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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 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)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.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.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.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.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.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)Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.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.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.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.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.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.Mitogen-Activated Protein Kinase Kinases: A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.Mitogen-Activated Protein 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).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.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.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).)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 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.Acid Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.2.Mitogen-Activated Protein Kinase 3: A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.Protein 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.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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.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.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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Extracellular Signal-Regulated MAP Kinases: A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.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)HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Cell Line: Established cell cultures that have the potential to propagate indefinitely.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.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.Cell Line, Tumor: A cell line derived from cultured tumor cells.Glucose-6-Phosphatase: An enzyme that catalyzes the conversion of D-glucose 6-phosphate and water to D-glucose and orthophosphate. EC 3.1.3.9.Kinetics: The rate dynamics in chemical or physical systems.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.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.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.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.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 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.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.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.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.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)Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.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.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.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.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.Phosphorylase Phosphatase: An enzyme that deactivates glycogen phosphorylase a by releasing inorganic phosphate and phosphorylase b, the inactive form. EC 3.1.3.17.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.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.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.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.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)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.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.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.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.Receptor-Like Protein Tyrosine Phosphatases, Class 2: A subclass of receptor-like protein tryosine phosphatases that contain multiple extracellular immunoglobulin G-like domains and fibronectin type III-like domains. An additional memprin-A5-mu domain is found on some members of this subclass.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.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.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.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.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.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.Ethers, Cyclic: Compounds of the general formula R-O-R arranged in a ring or crown formation.Phosphatidate Phosphatase: A phosphomonoesterase involved in the synthesis of triacylglycerols. It catalyzes the hydrolysis of phosphatidates with the formation of diacylglycerols and orthophosphate. EC 3.1.3.4.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.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.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.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.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.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).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.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.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.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.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.