα/β ... "Selective suppression of stress-activated protein kinase pathway by protein phosphatase 2C in mammalian cells". FEBS Letters. ... p38α MAPK is implicated in cell survival/apoptosis, proliferation, differentiation, migration, mRNA stability, and inflammatory ... Tanoue T, Moriguchi T, Nishida E (Jul 1999). "Molecular cloning and characterization of a novel dual specificity phosphatase, ...
"Syk is a dual-specificity kinase that self-regulates the signal output from the B-cell antigen receptor". Proceedings of the ... "The B cell receptor promotes B cell activation and proliferation through a non-ITAM tyrosine in the Igalpha cytoplasmic domain ... of the tyrosine phosphatase PTP1C as a B cell antigen receptor-associated protein involved in the regulation of B cell ... Because even on B-cell precursors, it can be used to stain a wider range of cells than can the alternative B-cell marker CD20, ...
Mitogen-activated protein kinase
Similarly, both dual-specificity MAP kinase phosphatases and MAP-specific tyrosine phosphatases bind to MAP kinases through the ... The latter phosphorylate a number of substrates important for cell proliferation, cell cycle progression, cell division and ... Signal transduction MAP kinase kinase MAP kinase kinase kinase MAP kinase kinase kinase kinase MAPK1 (ERK2) MAPK3 (ERK1) MAPK7 ... A very conserved family of dedicated phosphatases is the so-called MAP kinase phosphatases (MKPs), a subgroup of dual- ...
Hannon, G J; Casso D; Beach D (Mar 1994). "KAP: a dual specificity phosphatase that interacts with cyclin-dependent kinases". ... 2001). "C/EBPalpha arrests cell proliferation through direct inhibition of Cdk2 and Cdk4". Mol. Cell. 8 (4): 817-28. doi: ... Hannon GJ, Casso D, Beach D (1994). "KAP: a dual specificity phosphatase that interacts with cyclin-dependent kinases". Proc. ... "Entrez Gene: CDKN3 cyclin-dependent kinase inhibitor 3 (CDK2-associated dual specificity phosphatase)". Yeh, Chau-Ting; Lu Su- ...
2003). "Dual-specificity phosphatase Pyst2-L is constitutively highly expressed in myeloid leukemia and other malignant cells ... 1996). "Differential regulation of the MAP, SAP and RK/p38 kinases by Pyst1, a novel cytosolic dual-specificity phosphatase". ... MAPK activation cascades mediate various physiologic processes, including cellular proliferation, apoptosis, differentiation, ... Dual specificity protein phosphatase 7 is an enzyme that in humans is encoded by the DUSP7 gene. Dual-specificity phosphatases ...
Giembycz MA (June 2005). "Life after PDE4: overcoming adverse events with dual-specificity phosphodiesterase inhibitors". Curr ... In intact cells, PDE1 is almost exclusively activated by Ca2+ entering the cell from the extracellular space. The regulation of ... Phosphorylation of PDE1A1 and PDE1A2 by protein kinase A and of PDE1B1 by CaM Kinase II decreases their sensitivity to ... PDE1C has been shown to be a major regulator of smooth muscle proliferation, at least in human smooth muscle. Nonproliferating ...
Studies of the mouse counterpart of this gene suggested that this kinase play a key role in T cell proliferation, apoptosis and ... Tanoue T, Moriguchi T, Nishida E (July 1999). "Molecular cloning and characterization of a novel dual specificity phosphatase, ... "Molecular cloning and characterization of a novel dual specificity phosphatase, LMW-DSP2, that lacks the cdc25 homology domain ... c-Jun N-terminal kinase (JNK) kinase 2, and JNK1 results in efficient and specific JNK1 activation". Mol. Cell. Biol. 20 (7): ...
Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases ... Alonso A, Saxena M, Williams S, Mustelin T (2001). "Inhibitory role for dual specificity phosphatase VHR in T cell antigen ... which are associated with cellular proliferation and differentiation. ... "Entrez Gene: DUSP3 dual specificity phosphatase 3 (vaccinia virus phosphatase VH1-related)". "DEXA data for Dusp3". Wellcome ...
"Dual-specificity phosphatase 1 ubiquitination in extracellular signal-regulated kinase-mediated control of growth in human ... "Inhibition of T cell signaling by mitogen-activated protein kinase-targeted hematopoietic tyrosine phosphatase (HePTP)". J. ... promotes functional cooperation of Bcl2 and c-Myc through phosphorylation in regulating cell survival and proliferation". J. ... The activation of this kinase requires its phosphorylation by upstream kinases. Upon activation, this kinase translocates to ...
Cdk2, la enciclopedia libre
de 1994). «KAP: a dual specificity phosphatase that interacts with cyclin-dependent kinases». Proc. Natl. Acad. Sci. U.S.A. ( ... de 2001). «C/EBPalpha arrests cell proliferation through direct inhibition of Cdk2 and Cdk4». Mol. Cell (United States) 8 (4): ... de 1999). «The structural basis for specificity of substrate and recruitment peptides for cyclin-dependent kinases». Nat. Cell ... de 1999). «BRCA1 is phosphorylated at serine 1497 in vivo at a cyclin-dependent kinase 2 phosphorylation site». Mol. Cell. Biol ...
The cell polarity protein kinase Pom1, a member of the dual-specificity tyrosine-phosphorylation regulated kinase (DYRK) family ... referred to as proliferation, where a cell, known as the "mother cell", grows and divides to produce two "daughter cells" (M ... When cells have reached sufficient size during G2, the phosphatase Cdc25 removes the inhibitory phosphorylation, and thus ... A cell is unable to grow to an abnormally large size because at a certain cell size or cell mass, the S phase is initiated. The ...
Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases ... "Multiple dual specificity protein tyrosine phosphatases are expressed and regulated differentially in liver cell lines". The ... which are associated with cellular proliferation and differentiation. ... The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases ...
Serine/threonine-specific protein kinase
Serine/Threonine Kinase receptors play a role in the regulation of cell proliferation, programmed cell death (apoptosis), cell ... see serine/threonine-specific protein kinases. 2.7.12: protein-dual-specificity. *see serine/threonine-specific protein kinases ... protein tyrosine phosphatase: Receptor-like protein tyrosine phosphatase. *Sh2 domain-containing protein tyrosine phosphatase ... All three Akt kinases regulate cell proliferation and Akt2 is particularly important for insulin actions in cells. A major ...
"Dual-specificity phosphatase 1 ubiquitination in extracellular signal-regulated kinase-mediated control of growth in human ... Progression through the cell cycle is tightly regulated by cyclin-dependent kinases (CDKs), and their interactions with cyclins ... which will inhibit aberrant cellular proliferation. Although Skp2 is an enzyme, its function requires the assembly of the other ... Nakayama KI, Nakayama K (June 2005). "Regulation of the cell cycle by SCF-type ubiquitin ligases". Seminars in Cell & ...
Many Ser/Thr and dual-specificity protein kinases are important for signal transduction, either acting downstream of [receptor ... These molecular events are the basic mechanisms controlling cell growth, proliferation, metabolism and many other processes. In ... examples include tyrosine kinase and phosphatases. Often such enzymes are covalently linked to the receptor. Some of them ... Integrins are produced by a wide variety of cells; they play a role in cell attachment to other cells and the extracellular ...
... is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo". Cell. 75 (3): 487-93. doi:10.1016/0092-8674(93) ... role in the human cellular response to environmental stress as well as in the negative regulation of cellular proliferation. ... dual-specificity protein tyrosine phosphatases". Molecules and Cells. 8 (1): 2-11. PMID 9571625. Keyse SM (Apr 1998). "Protein ... which encodes a dual specificity (Tyr/Thr) MAP kinase phosphatase, is highly conserved and maps to human chromosome 5q34". ...
Dual specificity protein phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and ... Martell KJ, Angelotti T, Ullrich A (1998). "The "VH1-like" dual-specificity protein tyrosine phosphatases". Mol. Cells. 8 (1): ... which is associated with cellular proliferation and differentiation. Different members of this family of dual specificity ... "Entrez Gene: DUSP10 dual specificity phosphatase 10". Tanoue, T; Moriguchi T; Nishida E (Jul 1999). "Molecular cloning and ...
MKP1 | definition of MKP1 by Medical dictionary
A gene on chromosome 5q34 that encodes dual-specificity phosphatase 1, a protein which dephosphorylates MAP kinase MAPK1/ERK2. ... DUSP1 downregulates cell proliferation and is thought to play a key role in cellular responses to environmental stress. It is ... The phosphatase MKP1 is a transcriptional target of p53 involved in cell cycle regulation.. Exit from arsenite-induced mitotic ...
MAPK phosphatase - Wikipedia
"Diverse physiological functions for dual-specificity MAP kinase phosphatases". J Cell Sci. pp. 4607-4615. doi:10.1242/jcs.03266 ... This can involve gene regulation, cell proliferation, programmed cell death and stress responses. MAPK phosphatases are ... "Diverse physiological functions for dual-specificity MAP kinase phosphatases". J Cell Sci. pp. 4607-4615. doi:10.1242/jcs.03266 ... The newest MKP-8 brings the total MKPs to 11, MKP-8 plays a role in inhibiting p38 kinase. Dual specificity phosphatases (DUSPs ...
Dual specificity phosphatase, catalytic domain (IPR000340) | InterPro | EMBL-EBI
... and cell cycle control, and are important in the control of cell growth, proliferation, differentiation and transformation [ ... including a number of enzymes which have been phosphorylated under the action of a kinase. Dual specificity protein ... This entry represents dual specificity protein-tyrosine phosphatases. Ser/Thr and Tyr dual specificity phosphatases are a group ... Dual specificity phosphatase, catalytic domain (IPR000340). Short name: Dual-sp_phosphatase_cat-dom ...
Altered Gene Expression Profiles Define Pathways in Colorectal Cancer Cell Lines Affected by Celecoxib | Cancer Epidemiology,...
CDC25A is a dual specificity phosphatase that regulates cell cycle transitions at the G1-S and G2-M entry points (28-31). ... were identified that are directly or indirectly involved in cell proliferation and survival. CDC2 is a cyclin-dependent kinase ... In all four cell lines, cell cycle/cell proliferation, DNA replication, DNA metabolism, DNA repair, and response to DNA damage ... Arsenite slows S phase progression via inhibition of cdc25A dual specificity phosphatase gene transcription. Toxicol Sci 2007; ...
Estrogen-related receptor α regulates skeletal myocyte differentiation via modulation of the ERK MAP kinase pathway | Cell...
Dual-specificity phosphatases: critical regulators with diverse cellular targets. Biochem J 418: 475-489, 2009. ... Critical proliferation-independent window for basic fibroblast growth factor repression of myogenesis via the p42/p44 MAPK ... MEK/ERK inactivation in early myogenesis is mediated by the dual-specificity phosphatase MKP-1. In WT primary myocytes we ... Subtype specific roles of mitogen activated protein kinases in L6E9 skeletal muscle cell differentiation. Mol Cell Biochem 238 ...
... a kinase upstream of Erk) reverses hypoxia protective effect on ErbB2-expressing cells. One potential mechanism of how hypoxia/ ... a transcription factor that regulates cell growth, proliferation and survival. As a result, hypoxic tumors are often ... Breast cancer ErbB2-positive patients are treated with lapatinib, a dual EGFR/ERBB2 inhibitor. Despite lapatinib clinical ... Here we demonstrate that cells exposed to hypoxia have decreased levels of DUSP2 and it correlate with increased activation of ...
phosphatase Inhibition | phosphatase Inhibitor Review
Protein phosphatase inhibitors are useful when deciphering physiological events regulated by reversible protein phosphorylation ... NSC 95397 is a potent, selective Cdc25 dual specificity phosphatase inhibitor with Ki of 32 nM, 96 nM, 40 nM for Cdc25A, Cdc25B ... also inhibits EGF-induced Erk1/2 activation in HEK293 cells and significantly reduces MDA-MB-468 cell viability/proliferation. ... Sodium Monofluorophosphate (NSC248) is a competitive inhibitor of pyruvate kinase and alkaline phosphatase with Ki of 3.4 mM ...
OPUS Würzburg | Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins
... dual-specificity phosphatase 4 (Dusp4), and tumor-associated antigen L6 (Taal6). Interestingly, most genes were blocked in ... Proliferation and migration of siRNA-treated melanoma cell lines were then investigated. Results: Genes with the strongest ... Knockdown of FOSL1 in human melanoma cell lines reduced their proliferation and migration. Conclusion: Altogether, the data ... The expression of these genes was also monitored in human melanoma cell lines, and the target gene FOSL1 was knocked down by ...
OPUS Würzburg | Search
... dual-specificity phosphatase 4 (Dusp4), and tumor-associated antigen L6 (Taal6). Interestingly, most genes were blocked in ... MMP13 mediates cell cycle progression in melanocytes and melanoma cells: in vitro studies of migration and proliferation (2010 ... Conclusion: Altogether, the data show that the receptor tyrosine kinase Xmrk is a useful tool in the identification of target ... Proliferation and migration of siRNA-treated melanoma cell lines were then investigated. Results: Genes with the strongest ...
Regulation of Mitogen-Activated Protein Kinase Phosphatase-1 in Vascular Smooth Muscle Cells | Hypertension
... is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo. Cell. 1993;75:487-493. ... also referred to as c-Jun N-terminal kinase (JNK), and p38 MAP kinase are suggested to inhibit cellular proliferation and to ... MAP kinase/ERK kinase).3 MEK, the specific activator of ERK, is a dual-specificity protein kinase that phosphorylates both ... The dual specificity mitogen-activated protein kinase phosphatase-1 and -2 are induced by the p42/p44 MAPK cascade. J Biol Chem ...
Abstract B34: Angiotensin-(1-7) attenuates the proliferation of cancer-associated fibroblasts in triple negative breast cancer ...
... dual specificity phosphatase 1) in cancer-associated fibroblasts (n=3, p,0.05). These studies suggest that Ang-(1-7) promotes ... including activation of the MAP kinase pathway to stimulate fibroblast proliferation. TGF-β activates tumor-promoting cancer- ... Abstract B35: BMP regulation of cancer stem cell quiescence is responsible for chemotherapeutic resistance in glioblastoma ... In contrast, incubation of the heptapeptide hormone resulted in a 2.5-fold increase in the MAPK phosphatase DUSP1 ( ...
Amphibian Zic Genes | Springer for Research & Development
Caunt CJ, Keyse SM (2013) Dual-specificity MAP kinase phosphatases (MKPs): shaping the outcome of MAP kinase signalling. FEBS J ... The role of zic genes in cell proliferation vs. differentiation remains unclear, and the activities of Zic factors as ... Sakurada T, Mima K, Kurisaki A, Sugino H, Yamauchi T (2005) Neuronal cell type-specific promoter of the alpha CaM kinase II ... Davey CF, Moens CB (2017) Planar cell polarity in moving cells: think globally, act locally. Development 144(2):187-200. https ...
YopH, N-terminal - Wikipedia
... pTyr-specific phosphatases dual specificity phosphatases (dTyr and dSer/dThr) Cdc25 phosphatases (dTyr and/or dThr) LMW (low ... and cell cycle control, and are important in the control of cell growth, proliferation, differentiation and transformation. The ... "The nonreceptor protein tyrosine phosphatase corkscrew functions in multiple receptor tyrosine kinase pathways in Drosophila". ... Paul S, Lombroso PJ (November 2003). "Receptor and nonreceptor protein tyrosine phosphatases in the nervous system". Cell. Mol ...
Tay Bridge Is a Negative Regulator of EGFR Signalling and Interacts with Erk and Mkp3 in the Wing | proLékaře.cz
Both nuclear-cytoplasmic shuttling of the dual specificity phosphatase MKP-3 and its ability to anchor MAP Kinase in the ... where it promotes cell proliferation and survival . In tay or Mkp3 mutant backgrounds, a fraction of these cells initiates ... function mutation in p42 MAP kinase leads to enhanced signalling and reduced sensitivity to dual specificity phosphatase action ... Mkp3 is a dual-specificity phosphatase that is predominantly localised in the cytoplasm, but it shuttles between the nucleus ...
SMART: LMWPc domain annotation
2) dual specificity phosphatases (dTyr and dSer/dThr). *(3) Cdc25 phosphatases (dTyr and/or dThr) ... and cell cycle control, and are important in the control of cell growth, proliferation, differentiation and transformation [( ... These enzymes are key regulatory components in signal transduction pathways (such as the MAP kinase pathway) ... CRYSTAL STRUCTURE OF A HUMAN LOW MOLECULAR WEIGHT PHOSPHOTYROSYL PHOSPHATASE. IMPLICATIONS FOR SUBSTRATE SPECIFICITY. ...
C16orf71 - wikidoc
DUSP3 (dual specificity phosphatase 3) Negative regulation of multiple enzymatic cascades and signaling pathways Positive ... TYK2 (tyrosine kinase 2) Cellular differentiation, migration, and proliferation in immune cells ... cell proliferation, apoptosis, and cell differentiation in those tissue types. 1357 bp of the gene are antisense to spliced ... Additional related processes included the formation and differentiation of B cells, T cells, endothelial cells, endoderm, and ...
SMART: PTPc domain annotation
... thus activating the kinase and allowing cell cycle progression. The catalytic domain of this dual-specificity phosphatase has ... and cell cycle control, and are important in the control of cell growth, proliferation, differentiation and transformation [( ... The tyrosine and dual-specificity phosphatases are involved in signaling, cell growth and differentiation, and the cell cycle. ... The protein-tyrosine phosphatases (PTPases) superfamily consists of tyrosine-specific phosphatases, dual specificity ...
anti-ERK2 antibody (AA 219-358) | Product No. ABIN967747
Activation of ERK is normally transient and cells possess dual specificity phosphatases that are responsible for its down- ... mitogen-activated protein kinases) are activated after cell stimulation by a wide variety of hormones and growth factors. Cell ... Myriad proteins represent the downstream effectors for the active ERK and implicate it in the control of cell proliferation and ... anti-Mitogen-Activated Protein Kinase Kinase 1 Antibodies * anti-Mitogen-Activated Protein Kinase Kinase 1 Interacting Protein ...
Mitogen-activated protein kinase phosphatase 1/dual specificity phosphatase 1 mediates glucocorticoid inhibition of osteoblast...
However, an inhibitor of the MAPK/ERK kinase-ERK pathway inhibited osteoblast proliferation whereas inhibitors of c-jun N- ... We provide causal evidence that this effect of GC is mediated by induction of the dual-specificity MAPK phosphatase, MKP-1/ ... terminal kinase or p38 MAPK had no effect, suggesting that ERK is the MAPK that controls osteoblast proliferation. Regulation ... Neither c-jun N-terminal kinase nor p38 MAPK is activated by the mitogenic cocktail in 20% fetal calf serum, but their ...
Dual-specificity map kinase phosphatases in health and disease. Biochim Biophys Acta Mol Cell Res 1866(1): 124-143, 2019. PMID ... Downregulation of dual-specificity phosphatase 4 enhances cell proliferation and invasiveness in colorectal carcinomas. Cancer ... Dual-specificity protein phosphatase 4 (DUSP4), also known as mitogen-activated protein kinase phosphatase (MKP)-2, negatively ... Targeting dual-specificity phosphatases: Manipulating map kinase signalling and immune responses. Nat Rev Drug Discov 6(5): 391 ...
Dual-specificity phosphatase 1 ubiquitination in extracellular signal-regulated kinase-mediated control of growth in human...
... inhibition of proliferation and induction of apoptosis in human hepatoma cell lines. Taken together, the present data indicate ... Dual-specificity phosphatase 1 ubiquitination in extracellular signal-regulated kinase-mediated control of growth in human ... Here, we evaluated the effects of the functional interactions of ERK proteins with dual-specificity phosphatase 1 (DUSP1), a ... Dual-specificity phosphatase 1 ubiquitination in extracellular signal-regulated kinase-mediated control of growth in human ...
anti-BEDF mAb (PK33-5B8) - Order from Adipochem
Members of the protein tyrosine phosphatase superfamily cooperate with protein kinases to regulate cell proliferation and ... Dual specificity phosphatase 13 (Also known as BEDP; MDSP; TMDP; SKRP4; DUSP13A; DUSP13B) is an enzyme that in humans is ... One family, the dual specificity phosphatases (DSPs) acts on both phosphotyrosine and phosphoserine/threonine residues. This ... Exhibits intrinsic phosphatase activity towards both phospho-seryl/threonyl and -tyrosyl residues of myelin basic protein, with ...
Context-specific flow through the MEK/ERK module produces cell- and ligand-specific patterns of ERK single and double...
The dual specificity mitogen-activated protein kinase phosphatase-1 and −2 are induced by the p42/p44MAPK cascade. J. Biol. ... In HaCaT A5 cells, IL-6 stimulates proliferation and migration (31). Thus, these model systems represent cells from two ... Differential regulation of MAP kinase signalling by dual-specificity protein phosphatases. Oncogene 26, 3203-3213 (2007).. ... In the ERK pathway, the dual-specificity kinase MEK phosphorylates a threonine and a tyrosine residue in ERK, and this dual- ...
Cancers | Free Full-Text | The Endometriotic Tumor Microenvironment in Ovarian Cancer | HTML
The unique tumor microenvironment of endometriosis is composed of epithelial, stromal, and immune cells, which adapt to survive ... and clear-cell adenocarcinoma. An important clinical caveat to the association of endometriosis with ovarian cancer is the ... Hsiao, K.Y.; Chang, N.; Lin, S.C.; Li, Y.H.; Wu, M.H. Inhibition of dual specificity phosphatase-2 by hypoxia promotes ... downregulation leads to increased angiogenesis and proliferation through activation of extracellular signal-regulated kinase ( ...
Effects of Lovastatin on MDA-MB-231 Breast Cancer Cells: An Antibody Microarray Analysis
Among the proteins related to cell proliferation, the cyclin-dependent kinase inhibitor p57Kip2, the dual-specificity ... phosphatase CDC14A and the co-chaperone protein CDC37 were up-regulated; whereas cyclin-dependent kinase CDK4, chromatin DNA- ... Cell lysate preparation. Whole cell lysates were prepared from cultured cells using 1X cell lysis buffer (Cell Signaling ... Cell proliferation and differentiation markers. Inhibition of cell proliferation was another effect exerted by lovastatin in ...
The role of the inositol polyphosphate 5-phosphatases in cellular function and human disease | Biochemical Journal
... downstream of tyrosine kinase; DYRK1A, dual-specificity tyrosine-phosphorylated and -regulated kinase 1A; EH, Eps15 homology; ... Gene-targeted deletion of 5-ptases in mice has revealed that these enzymes regulate haemopoietic cell proliferation, synaptic ... B-cell receptor; Btk, Brutons tyrosine kinase; Cdk5, cyclin-dependent kinase 5; CHO, Chinese-hamster ovary; CHO-IR, CHO cells ... Phosphoinositides are membrane-bound signalling molecules that regulate cell proliferation and survival, cytoskeletal ...
MAP kinase phosphatases
They are responsible for the induction of a number of cellular responses, such as changes in gene expression, proliferation, ... Mitogen-activated protein MAP kinases are key signal-transducing enzymes that are activated by a wide range of extracellular ... An emerging family of structurally distinct dual-specificity serine, threonine and tyrosine phosphatases that act on MAP ... cell cycle arrest and apoptosis. Although regulation of MAP kinases by a phosphorylation cascade has long been recognized as ...
Gene Expression Changes Induced by Trypanosoma cruzi Shed Microvesicles in Mammalian Host Cells: Relevance of tRNA-Derived...
C. J. Caunt and S. M. Keyse, "Dual-specificity MAP kinase phosphatases (MKPs): shaping the outcome of MAP kinase signalling," ... cell growth, proliferation, cytoskeleton regulation, and survival pathways [32-34]. ... "Diverse physiological functions for dual-specificity MAP kinase phosphatases," Journal of Cell Science, vol. 119, no. 22, pp. ... Finally, DUSP6 is a dual-specificity phosphatase, which belongs to the MAPK phosphatase family, with specificity for ...
Pro‑apoptotic effects of pycnogenol on HT1080 human fibrosarcoma cells
Dual specificity phosphatase 1. Inhibits proliferation and induces apoptosis in human hepatocellular and pancreatic carcinoma. ... Promotes human lung cancer cell invasion and metastasis in vitro and in vivo. Promotes proliferation and cell survival of ... Mitogen-activated protein kinase 8. Contributes to apoptosis induced by cytostatics in different sarcoma cell lines. 0.5. 60. ... Associated with increased cell survival of synovial sarcoma cells. −1.1. 39. LAMC1. Laminin γ1. Contributes to cancer cell ...
Glucocorticoid-dependent expression of IAP participates in the protection against TNF-mediated cytotoxicity in MCF7 cells | BMC...
... induced cell death has been well characterized in MCF7 luminal A breast cancer cells. The GR activates a variety of protective ... MCF7 cells were used for all experiments. GR was activated with cortisol (CORT) or dexamethasone (DEX) and inhibited with ... the relative contribution of the GR-dependent expression of IAPs in the protection of cell death has not, to our knowledge, ... mifepristone (RU486). Cell viability was determined in real-time with the xCELLigence™ RTCA System and at specific endpoints ...
PathwayMAPKSerineInhibitorsSubstrate specificityRegulationGeneResiduesDephosphorylatesPhosphoprotein PhosphatasesRegulatesDUSPsCytoplasmicMKPsCatalytic domainMolecular2018ERK2VitroMRNAPhosphorylatesSignal transducer and activator of transcriptionStimulationDownstreamNegativelyInactivationMAPK1Phosphatidylinositol 3-kinaProtein tyrosine phosphatase suReceptorsEpithelial cellMetabolism
- A pathway/functional analysis of celecoxib-affected transcripts, using Gene Ontology and Biocarta Pathways and exploring biological association networks, revealed that celecoxib modulates expression of numerous genes involved in a variety of cellular processes, including metabolism, cell proliferation, apoptotic signaling, cell cycle check points, lymphocyte activation, and signaling pathways. (aacrjournals.org)
- One potential mechanism of how hypoxia/HIF-1 may lead to activation of ERK pathway is via regulation of dual-specificity phosphatase 2 (DUSP2). (aacrjournals.org)
- Cyclosporine is a calcineurin phosphatase pathway inhibitor, used as an immunosuppressant drug to prevent rejection in organ transplantation. (selleckchem.com)
- These data suggest the induction of MKP-1, not only after stimulation of the cell growth-promoting ERK pathway but also in response to activation of stress-responsive MAP kinase signaling cascades. (ahajournals.org)
- These studies suggest that Ang-(1-7) promotes the dephosphorylation of MAPK by up-regulating DUSP1 to reduce this proliferative signaling pathway in cancer-associated fibroblasts and prevent tumor growth. (aacrjournals.org)
- TGF-β is a potent stimulator of fibroblast activation and plays an important role in promoting fibrosis, including activation of the MAP kinase pathway to stimulate fibroblast proliferation. (aacrjournals.org)
- The Epidermal Growth Factor Receptor (EGFR) signalling pathway is a conserved module that plays multiple roles during development and tissue homeostasis in eukaryotic organisms  - . (prolekare.cz)
- However, an inhibitor of the MAPK/ERK kinase-ERK pathway inhibited osteoblast proliferation whereas inhibitors of c-jun N-terminal kinase or p38 MAPK had no effect, suggesting that ERK is the MAPK that controls osteoblast proliferation. (ox.ac.uk)
- In the ERK pathway, the dual-specificity kinase MEK phosphorylates a threonine and a tyrosine residue in ERK, and this dual-phosphorylated form is the fully active kinase. (sciencemag.org)
- The Notch signaling pathway is a reiteratively used cell to cell communication pathway that triggers pleiotropic effects. (biomedcentral.com)
- The correct regulation of the pathway permits the efficient regulation of genes involved in cell fate decision throughout development. (biomedcentral.com)
- This activity relies notably on the CSL proteins, (an acronym for C BF-1/RBPJ-κ in Homo sapiens / Mus musculus respectively, S uppressor of Hairless in Drosophila melanogaster , L ag-1 in Caenorhabditis elegans ) which is the unique transcription factor and DNA binding protein involved in this pathway. (biomedcentral.com)
- The aim of this review is to describe the different co-repressor proteins that interact directly with CSL proteins to form repression complexes thereby regulating the Notch signaling pathway in animal cells to give insights into the paralogous evolution of these co-repressors in higher eumetazoans and their subsequent effects at developmental processes. (biomedcentral.com)
- General view of the NSP: once a ligand of the DSL family in the signal sending cell interacts with the Notch receptor of the signal receiving cell, NICD is released by proteolysis and translocated to the nucleus activating the pathway for a positive gene regulation together with CSL proteins, Mastermind (Mam) protein and histone acetyltransferases (HATs). (biomedcentral.com)
- The p44/42 MAPK (Erk1/2) signaling pathway can be activated in response to a diverse range of extracellular stimuli including mitogens, growth factors, and cytokines (1-3), and research investigators consider it an important target in the diagnosis and treatment of cancer (4). (cellsignal.com)
- Since their discovery in the 1980s, MAPKs have been extensively studied (for a historic description, see Avruch [ 1 ]) and several reports show that this signaling pathway is highly conserved amongst eukaryotes. (mdpi.com)
- MAPK pathway is composed of multiple molecules that also transduce signals in other cascades, creating a crosstalk and a wide intracellular network that involves other pathways such as PI3-kinase (PI3K)-Akt, Src, Smad and Wnt-β catenin. (mdpi.com)
- The Ras/mitogen-activated protein kinase (MAPK) signaling pathway has long been identified as a convergence point for numerous (normal and pathologic) signaling inputs, rendering it an appealing target for therapeutic intervention ( 4 ). (aacrjournals.org)
- No such genes were identified in RTK tumor cells, suggesting that ERK pathway signaling output is selectively activated in BRAF mutant tumors. (pnas.org)
- Hyperactivation of the pathway results in dysregulated cell proliferation and malignant transformation in model systems and occurs commonly in human tumors. (pnas.org)
- It is possible that ERK output is elevated in both tumors with RTK activation and tumors with BRAF mutation, but that the pathway is necessary for proliferation only in the latter. (pnas.org)
- The extracellular regulated kinase (ERK) pathway is activated by a large variety of mitogens and growth factors, whereas the c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) and p38 pathways are stimulated mainly by environmental stress and inflammatory cytokines. (bio-rad.com)
- The ERK pathway, which includes the regulation and signaling cascade of Mitogen-activated protein kinases 3 and 1 ( ERK1/2 ), is involved in cell growth, proliferation and survival [ 1 ]. (bio-rad.com)
- In general, dephosphorylation of MAPKs decreases their kinase activity that is essential for cell to remain responsive to stimuli and to prevent deleterious effects of prolonged pathway stimulation [ 1 ], [ 2 ]. (bio-rad.com)
- ERK pathway phosphatases are classified according to their substrate specificities into dual-specificity MAPK phosphatases, protein serine/threonine phosphatases, and protein tyrosine phosphatases. (bio-rad.com)
- NSC 95397 inhibits mitogen-activated protein kinase phosphatase-1 (MKP-1) and suppresses proliferation and induces apoptosis in colon cancer cells through MKP-1 and ERK1/2 pathway . (medchemexpress.cn)
- This results in defective inhibitory signaling and as a consequence, Lyn-deficient B cells are hyperresponsive to BCR stimulation and show enhanced proliferation, calcium flux, and activation of the mitogen-activated protein kinase pathway ( 15 - 19 , 23 ). (rupress.org)
- The phosphatidylinositol 3-kinase (PI3K) pathway is a major determinant of cell cycling and proliferation. (aspetjournals.org)
- Rcan1-4 is definitely upregulated by raises in [Ca2+]i in several cell types including mind cells via a CN/NFAT-dependent pathway [12- (bioentryplus.com)
- HIF-1 can bypass the lapatinib-treated inhibition of the ERK pathway via inhibition of the dual-specificity phosphatase 2 (DUSP2). (nih.gov)
- Zhao H, Watkins JL, Piwnica-Worms H: Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints. (hmdb.ca)
- The classic MAPK1/3 activation pathway involves the sequential activation of the serine/threonine kinase Raf, a dual-specificity MAPK kinase (MAPKK or MEK) and then the MAPK ( Sebolt-Leopold and Herrera, 2004 ). (biologists.org)
- Activation of the Raf-MAPKK-MAPK kinase pathway transmits signals to both cytoplasmic signaling complexes and nuclear transcription factors, including protein kinases and phosphatases, signaling effectors, transcriptional regulators and cytoskeletal proteins ( Yoon and Seger, 2006 ). (biologists.org)
- 2020). Targeting Rad51 as a strategy for the treatment of melanoma cells resistant to MAPK pathway inhibition . (genecopoeia.com)
- 2019). Down-regulated expression of LINC00518 prevents epithelial cell growth and metastasis in breast cancer through the inhibition of CDX2 methylation and activation of the Wnt signaling pathway . (genecopoeia.com)
- There were differentially expressed genes between PE and P-M and between RPE and P-RE, of which gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis were mainly enriched in cell proliferation, the p53 signaling pathway, etc. (bvsalud.org)
- The mitogen-activated protein kinase (MAPK) cascade is a predominant pathway for cell growth and proliferation. (aacrjournals.org)
- Here, we discuss how therapy using PI3K pathway inhibitors could benefit from information on specific phosphatases, which naturally antagonize the kinase targets. (aacrjournals.org)
- Upon completion of this activity, the participant should have a better understanding of the lipid and protein phosphatases that regulate the PI3K pathway and their potential application as biomarkers to improve patient stratification, prediction of therapeutic responses, and disease outcomes in patients with cancer. (aacrjournals.org)
- Today we know that this pathway constitutes the major oncogenic signaling axis next to the RAS/mitogen-activated protein kinase pathway. (aacrjournals.org)
- Core phosphatases of the PI3K pathway. (aacrjournals.org)
- Although p90 ribosomal S6 kinase (RSK) is known as an important downstream effector of the ribosomal protein S6 kinase/extracellular signal-regulated kinase (Ras/ERK) pathway, its endogenous role, and precise molecular function remain unclear. (sdbonline.org)
- Many negative regulators of the Ras/ERK pathway including various dual-specificity phosphatases are transcriptionally induced by activation of the Ras/ERK pathway to form a negative feedback loop. (sdbonline.org)
- Earlier, stromal interaction molecule 1 (STIM1) was identified as an important signaling molecule in the CRAC channel pathway using limited RNAi screens ( 7 , 8 ). (jimmunol.org)
- Protein tyrosine kinase Syk is associated with and activated by the IL-2 receptor: possible link with the c-myc induction pathway. (wikipathways.org)
- Gab1 transduces PI3K-mediated erythropoietin signals to the Erk pathway and regulates erythropoietin-dependent proliferation and survival of erythroid cells. (wikipathways.org)
- This pathway participates in the control of numerous processes including apoptosis, cell proliferation, the immune response, nervous system function, and RNA synthesis and processing. (selleckchem.com)
- The linear MAP kinase pathway branches extensively at the ERK1/2 node. (selleckchem.com)
- Although numerous cancers are driven by MAP kinase pathway activation, thus far the only orally effective approved drugs that target this signaling module are used for the treatment of BRAF-mutant melanomas. (selleckchem.com)
- Owing to the large variety of malignancies that are driven by dysregulation of the MAP kinase pathway, additional tumor types should be amenable to MAP kinase pathway inhibitor therapy. (selleckchem.com)
- Additional work will be required to determine whether ERK inhibitors will be successful in the clinic and are able to forestall the development of drug resistance of the MAP kinase pathway. (selleckchem.com)
- This study aimed to discuss the regulatory mechanism of Extracellular Signal-Regulated Kinase (ERK) signal pathway for DNA methylation in lung carcinoma cells. (alliedacademies.org)
- ERK signal pathway blocked both proliferation rate of lung carcinoma cells and DNA methylation level because of the down-regulation of Dnmts mRNA and their protein expression levels and the up-regulation of cancer suppressor genes p16 and RASSF1A mRNA and their protein expression levels. (alliedacademies.org)
- DNA methylation and extracellular regulated protein kinase-motogen-activated protein kinases signal transduction pathway mediate or regulate relevant genetic expressions in the genesis and development of lung carcinoma [ 4 ]. (alliedacademies.org)
- However, further study is needed on the regulatory mechanism of ERK signal pathway for the DNA methylation of lung carcinoma cells [ 5 ]. (alliedacademies.org)
- In the current study, this was carried out by applying ERK signal pathway agonist and blocker in cells in vitro . (alliedacademies.org)
- Each MAPK pathway contains a three-tiered kinase cascade comprising a MAP kinase kinase kinase (MAPKKK, MAP3K, MEKK or MKKK), a MAP kinase kinase (MAPKK, MAP2K, MEK or MKK) and the MAPK. (biologists.org)
- Pathway specificity is regulated at several levels, including kinase-kinase and kinase-substrate interactions, colocalization of kinases by scaffold proteins, and inhibition of cross-talk/output by the MAPKs themselves. (biologists.org)
- Continuous basal repression of MAPKs by phosphatases occurs and may poise a pathway for activation above a particular threshold. (biologists.org)
- MAPK phosphatases (MKPs) are the largest class of phosphatases involved in down-regulating Mitogen-activated protein kinases (MAPK) signaling. (wikipedia.org)
- MAPK phosphatases are therefore important regulator components of these pathways. (wikipedia.org)
- MAPK phosphatases are only found in eukaryotes and negatively regulate MAP kinases to act as negative feedback. (wikipedia.org)
- MKPs are also known as dual-specificity phosphatases (DUSPs) because they deactivate MAPK by dephosphorylating the Threonine and the Tyrosine residues residing in MAPKs activation site. (wikipedia.org)
- The newest MKP, MKP-8, belongs to group I because it is located in the nuclear region of the cell A recent study shows that histone deacetylase isoforms (HDAC1, -2, and -3) deacetylate MKP-1 and that this post-translational modification increases MAPK signaling and innate immune signaling. (wikipedia.org)
- In MKP-1, MAPK binds to the active site that is between the CH2A and CHB domains located in the N-terminal. (wikipedia.org)
- MAPK Phosphatases at the US National Library of Medicine Medical Subject Headings (MeSH) Dickinson, Robin J. (wikipedia.org)
- However, neither MAPK nor MMP activity were required for migration, as the cells migrated in an entirely amoeboid mode. (uni-wuerzburg.de)
- We provide causal evidence that this effect of GC is mediated by induction of the dual-specificity MAPK phosphatase, MKP-1/DUSP1. (ox.ac.uk)
- Neither c-jun N-terminal kinase nor p38 MAPK is activated by the mitogenic cocktail in 20% fetal calf serum, but their activation by a DNA-damaging agent (UV irradiation) was inhibited by either GC treatment or overexpression of MKP-1, indicating regulation of all three MAPKs by MKP-1 in osteoblasts. (ox.ac.uk)
- Background/Aim: Dual-specificity protein phosphatase 4 (DUSP4) negatively regulates MAPK signaling and is involved in various cellular processes. (iiarjournals.org)
- Dual-specificity protein phosphatase 4 (DUSP4), also known as mitogen-activated protein kinase phosphatase (MKP)-2, negatively regulates mitogen-activated protein kinase (MAPK) signaling and is involved in various cellular processes such as cell proliferation and immune response ( 4 ). (iiarjournals.org)
- Upon stimulation, a sequential three-part protein kinase cascade is initiated, consisting of a MAP kinase kinase kinase (MAPKKK or MAP3K), a MAP kinase kinase (MAPKK or MAP2K), and a MAP kinase (MAPK). (cellsignal.com)
- p44/42 are negatively regulated by a family of dual-specificity (Thr/Tyr) MAPK phosphatases, known as DUSPs or MKPs (10), along with MEK inhibitors, such as U0126 and PD98059. (cellsignal.com)
- However, in addition to these, the variety of stimuli and the specific expression of proteins in the different cell types increase the complexity of MAPK system [ 4 ]. (mdpi.com)
- Growing evidence suggests that the Ras/mitogen-activated protein kinase (MAPK) signaling cascade represents a pivotal molecular circuitry participating directly or indirectly in prostate cancer evolution. (aacrjournals.org)
- PP2A catalytic dephosphorylates and blocks activation of both ERK1/2 and its upstream kinase, Mitogen-activated protein kinase kinase 1 ( MEK1(MAP2K1) ), determining the kinetics of MAPK cascades [ 4 ], [ 5 ]. (bio-rad.com)
- Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204) (D13.14.4E) XP ® Rabbit mAb (Alexa Fluor ® 488 Conjugate) detects endogenous levels of p44 and p42 MAP Kinase (Erk1 and Erk2) when either dually phosphorylated at Thr202 and Tyr204 of Erk1 (Thr185 and Tyr187 of Erk2), or singly phosphorylated at Thr202. (cellsignal.com)
- Spatio-temporal control of extracellular signal-regulated kinase (ERK) activity, a critical determinant of the cell's response to growth factors, requires timely dephosphorylation of its regulatory tyrosine and/or threonine residue by MAPK phosphatases. (biomedcentral.com)
- The finding that robust changes in tyrosine-specific MAPK phosphatase expression levels have minor effects on temporal ERK1/2 activity control in PC12 cells suggests that dual-specificity MAPK phosphatases may act as major regulators of growth factor-induced ERK1/2 signaling in these cells. (biomedcentral.com)
- It has become clear that it is not just the amplitude but also the spatio-temporal distribution of the MAPK activity within the cell that determines the final outcome of this signaling relay. (biomedcentral.com)
- Concomitantly, ERK inactivation involves dephosphorylation of these residues by MAPK phosphatases. (biomedcentral.com)
- Although the EGF and NGF specific pathways that lead to ERK activation have been mapped in detail in PC12 cells [ 3 ], the contribution of MAPK phosphatases in this model system has received little attention. (biomedcentral.com)
- The latter two types have gained considerable interest because they contain a so-called kinase interaction motif (KIM) that is also present in the upstream MAPK kinases MEK1/2. (biomedcentral.com)
- We find that ERK activity is essential for serum-induced osteoblast proliferation in vitro because inhibition of MAPK/ERK kinase activity by U0126 completely abolished both serum-induced activation of ERK and proliferation of mouse (MBA-15.4) and human (MG-63) osteoblast cell lines. (ox.ac.uk)
- Coupled with the rapidity of Dex action, this indicates immediate-early gene phosphatase involvement, and we therefore used quantitative, real-time PCR to examine expression profiles of the dual-specificity MAPK phosphatases, MKP-1 and MKP-3. (ox.ac.uk)
- ERK1/2 are negatively regulated by a family of dual-specificity (Thr/Tyr) MAPK phosphatases. (ecmbiosciences.com)
- BOP1 knockdown promoted down-regulation of the MAPK phosphatases DUSP4 and DUSP6 via a transcription-based mechanism, leading to increased MAPK signaling and BRAFi resistance. (pnas.org)
- Monitoring protein-protein interactions (PPIs) of MAPKs with MAPK phosphatases in vivo provides valuable information about specificity and intracellular localization of the protein complex. (springer.com)
- Here, we report studying PPIs between Arabidopsis MAPKs and PP2C-type MAPK phosphatases using bimolecular fluorescent complementation (BiFC) in suspension cell protoplasts. (springer.com)
- We report here that p53 regulates DUSP1 , a dual-specific threonine and tyrosine phosphatase with stringent substrate specificity for mitogen-activated protein kinase (MAPK). (aacrjournals.org)
- In contrast, MAPKs are inactivated upon dephosphorylation of tyrosine and threonine residues by MAPK phosphatases, including DUSP1, MKP2, and PAC1 ( 18 , 19 ). (aacrjournals.org)
- Activation of the receptor-coupled G protein initiates a four-tiered cascade of protein kinases, ultimately resulting in stimulation of a messenger-activated protein kinase or MAPK (Fus3) that translocates into the nucleus. (berkeley.edu)
- Subjecting cells to hyperosmotic conditions activates yet another MAPK (Hog1). (berkeley.edu)
- Thus, MAPK cascades are universally employed in eukaryotic cells for mounting an appropriate response to an extracellular stimulus and, like yeast, every eukaryotic cell contains multiple MAPK pathways. (berkeley.edu)
- We showed that one device used by the cell for discrimination between parallel MAPK pathways is a specific docking interaction between a MAPK and the N-terminus of its cognate upstream protein kinase (MEK). (berkeley.edu)
- We also showed that the scaffold protein Ste5 helps ensure signaling fidelity in pheromone response by binding the appropriate MAPK (Fus3), MEK (Ste7), and upstream activating kinase or MEKK (Ste11) and by shuttling from the nucleus to the plasma membrane, thereby delivering the MAPK module to its most proximal activator- a fourth plasma membrane-associated protein kinase (Ste20). (berkeley.edu)
- Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. (wikipathways.org)
- They exhibit great specificity for their cognate MAPK but are regulated by many MAPKKKs. (biologists.org)
- MAPKs are attenuated by dual specificity MAPK phosphatases (MKPs), tyrosine phosphatases and serine/threonine phosphatases ( Keyse, 2000 ). (biologists.org)
- MAPK phosphatases may attenuate MAPKs in a site-specific manner. (biologists.org)
- Ser/Thr and Tyr dual specificity phosphatases are a group of enzymes with both Ser/Thr ( EC:220.127.116.11 ) and tyrosine specific protein phosphatase ( EC:18.104.22.168 ) activity able to remove both the serine/threonine or tyrosine-bound phosphate group from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (ebi.ac.uk)
- A shallow active site pocket in VHR allows for the hydrolysis of phosphorylated serine, threonine, or tyrosine protein residues, whereas the deeper active site of protein tyrosine phosphatases (PTPs) restricts substrate specificity to only phosphotyrosine. (ebi.ac.uk)
- In general, upon activation by Mek, the Erk serine/threonine kinase is transported into the nucleus, where it can phosphorylate specific transcription factors, regulating their activity and consequently gene expression. (prolekare.cz)
- An emerging family of structurally distinct dual-specificity serine, threonine and tyrosine phosphatases that act on MAP kinases consists of ten members in mammals, and members have been found in animals, plants and yeast. (nih.gov)
- Basically, CDKs are serine/threonine kinases consisting of a catalytic subunit (CDK) and a regulatory subunit (Cyclin). (omicsonline.org)
- A cholesterol-regulated Protein phosphatase 2A ( PP2A catalytic )/ Protein tyrosine phosphatase, non-receptor type 7 ( HePTP ) complex dephosphorylates both the phosphotyrosine and the phosphothreonine residues in the activation loop of ERK1/2 due to the combined activities of the serine/threonine phosphatase PP2A catalytic and the tyrosine phosphatase HePTP [ 3 ]. (bio-rad.com)
- The dephosphorylation of ERK1/2 regulatory tyrosine and threonine residues can be achieved by three different phosphatase types: protein serine/threonine phosphatases, dual specificity (serine/threonine/tyrosine) phosphatases (MKPs/DUSPs) and classical phosphotyrosine-specific protein tyrosine phosphatases (PTPs) [ 5 ]. (biomedcentral.com)
- The importance of PH domain-mediated interactions with the plasma membrane is well illustrated by the mechanisms of activation of the ubiquitous serine/threonine kinase Akt (also known as protein kinase B) and the B-cell and mast cell protein tyrosine kinase (PTK) Btk. (asm.org)
- those that phosphorylate tyrosine residues (protein tyrosine kinases, PTK) and those that phosphorylate serine or threonine residues (serine/threonine kinases, STK). (patentgenius.com)
- The dual-specificity phosphatase (DUSP) belongs to family of protein group which is able to dephosphorylate the residues of threonine/serine and tyrosine. (scitechnol.com)
- The dephosphorylation and inactivation of ERK1/2 is catalyzed by dual specificity phosphatases, protein-tyrosine specific phosphatases, and protein-serine/threonine phosphatases. (selleckchem.com)
- In V600E BRAF cells, this output is comprised of 52 genes, including transcription factors that regulate transformation and members of the dual specificity phosphatase and Sprouty gene families, feedback inhibitors of ERK signaling. (pnas.org)
- The proliferation of tumors with BRAF mutation is sensitive to inhibition of ERK signaling with selective inhibitors of MEK ( 12 ). (pnas.org)
- Identification of a potent and selective pharmacophore for Cdc25 dual specificity phosphatase inhibitors. (medchemexpress.cn)
- The catalytic subunits of protein kinases are highly conserved, and several structures have been solved [ PMID: 15078142 ], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [ PMID: 15320712 ]. (ebi.ac.uk)
- Tubulin and topoisomerase II were assumed to be promising targets for cell proliferation inhibitors in KC. (mpg.de)
- Cell extract selleck ALK Inhibitors was then boiled for 10 min and kept at 80 C. Western blots were per formed in duplicate with ten 30 ug total proteins making use of regular SDS Webpage procedures. (narturalproducts.com)
- Thus, BRAF kinase inhibitors (BRAFi), such as vemurafenib and dabrafenib, have been developed and used for the treatment of BRAF-mutant metastatic melanoma in clinic. (pnas.org)
- Acquired resistance to BRAF kinase inhibitors (BRAFi) is the primary cause for their limited clinical benefit. (pnas.org)
- These findings have led to the development and approval of several BRAF and MEK kinase inhibitors by the Food and Drug Administration for treating unresectable metastatic melanoma ( 7 , 8 ). (pnas.org)
- This cell routine arrest happens via the derepression of cyclin-dependent kinase inhibitors, p15 and p27 . (studioinathens.com)
- Auvinen M, Paasinen-Sohns A, Hirai H, Andersson LC, Hölttä E. Ornithine decarboxylase- and ras-induced cell transformations: reversal by protein tyrosine kinase inhibitors and role of pp130CAS. (pubmedcentralcanada.ca)
- Substrate specificities of catalytic fragments of protein tyrosine phosphatases (HPTP beta, LAR, and CD45) toward phosphotyrosylpeptide substrates and thiophosphotyrosylated peptides as inhibitors. (pubmedcentralcanada.ca)
- Specificity and mechanism of action of some commonly used protein kinase inhibitors. (semanticscholar.org)
- In addition, inhibition of SIP kinase activation by kinase inhibitors correlated with the suppression of cell wall elicitor-induced medium alkalization and PAL gene activation, suggesting a regulatory function for the SIP kinase in these defense responses. (plantcell.org)
- The MAP kinase cascade is perhaps the most important oncogenic driver of human cancers and the blockade of this signalling module by targeted inhibitors is an important anti-tumor strategy. (selleckchem.com)
- A "recognition region" connecting helix alpha1 to strand beta1, may determine differences in substrate specificity between VHR, the PTPs, and other DSPs. (ebi.ac.uk)
- Three subgroups have been identified that differ in exon structure, sequence and substrate specificity. (nih.gov)
- Although some histone demethylases possess described substrate specificity, others talk about a number of substrates, and for that reason screen redundancy in regulating chromatin and gene appearance. (studioinathens.com)
- We have investigated the substrate specificity of PTP-PEST by a novel substrate-trapping approach in combination with in vitro dephosphorylation experiments. (pubmedcentralcanada.ca)
- These results provide the first demonstration of a PTP having an inherently restricted substrate specificity in vitro and in vivo. (pubmedcentralcanada.ca)
- Protein kinases and phosphatases that catalyze this process are categorized into two major classes based on their substrate specificity: the Ser/Thr kinases (phosphatases) and the Tyr kinases (phosphatases). (plantcell.org)
- The phosphatase MKP1 is a transcriptional target of p53 involved in cell cycle regulation. (thefreedictionary.com)
- This can involve gene regulation, cell proliferation, programmed cell death and stress responses. (wikipedia.org)
- Protein tyrosine phosphatases: mechanisms of catalysis and regulation. (ebi.ac.uk)
- ARHGAP1, ZNFX1, and MBTPS1 are associated with regulation in signaling and metabolism while PLVAP is associated with the formation of small lipid rafts in the plasma membrane of vertebrate endothelial and adipose cells. (wikidoc.org)
- Regulation of ERK by MKP-1 provides a novel mechanism for control of osteoblast proliferation by GCs. (ox.ac.uk)
- CDK/cyclin complexes regulate each phase of the cell cycle and the breakdown of this regulation in any phase results in uncontrolled growth and thus tumor formation. (omicsonline.org)
- The dual nature of Lyn's role in the regulation of B cell signaling makes it a potentially critical target in analyzing the development of B cell dysfunction. (rupress.org)
- Glucocorticoids induce rapid up-regulation of mitogen-activated protein kinase phosphatase-1 and dephosphorylation of extracellular signal-regulated kinase and impair proliferation in human and mouse osteoblast cell lines. (ox.ac.uk)
- Therefore, MKP-1 up-regulation provides a novel and rapid mechanism, whereby GCs inhibit osteoblast proliferation. (ox.ac.uk)
- Reintroduction of a full-length MPL1 into mpl1 − cells restored aggregation, ERK2 regulation, random and directional motility, and cAMP production similar to wild-type cells. (asm.org)
- Factors involved in the regulation of mesangial cell proliferation in vitro and in vivo. (patentgenius.com)
- 1992). Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms. (patentgenius.com)
- Hypoxia/HIF1α induces lapatinib resistance in ERBB2-positive breast cancer cells via regulation of DUSP2. (nih.gov)
- One possible mechanism of HIF1-mediated ERK activation under hypoxia is regulation of the dual specificity protein phosphatase 2 (DUSP2). (nih.gov)
- Several studies have got referred to that JmJC demethylase activity, using the buy 857531-00-1 appearance or repression of genes, is certainly mixed up in regulation from the cell routine. (studioinathens.com)
- buy 857531-00-1 Another example, histone demethylation in cell routine regulation buy 857531-00-1 entails KDM3A (Fig.?6) which has an important part in human being carcinogenesis. (studioinathens.com)
- This research focuses on the regulation by FSH of extracellular signal-regulated kinase (ERK) and identifies Y-box binding protein-1 (YB-1) as a downstream component of ERK signaling. (wsu.edu)
- Temporal regulation of frankincense oil-activated gene expression in bladder cancer cells was identified by microarray and bioinformatics analysis. (biomedcentral.com)
- New insights into the regulation of T cells by gamma(c) family cytokines. (wikipathways.org)
- Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. (proteopedia.org)
- A gene on chromosome 5q34 that encodes dual-specificity phosphatase 1, a protein which dephosphorylates MAP kinase MAPK1/ERK2. (thefreedictionary.com)
- However, sarcomeric and metabolic gene expression was unaffected or upregulated in ERRα−/− cells. (physiology.org)
- The expression of these genes was also monitored in human melanoma cell lines, and the target gene FOSL1 was knocked down by siRNA. (uni-wuerzburg.de)
- The vaccina H-1 gene product (VH-1) was the first phosphatase shown to effectively hydrolyze both phosphotyrosine and phosphoserine/phosphothreonine. (ahajournals.org)
-  The gene is expressed in epithelial tissue of the respiratory system , adipose tissue , and the testes . (wikidoc.org)
- DUSP13B) is an enzyme that in humans is encoded by the DUSP13 gene . (adipogen.com)
- Gene-targeted deletion of 5-ptases in mice has revealed that these enzymes regulate haemopoietic cell proliferation, synaptic vesicle recycling, insulin signalling, endocytosis, vesicular trafficking and actin polymerization. (biochemj.org)
- Here we analyzed the changes in gene expression of host HeLa cells induced by extracellular vesicles from T. cruzi . (hindawi.com)
- In human tumors, ERK activation occurs as a result of receptor tyrosine kinase (RTK) activation or mutations in members of the RAS and RAF gene families ( 1 , 2 ). (pnas.org)
- Our aim was to evaluate the interaction between breast cancer cells and nodal fibroblasts, by means of their gene expression profile. (springer.com)
- Fibroblast primary cultures were established from negative and positive lymph nodes from breast cancer patients and a similar gene expression pattern was identified, following cell culture. (springer.com)
- MDA-MB231 gene expression profile, as evaluated by cDNA microarray, was influenced by the fibroblasts presence, and HNMT , COMT , FN3K , and SOD2 were confirmed downregulated in MDA-MB231 co-cultured cells with fibroblasts from both negative and positive nodes, in a new series of RT-PCR assays. (springer.com)
- However, little is known about the gene regulatory networks influenced by Runx2 in PCa cells. (biomedcentral.com)
- Consistent with the gene expression data, induction of Runx2 in C4-2B cells enhanced their invasiveness. (biomedcentral.com)
- The JmJC area formulated with histone demethylase 1 (KDM2A) gene encodes an associate from the?F-box protein?family members (Fig.?6) and demethylase with activity towards lysine 36 of histone 3 (H3K36) . (studioinathens.com)
- KDM2A gene is certainly induced under hypoxia circumstances [132, however the system and useful significance toward the hypoxia response happens to buy 857531-00-1 be as yet not known. (studioinathens.com)
- Demethylation of H3K36(2me) on the dual specificity phosphatase 3 (DUSP3) promoter by KDM2A inhibits DUSP3 gene transcription . (studioinathens.com)
- For example, p21 , a gene critical for progression of cells from the G 1 -S phase of the cell cycle, was identified early on as a target for p53 ( 4 ), and the precise promoter sequence bound by p53 was also defined ( 4 ). (aacrjournals.org)
- The two teams immediately saw that the gene encodes a phosphatase, which launched a flurry of investigations for its substrate. (aacrjournals.org)
- Transmembrane and intracellular signal transduction mechanisms are the focus of our group, especially understanding how extracellular stimuli control cell growth and division, cell morphology, and gene expression at the biochemical level. (berkeley.edu)
- Here, we describe the functional analysis of an Arabidopsis gene ( AtPTEN1 ) that encodes a Tyr phosphatase closely related to PTEN, a tumor suppressor in animals. (plantcell.org)
- Suppression of AtPTEN1 gene expression by RNA interference caused pollen cell death after mitosis. (plantcell.org)
- Consistent with these physiological phenotypes, RSK negatively regulates ERK-mediated developmental processes and gene expressions by blocking the nuclear localization of ERK in a kinase activity-independent manner. (sdbonline.org)
- The maximum activation of this kinase paralleled or preceded medium alkalization and activation of the defense gene phenylalanine ammonia-lyase ( PAL ). (plantcell.org)
- RT-PCR and methylation-specific PCR are used to detect mRNA expression and methylation state of DUSP-6 gene in nasopharyngeal carcinoma tissues and CNE2 cell line. (scitechnol.com)
- The changes of mRNA expression and methylation state of DUSP-6 gene, proliferation and invasion of cells were detected after 5-aza- 2'-deoxycytidine (5-aza-cdR) treated CNE2 cell line. (scitechnol.com)
- These results showed that DUSP-6 gene expression is related to its promoter methylation state, cervical lymph node metastasis is related to DUSP-6 gene promoter methylation state in patients with nasopharyngeal carcinoma, 5-aza-cdR can inhibit invasion of CNE2 cells, and make re-expression of DUSP-6 gene by promoter demethylation in CNE2 cells. (scitechnol.com)
- Xu found that Dusp-6 gene is often under-expressed because of its promoter hypermethylation in pancreatic cancer tissues and cell lines [ 3 ]. (scitechnol.com)
- In this study, we have detected the methylation state and expression of DUSP-6 gene in nasopharyngeal carcinoma tissues and CNE2 cell linea nasopharyngeal carcinoma cell line). (scitechnol.com)
- No expression of DUSP- 6 mRNA was found in nasopharyngeal carcinoma tissues of DUSP- 6 gene hypermethylation and CNE2 cell line. (scitechnol.com)
- Demethylation and re-expression of DUSP-6 gene was found, ability of cell invasion were inhibited in CNE2 cells. (scitechnol.com)
- Fluorescent quantitative Polymerase Chain Reaction (qPCR) method was used to test the expression quantities of DNA transmethylase 1 (Dnmt1), DNA transmethylase 3a (Dnmt3a), DNA transmethylase 3b (Dnmt3b), tumor suppressor gene ( p16 ), and Ras association domain family gene ( RASSF1A ) mRNA. (alliedacademies.org)
- One family, the dual specificity phosphatases (DSPs) acts on both phosphotyrosine and phosphoserine/threonine residues. (adipogen.com)
- Exhibits intrinsic phosphatase activity towards both phospho-seryl/threonyl and -tyrosyl residues of myelin basic protein, with similar specific activities in vitro. (adipogen.com)
- CAK phosphorylates the catalytic subunits of CDKs at threonine (Thr 160/161) residues and dephosphorylates threonine (Thr 14) and tyrosine (Tyr 15) residues (by CDC25 phosphatase) in the activation (ATP binding) loop. (omicsonline.org)
- This antibody does not cross-react with the corresponding phosphorylated residues of either JNK/SAPK or p38 MAP kinases. (cellsignal.com)
- Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Thr202/Tyr204 of human p44 MAP kinase. (cellsignal.com)
- Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. (ebi.ac.uk)
- A fewprotein kinases have dual specificity and phosphorylate threonine and tyrosine residues. (patentgenius.com)
- Adaptation of ERK2 is thus likely mediated by a phosphatase that can dephosphorylate phosphates from both threonine 176 and tyrosine 178 residues. (asm.org)
- The amino-terminal domain spans up to 125 amino acid residues and is involved in the formation of homotypic dimers among unphosphorylated STATs in resting cells. (hindawi.com)
- The dual-specificity phosphatase-6 (DUSP-6) is a member of dual-specificity protein phosphatase (DUSP) family, it can make residues of threonine and tyrosine dephosphorylate. (scitechnol.com)
- All DUSPs contain a common phosphatase domain with conserved aspartic acid, cysteine, and arginine residues forming the catalytic site. (scitechnol.com)
- MKP5, a new member of the MAP kinase phosphatase family, which selectively dephosphorylates stress-activated kinases. (uniprot.org)
- NMDA-mediated influx of Ca(2+) leads to activation of the Ca(2+) / Calmodulin -dependent phosphatase Calcineurin A (catalytic) that dephosphorylates and activates STEP [ 10 ]. (bio-rad.com)
- Dephosphorylates and deactivates p38 and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) (By similarity). (uniprot.org)
- Directly dephosphorylates CDK1 and stimulates its kinase activity. (hmdb.ca)
- Together these results indicate that MKP3(DUSP6) is the phosphatase that dephosphorylates ERK in the absence of FSH. (wsu.edu)
- The recombinant AtPTEN1 protein, like its homologs in animals, is an active phosphatase that dephosphorylates phosphotyrosine and phosphatidylinositol substrates. (plantcell.org)
- The Ca 2+ -bound calmodulin/calcineurin protein phosphatase complex dephosphorylates heavily phosphorylated, cytoplasmic NFAT, which, in turn, translocates into the nucleus and turns on various transcriptional programs. (jimmunol.org)
- Hypoxia stabilizes hypoxia inducible factor 1 (HIF-1), a transcription factor that regulates cell growth, proliferation and survival. (aacrjournals.org)
- While β- and γ-catenin play structural roles in the junctional complex, p120 regulates cadherin adhesive activity and trafficking (1-4). (cellsignal.com)
- The RAF/mitogen-activated protein kinase, extracellular signal-regulated kinase kinase (MEK)/ERK signaling cascade regulates multiple processes required for the proliferation and survival of normal cells. (pnas.org)
- 2001). „Identification of a docking groove on ERK and p38 MAP kinases that regulates the specificity of docking interactions" . (wikipedia.org)
- DUSP2 is a phosphatase that negatively regulates ERK activity . (nih.gov)
- YB-1 is a nucleic acid binding protein that regulates transcription and translation. (wsu.edu)
- p53 is a tumor suppressor that regulates cell cycle progression and the programmed cell death response to DNA damage ( 1 , 2 ). (aacrjournals.org)
- Hog1 regulates intracellular osmolarity in response to extracellular osmolarity and citric acid stress, Mpk1 regulates cell integrity and budding in response to mechanical changes at the cell wall/plasma membrane (with undefined input by Mpl1) and Smk1 regulates sporulation, being expressed only after meiosis has been initiated in response to carbon and nitrogen deprivation. (biologists.org)
- MKP-5 is a type III MKP that binds specifically to p38 and SPK/JNK and is found both in the cytoplasmic and nuclear regions of a cell. (wikipedia.org)
- Cytoplasmic protein tyrosine phosphatases such as SHP-1 also modulate BCR signaling ( 9 ) as exemplified by the severe B cell lymphopenia and autoantibody production of motheaten mice ( 10 ) that carry a debilitating mutation in SHP-1 ( 11 , 12 ). (rupress.org)
- Signal transducer and activator of transcription 3 (STAT3) is a latent cytoplasmic transcription factor, originally discovered as a transducer of signal from cell surface receptors to the nucleus. (hindawi.com)
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. (wikipedia.org)
- In an attempt to better understand COX-2-independent molecular mechanisms underlying the chemopreventive activity of celecoxib, we did global transcription profiling of celecoxib-treated COX-2-positive and COX-2-deficient colorectal cancer cell lines. (aacrjournals.org)
- Among the multiple molecular changes that are recorded during progression of this disease, aberrant activation of receptor tyrosine kinases (RTK) is often observed. (uni-wuerzburg.de)
- Here we report the identification of a large, multisubunit kinase (molecular mass approximately 700 kDa) that phosphorylates IkappaBalpha at S32 and S36. (semanticscholar.org)
- These findings suggest that chemical approaches to therapeutic cell reprogramming may be feasible and provide a powerful platform for analyzing molecular mechanisms of in vivo cell reprogramming. (biomedsearch.com)
- The details of Raf-1 activation are unclear, but our characterization of a second Ras-binding site in the cysteine-rich domain (CRD) and the involvement of both Ras-binding sites in effective Raf-1-mediated transformation provides insight into the molecular aspects and consequences of Ras-Raf interactions. (proteopedia.org)
- Lane 1: 1:5000, lane 2: 1:10000, lane 3: 1:20000 dilution of ERK2. (antibodies-online.com)
- Mitogenom-aktivirana proteinska kinaza 1 , takođe poznata kao MAPK1, p42MAPK, i ERK2 , je enzim koji je kod ljudi kodiran MAPK1 genom . (wikipedia.org)
- The MAP kinase ERK2 also plays critical roles during Dictyostelium development. (asm.org)
- erk2 − cells, starved for 8 h, exhibited a decrease in motility and a severe chemotaxis defect toward a cAMP gradient. (asm.org)
- erk2 − cells also display defective cytoskeletal remodeling in response to chemoattractant stimulation. (asm.org)
- In contrast, erk2 − cells, under the same condition, displayed multiple crown-like membranous protrusions, which were enriched not only in F-actin but also in myosin II ( 27 ). (asm.org)
- This aberrant structure, which was proposed to be less stable and unable to provide necessary traction force for cells to move, is believed to be the reason why erk2 − cells are less motile than wild-type cells ( 27 ). (asm.org)
- Currently, the phosphatase responsible for dephosphorylating ERK2 in Dictyostelium is unidentified. (asm.org)
- MAPK1 and MAPK3 (also known as ERK2 and ERK1, respectively) are members of the mitogen-activated protein kinase family. (biologists.org)
- ERK1 and ERK2 are key protein kinases that contribute to the Ras-Raf-MEK-ERK MAP kinase signalling module. (selleckchem.com)
- We analyzed miRNA profiles of three TNBC cell lines using an in vitro model of GR overexpression. (spandidos-publications.com)
- I/R-inducible manifestation of Rcan1 protein occurred primarily in astroglial cells and in an in vitro model of ischemia HGD treatment of main murine astrocyte ethnicities induced Rcan1-4 mRNA and protein manifestation. (bioentryplus.com)
- PTP-PEST is a ubiquitously expressed, cytosolic, mammalian protein tyrosine phosphatase (PTP) which exhibits high specific activity in vitro. (pubmedcentralcanada.ca)
- We initially identified a prominent 130-kDa tyrosine-phosphorylated protein in pervanadate-treated HeLa cell lysates which was preferentially dephosphorylated by PTP-PEST in vitro. (pubmedcentralcanada.ca)
- Furthermore, anisomycin, a potent stimulus of SAPK and p38 MAP kinase, also induced MKP-1 mRNA expression. (ahajournals.org)
- MKP-1, but not MKP-3, mRNA expression was 10-fold up-regulated in both mouse and human osteoblast cell lines within 30 min of Dex treatment and remained elevated for 24 h. (ox.ac.uk)
- We therefore investigated genome wide mRNA expression changes in PCa cells in response to Runx2. (biomedcentral.com)
- 3 MEK, the specific activator of ERK, is a dual-specificity protein kinase that phosphorylates both threonine and tyrosine regulatory sites in ERK. (ahajournals.org)
Signal transducer and activator of transcription1
- Tracheloside promotes keratinocyte proliferation through ERK1/2 stimulation. (selleckchem.com)
- The same effect was observed in the human melanoma cell line A375 after stimulation with FCS. (uni-wuerzburg.de)
- Similarly, Lyn up/up B cells show a heightened calcium flux in response to BCR stimulation. (rupress.org)
- These studies highlight the difficulty in maintaining tolerance in the face of chronic stimulation and emphasize the pivotal role of Lyn in B cell signaling. (rupress.org)
- Upon cell stimulation, DAG kinase converts DAG into phosphatidate, initiating the resynthesis of phosphatidylinositols and attenuating protein kinase C activity. (embl-heidelberg.de)
- Appropriate stimulation leads to expression in many human cells including macrophages, hepatocytes, smooth muscle, chondrocytes, cardiac myocytes, and a variety of cancer cells. (aacrjournals.org)
- Stimulation of TCR evokes Ca 2+ entry via Ca 2+ release-activated Ca 2+ (CRAC) channels ( 1 ). (jimmunol.org)
- Several downstream targets of p44/42 have been identified, including p90RSK (7) and the transcription factor Elk-1 (8,9). (cellsignal.com)
- Several downstream targets of ERK1/2 have been identified, including p90RSK and the transcription factor Elk-1. (ecmbiosciences.com)
- HIF-1 is both required and sufficient to induce lapatinib resistance as overexpression of stable HIF-1 in ERBB2-expressing cells blocks lapatinib-mediated effects and maintains ERBB2-downstream signaling under normoxic conditions. (nih.gov)
- We further identified YB-1 as a downstream target of ERK. (wsu.edu)
- The Raf-1 protein kinase is the best-characterized downstream effector of activated Ras. (proteopedia.org)
- Futhermore, the 5-ptases SHIP [SH2 (Src homology 2)-domain-containing inositol phosphatase] 2, SKIP (skeletal muscle- and kidney-enriched inositol phosphatase) and 72-5ptase (72 kDa 5-ptase)/Type IV/Inpp5e (inositol polyphosphate 5-phosphatase E) are implicated in negatively regulating insulin signalling and glucose homoeostasis in specific tissues. (biochemj.org)
- 2004). „Extracellular signal-regulated kinase 2 interacts with and is negatively regulated by the LIM-only protein FHL2 in cardiomyocytes" . (wikipedia.org)
- We demonstrate that, although MAPK1 is uniformly expressed in the lens epithelium, its deletion significantly reduces cell proliferation in the peripheral region, an area referred to as the lens germinative zone in which most active cell division occurs during normal lens development. (biologists.org)
- By contrast, cell proliferation in the central region is minimally affected by MAPK1 deletion. (biologists.org)
- Cell cycle regulators, including cyclin D1 and survivin, are downregulated in the germinative zone of the MAPK1-deficient lens. (biologists.org)
Protein tyrosine phosphatase su1
- VHR is only found in lymphoid and hematopoietic cells, and it inactivates the ERK1/2 and JNKs in T-cell receptors. (wikipedia.org)
- The expression of hormone receptors (ERα receptor and PRβ receptor) and the HER2 receptor are key biomarkers for breast cancer subtyping, prognosis, and therapy [ 1 ]. (biomedcentral.com)
- However, breast cancer cells express additional families of hormone receptors, especially the nuclear receptor superfamily [ 2 ]. (biomedcentral.com)
- Human oocytes and cumulus cells have GH receptors (GHRs) and can be directly influenced by GH, and GH can promote nuclear maturation of denuded human oocytes ( 2 - 4 ). (frontiersin.org)
- However, in prostate cancer cells, this is deregulated, allowing external stimuli to interact through membrane receptors with androgens and enhance their growth and proliferation. (aacrjournals.org)
- Alternative splicing of the receptors provides some degree of ligand specificity ( Itoh and Ornitz, 2004 ). (biologists.org)
- This subgroup of BC cells does not express the receptors for estrogen (ER), progesterone receptor (PR) and human epidermal growth factor 2 (HER2). (spandidos-publications.com)
- Adaptation responses to environmental cues are generated in cells by signaling initiated from cell receptors. (springer.com)
- Atorvastatin reduces the expression of prostaglandin E2 receptors in human carotid atherosclerotic plaques and monocytic cells: potential implications for plaque stabilization. (semanticscholar.org)
- Stromal-epithelial cell interactions also take place in the involved lymph nodes, where some carcinoma cells may attach and grow, in contrast with others that are not capable of establishing regional metastases. (springer.com)
- Metaanalysis comparison with the EGF effects in other cell types identified extensive similarities between responses in keratinocytes and in other epithelial cell types, but specific differences with the EGF effects in endothelial cells, and in transformed, oncogenic epithelial cell lines. (biomedcentral.com)
- GCs have multiple systemic effects that may influence bone metabolism but also directly affect osteoblasts by decreasing proliferation. (ox.ac.uk)
- Growth hormone (GH) is a peptide hormone secreted mainly by the anterior part of the pituitary gland and plays a critical role in cell growth, development, and metabolism throughout the body. (frontiersin.org)
- As a peptide hormone secreted mainly by the anterior part of the pituitary gland in a pulsatile manner, growth hormone (GH) plays a critical role in cell growth, development and metabolism throughout the body with multifunctional effects ranging far beyond the effect on linear growth ( 1 ). (frontiersin.org)