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.Glycogen Synthase Kinases: A class of protein-serine-threonine kinases that was originally found as one of the three types of kinases that phosphorylate GLYCOGEN SYNTHASE. Glycogen synthase kinases along with CA(2+)-CALMODULIN DEPENDENT PROTEIN KINASES and CYCLIC AMP-DEPENDENT PROTEIN KINASES regulate glycogen synthase activity.Glycogen Synthase: An enzyme that catalyzes the transfer of D-glucose from UDPglucose into 1,4-alpha-D-glucosyl chains. EC 2.4.1.11.GlycogenLithium Chloride: A salt of lithium that has been used experimentally as an immunomodulator.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.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)Liver Glycogen: Glycogen stored in the liver. (Dorland, 28th ed)beta Catenin: A multi-functional catenin that participates in CELL ADHESION and nuclear signaling. Beta catenin binds CADHERINS and helps link their cytoplasmic tails to the ACTIN in the CYTOSKELETON via ALPHA CATENIN. It also serves as a transcriptional co-activator and downstream component of WNT PROTEIN-mediated SIGNAL TRANSDUCTION PATHWAYS.Phosphatidylinositol 3-Kinases: Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.Proto-Oncogene Proteins c-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.Glycogen Phosphorylase: An enzyme that catalyzes the degradation of GLYCOGEN in animals by releasing glucose-1-phosphate from the terminal alpha-1,4-glycosidic bond. This enzyme exists in two forms: an active phosphorylated form ( PHOSPHORYLASE A) and an inactive un-phosphorylated form (PHOSPHORYLASE B). Both a and b forms of phosphorylase exist as homodimers. In mammals, the major isozymes of glycogen phosphorylase are found in muscle, liver and brain tissue.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.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.Aminophenols: Phenols substituted in any position by an amino group.MaleimidesProtein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Phosphorylases: A class of glucosyltransferases that catalyzes the degradation of storage polysaccharides, such as glucose polymers, by phosphorolysis in animals (GLYCOGEN PHOSPHORYLASE) and in plants (STARCH PHOSPHORYLASE).Axin Protein: A scaffolding protein that is a critical component of the axin signaling complex which binds to ADENOMATOUS POLYPOSIS COLI PROTEIN; GLYCOGEN SYNTHASE KINASE 3; and CASEIN KINASE I.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.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.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.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.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.Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER.Glucose: A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.tau Proteins: Microtubule-associated proteins that are mainly expressed in neurons. Tau proteins constitute several isoforms and play an important role in the assembly of tubulin monomers into microtubules and in maintaining the cytoskeleton and axonal transport. Aggregation of specific sets of tau proteins in filamentous inclusions is the common feature of intraneuronal and glial fibrillar lesions (NEUROFIBRILLARY TANGLES; NEUROPIL THREADS) in numerous neurodegenerative disorders (ALZHEIMER DISEASE; TAUOPATHIES).Wnt Proteins: Wnt proteins are a large family of secreted glycoproteins that play essential roles in EMBRYONIC AND FETAL DEVELOPMENT, and tissue maintenance. They bind to FRIZZLED RECEPTORS and act as PARACRINE PROTEIN FACTORS to initiate a variety of SIGNAL TRANSDUCTION PATHWAYS. The canonical Wnt signaling pathway stabilizes the transcriptional coactivator BETA CATENIN.Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).Indoles: Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Glucose-6-Phosphate: An ester of glucose with phosphoric acid, made in the course of glucose metabolism by mammalian and other cells. It is a normal constituent of resting muscle and probably is in constant equilibrium with fructose-6-phosphate. (Stedman, 26th ed)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.Cyclin-Dependent Kinase 5: A serine-threonine kinase that plays important roles in CELL DIFFERENTIATION; CELL MIGRATION; and CELL DEATH of NERVE CELLS. It is closely related to other CYCLIN-DEPENDENT KINASES but does not seem to participate in CELL CYCLE regulation.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.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.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Muscles: Contractile tissue that produces movement in animals.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.Androstadienes: Derivatives of the steroid androstane having two double bonds at any site in any of the rings.ChromonesTransfection: 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.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 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.Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.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)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.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.Muscle, Skeletal: A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.MorpholinesGlucosephosphatesRibosomal 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.Kinetics: The rate dynamics in chemical or physical systems.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Glycogen-Synthase-D Phosphatase: An enzyme that catalyzes the conversion of phosphorylated, inactive glycogen synthase D to active dephosphoglycogen synthase I. EC 3.1.3.42.Casein Kinase I: A casein kinase that was originally described as a monomeric enzyme with a molecular weight of 30-40 kDa. Several ISOENZYMES of casein kinase I have been found which are encoded by separate genes. Many of the casein kinase I isoenzymes have been shown to play distinctive roles in intracellular SIGNAL TRANSDUCTION.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 Line, Tumor: A cell line derived from cultured tumor cells.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.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.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.ThiadiazolesUridine Diphosphate Glucose: A key intermediate in carbohydrate metabolism. Serves as a precursor of glycogen, can be metabolized into UDPgalactose and UDPglucuronic acid which can then be incorporated into polysaccharides as galactose and glucuronic acid. Also serves as a precursor of sucrose lipopolysaccharides, and glycosphingolipids.beta-Transducin Repeat-Containing Proteins: A family of F-box domain proteins that contain sequences that are homologous to the beta subunit of transducin (BETA-TRANSDUCIN). They play an important role in the protein degradation pathway by becoming components of SKP CULLIN F-BOX PROTEIN LIGASES, which selectively act on a subset of proteins including beta-catenin and IkappaBbeta.Glycogen Storage Disease: A group of inherited metabolic disorders involving the enzymes responsible for the synthesis and degradation of glycogen. In some patients, prominent liver involvement is presented. In others, more generalized storage of glycogen occurs, sometimes with prominent cardiac involvement.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.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.Phosphoserine: The phosphoric acid ester of serine.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.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.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.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.PhosphoproteinsMitogen-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).Mice, Inbred C57BLPhosphorylase Kinase: An enzyme that catalyzes the conversion of ATP and PHOSPHORYLASE B to ADP and PHOSPHORYLASE A.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.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.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.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.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.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.Citrate (si)-Synthase: Enzyme that catalyzes the first step of the tricarboxylic acid cycle (CITRIC ACID CYCLE). It catalyzes the reaction of oxaloacetate and acetyl CoA to form citrate and coenzyme A. This enzyme was formerly listed as EC 4.1.3.7.Phosphatidylinositol 3-Kinase: A phosphatidylinositol 3-kinase that catalyzes the conversion of 1-phosphatidylinositol into 1-phosphatidylinositol 3-phosphate.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.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.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.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.Phosphorylase a: The active form of GLYCOGEN PHOSPHORYLASE that is derived from the phosphorylation of PHOSPHORYLASE B. Phosphorylase a is deactivated via hydrolysis of phosphoserine by PHOSPHORYLASE PHOSPHATASE to form PHOSPHORYLASE B.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Phosphothreonine: The phosphoric acid ester of threonine. Used as an identifier in the analysis of peptides, proteins, and enzymes.Time Factors: Elements of limited time intervals, contributing to particular results or situations.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.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.Lymphoid Enhancer-Binding Factor 1: A T-cell factor that plays an essential role in EMBRYONIC DEVELOPMENT.Ribosomal Protein S6 Kinases, 70-kDa: A family of ribosomal protein S6 kinases that are considered the major physiological kinases for RIBOSOMAL PROTEIN S6. Unlike RIBOSOMAL PROTEIN S6 KINASES, 90KDa the proteins in this family are sensitive to the inhibitory effects of RAPAMYCIN and contain a single kinase domain. They are referred to as 70kDa proteins, however ALTERNATIVE SPLICING of mRNAs for proteins in this class also results in 85kDa variants being formed.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.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.Lithium Compounds: Inorganic compounds that contain lithium as an integral part of the molecule.Wnt3 Protein: A Wnt protein subtype that plays a role in cell-cell signaling during EMBRYONIC DEVELOPMENT and the morphogenesis of the developing NEURAL TUBE. Defects in Wnt3 protein are associated with autosomal recessive tetra-AMELIA in humans.TCF Transcription Factors: A family of DNA-binding proteins that are primarily expressed in T-LYMPHOCYTES. They interact with BETA CATENIN and serve as transcriptional activators and repressors in a variety of developmental processes.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.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.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Casein Kinase Ialpha: A casein kinase I isoenzyme that plays a role in intracellular signaling pathways including the WNT SIGNALING PATHWAY, the CELL CYCLE, membrane trafficking, and RNA processing. Multiple isoforms of casein kinase I alpha exist and are due to ALTERNATIVE SPLICING.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)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.Wnt3A Protein: A Wnt protein subtype that plays a role in cell-cell signaling during EMBRYONIC DEVELOPMENT and the morphogenesis of the developing NEURAL TUBE.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.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.AMP-Activated Protein Kinases: Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Wnt Signaling Pathway: A complex signaling pathway whose name is derived from the DROSOPHILA Wg gene, which when mutated results in the wingless phenotype, and the vertebrate INT gene, which is located near integration sites of MOUSE MAMMARY TUMOR VIRUS. The signaling pathway is initiated by the binding of WNT PROTEINS to cells surface WNT RECEPTORS which interact with the AXIN SIGNALING COMPLEX and an array of second messengers that influence the actions of BETA CATENIN.Bromine Compounds: Inorganic compounds that contain bromine as an integral part of the molecule.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.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.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.Insulin Receptor Substrate Proteins: A structurally-related group of signaling proteins that are phosphorylated by the INSULIN RECEPTOR PROTEIN-TYROSINE KINASE. The proteins share in common an N-terminal PHOSPHOLIPID-binding domain, a phosphotyrosine-binding domain that interacts with the phosphorylated INSULIN RECEPTOR, and a C-terminal TYROSINE-rich domain. Upon tyrosine phosphorylation insulin receptor substrate proteins interact with specific SH2 DOMAIN-containing proteins that are involved in insulin receptor signaling.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Adenomatous Polyposis Coli Protein: A negative regulator of beta-catenin signaling which is mutant in ADENOMATOUS POLYPOSIS COLI and GARDNER SYNDROME.Glucosyltransferases: Enzymes that catalyze the transfer of glucose from a nucleoside diphosphate glucose to an acceptor molecule which is frequently another carbohydrate. EC 2.4.1.-.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.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.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.Low Density Lipoprotein Receptor-Related Protein-6: An LDL-receptor related protein that combines with cell surface FRIZZLED RECEPTORS to form WNT PROTEIN-binding receptors. The protein plays an important role in the WNT SIGNALING PATHWAY during EMBRYONIC DEVELOPMENT and in regulation of vascular cell proliferation.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Proteasome Endopeptidase Complex: A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.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.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.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.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.Immunoprecipitation: The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.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.Glycogen Debranching Enzyme System: 1,4-alpha-D-Glucan-1,4-alpha-D-glucan 4-alpha-D-glucosyltransferase/dextrin 6 alpha-D-glucanohydrolase. An enzyme system having both 4-alpha-glucanotransferase (EC 2.4.1.25) and amylo-1,6-glucosidase (EC 3.2.1.33) activities. As a transferase it transfers a segment of a 1,4-alpha-D-glucan to a new 4-position in an acceptor, which may be glucose or another 1,4-alpha-D-glucan. As a glucosidase it catalyzes the endohydrolysis of 1,6-alpha-D-glucoside linkages at points of branching in chains of 1,4-linked alpha-D-glucose residues. Amylo-1,6-glucosidase activity is deficient in glycogen storage disease type III.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.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.Thymidylate Synthase: An enzyme of the transferase class that catalyzes the reaction 5,10-methylenetetrahydrofolate and dUMP to dihydrofolate and dTMP in the synthesis of thymidine triphosphate. (From Dorland, 27th ed) EC 2.1.1.45.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.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.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.Wnt1 Protein: A proto-oncogene protein and member of the Wnt family of proteins. It is expressed in the caudal MIDBRAIN and is essential for proper development of the entire mid-/hindbrain region.Active Transport, Cell Nucleus: Gated transport mechanisms by which proteins or RNA are moved across the NUCLEAR MEMBRANE.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).Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Nitric Oxide Synthase Type I: A CALCIUM-dependent, constitutively-expressed form of nitric oxide synthase found primarily in NERVE TISSUE.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.Zebrafish Proteins: Proteins obtained from the ZEBRAFISH. Many of the proteins in this species have been the subject of studies involving basic embryological development (EMBRYOLOGY).Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.Eukaryotic Initiation Factor-2B: A guanine nucleotide exchange factor that acts to restore EUKARYOTIC INITIATION FACTOR-2 to its GTP bound form.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.Repressor Proteins: Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.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 enzymesImmunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.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.Nerve Tissue ProteinsCyclin D1: Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.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.Oximes: Compounds that contain the radical R2C=N.OH derived from condensation of ALDEHYDES or KETONES with HYDROXYLAMINE. Members of this group are CHOLINESTERASE REACTIVATORS.Pyruvate Kinase: ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.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.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.Ubiquitin: A highly conserved 76-amino acid peptide universally found in eukaryotic cells that functions as a marker for intracellular PROTEIN TRANSPORT and degradation. Ubiquitin becomes activated through a series of complicated steps and forms an isopeptide bond to lysine residues of specific proteins within the cell. These "ubiquitinated" proteins can be recognized and degraded by proteosomes or be transported to specific compartments within the cell.Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.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.Sirolimus: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.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.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.Muscle Proteins: The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN.Phosphotransferases (Alcohol Group Acceptor): A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.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.Flavonoids: A group of phenyl benzopyrans named for having structures like FLAVONES.Multivesicular Bodies: Endosomes containing intraluminal vesicles which are formed by the inward budding of the endosome membrane. Multivesicular bodies (MVBs) may fuse with other organelles such as LYSOSOMES or fuse back with the PLASMA MEMBRANE releasing their contents by EXOCYTOSIS. The MVB intraluminal vesicles released into the extracellular environment are known as EXOSOMES.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.NF-kappa B: Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.Microtubule-Associated Proteins: High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Glucose Transporter Type 4: A glucose transport protein found in mature MUSCLE CELLS and ADIPOCYTES. It promotes transport of glucose from the BLOOD into target TISSUES. The inactive form of the protein is localized in CYTOPLASMIC VESICLES. In response to INSULIN, it is translocated to the PLASMA MEMBRANE where it facilitates glucose uptake.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Adipocytes: Cells in the body that store FATS, usually in the form of TRIGLYCERIDES. WHITE ADIPOCYTES are the predominant type and found mostly in the abdominal cavity and subcutaneous tissue. BROWN ADIPOCYTES are thermogenic cells that can be found in newborns of some species and hibernating mammals.Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.Glycogen Storage Disease Type I: An autosomal recessive disease in which gene expression of glucose-6-phosphatase is absent, resulting in hypoglycemia due to lack of glucose production. Accumulation of glycogen in liver and kidney leads to organomegaly, particularly massive hepatomegaly. Increased concentrations of lactic acid and hyperlipidemia appear in the plasma. Clinical gout often appears in early childhood.Oncogene Protein v-akt: A viral oncoprotein originally isolated from a murine T CELL LYMPHOMA infected with the acutely transforming retrovirus AKT8. v-akt protein is the viral homologue of PROTO-ONCOGENE PROTEINS C-AKT.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.Phosphorylase b: The inactive form of GLYCOGEN PHOSPHORYLASE that is converted to the active form PHOSPHORYLASE A via phosphorylation by PHOSPHORYLASE KINASE and ATP.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Receptor, Insulin: A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE.Antimanic Agents: Agents that are used to treat bipolar disorders or mania associated with other affective disorders.Xenopus Proteins: Proteins obtained from various species of Xenopus. Included here are proteins from the African clawed frog (XENOPUS LAEVIS). Many of these proteins have been the subject of scientific investigations in the area of MORPHOGENESIS and development.Cyclin D: A cyclin subtype that is specific for CYCLIN-DEPENDENT KINASE 4 and CYCLIN-DEPENDENT KINASE 6. Unlike most cyclins, cyclin D expression is not cyclical, but rather it is expressed in response to proliferative signals. Cyclin D may therefore play a role in cellular responses to mitogenic signals.Molecular Weight: The sum of the weight of all the atoms in a molecule.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.1,4-alpha-Glucan Branching Enzyme: In glycogen or amylopectin synthesis, the enzyme that catalyzes the transfer of a segment of a 1,4-alpha-glucan chain to a primary hydroxy group in a similar glucan chain. EC 2.4.1.18.

Alzheimer's disease: clues from flies and worms. (1/3209)

Presenilin mutations give rise to familial Alzheimer's disease and result in elevated production of amyloid beta peptide. Recent evidence that presenilins act in developmental signalling pathways may be the key to understanding how senile plaques, neurofibrillary tangles and apoptosis are all biochemically linked.  (+info)

Axin prevents Wnt-3a-induced accumulation of beta-catenin. (2/3209)

When Axin, a negative regulator of the Wnt signaling pathway, was expressed in COS cells, it coeluted with glycogen synthase kinase-3beta (GSK-3beta), beta-catenin, and adenomatous polyposis coli protein (APC) in a high molecular weight fraction on gel filtration column chromatography. In this fraction, GSK-3beta, beta-catenin, and APC were co-precipitated with Axin. Although beta-catenin was detected in the high molecular weight fraction in L cells on gel filtration column chromatography, addition of conditioned medium expressing Wnt-3a to the cells increased beta-catenin in the low molecular weight fraction. However, Wnt-3a-dependent accumulation of beta-catenin was greatly inhibited in L cells stably expressing Axin. Axin also suppressed Wnt-3a-dependent activation of Tcf-4 which binds to beta-catenin and acts as a transcription factor. These results suggest that Axin forms a complex with GSK-3beta, beta-catenin, and APC, resulting in the stimulation of the degradation of beta-catenin and that Wnt-3a induces the dissociation of beta-catenin from the Axin complex and accumulates beta-catenin.  (+info)

Allosteric regulation of even-skipped repression activity by phosphorylation. (3/3209)

The Drosophila homeodomain protein Even-skipped (Eve) is a well characterized transcriptional repressor. Here, we show that Eve's ability to function in vitro is negatively regulated by phosphorylation. DNA-binding activity was unaffected by phosphorylation, but phosphorylated Eve was unable to interact with the TATA-binding protein (TBP), a known target for repression. Unexpectedly, phosphorylation of the Eve N terminus, which is dispensable for repression and TBP binding, was necessary and sufficient to inactivate Eve. LiCl, which specifically inhibits glycogen synthase kinase-3 (GSK-3), reduced Eve phosphorylation in nuclear extract and blocked inhibition of repression. In addition, Eve was phosphorylated and inactivated by purified GSK-3 beta plus casein kinase II. Our results suggest a novel mechanism of transcriptional control involving phosphorylation-induced allosteric interference with a repressive protein-protein interaction.  (+info)

Wingless signaling leads to an asymmetric response to decapentaplegic-dependent signaling during sense organ patterning on the notum of Drosophila melanogaster. (4/3209)

Wnt and Decapentaplegic cell signaling pathways act synergistically in their contribution to macrochaete (sense organ) patterning on the notum of Drosophila melanogaster. The Wingless-signaling pathway was ectopically activated by removing Shaggy activity (the homologue of vertebrate glycogen synthase kinase 3) in mosaics. Proneural activity is asymmetric within the Shaggy-deficient clone of cells and shows a fixed "polarity" with respect to body axis, independent of the precise location of the clone. This asymmetric response indicates the existence in the epithelium of a second signal, which we suggest is Decapentaplegic. Ectopic expression of Decapentaplegic induces extra macrochaetes only in cells which also receive the Wingless signal. Activation of Hedgehog signaling generates a long-range signal which can promote macrochaete formation in the Wingless activity domain. This signal depends upon decapentaplegic function. Autonomous activation of the Wingless signal response in cells causes them to attenuate or sequester this signal. Our results suggest a novel patterning mechanism which determines sense organ positioning in Drosophila.  (+info)

Xenopus axin interacts with glycogen synthase kinase-3 beta and is expressed in the anterior midbrain. (5/3209)

Axin is encoded by the fused locus in mice and is required for normal vertebrate axis formation. It has recently been shown that axin associates with APC, beta-catenin and glycogen synthase kinase-3 (GSK-3) in a complex that appears to regulate the level of cytoplasmic beta-catenin. We have identified the Xenopus homologue of axin through its interaction with GSK-3b. Xenopus axin (Xaxin) is expressed maternally and throughout early development with a low level of ubiquitous expression. Xaxin also shows remarkably high expression in the anterior mesencephalon adjacent to the forebrain-midbrain boundary.  (+info)

Regulation of beta-catenin signaling by the B56 subunit of protein phosphatase 2A. (6/3209)

Dysregulation of Wnt-beta-catenin signaling disrupts axis formation in vertebrate embryos and underlies multiple human malignancies. The adenomatous polyposis coli (APC) protein, axin, and glycogen synthase kinase 3beta form a Wnt-regulated signaling complex that mediates the phosphorylation-dependent degradation of beta-catenin. A protein phosphatase 2A (PP2A) regulatory subunit, B56, interacted with APC in the yeast two-hybrid system. Expression of B56 reduced the abundance of beta-catenin and inhibited transcription of beta-catenin target genes in mammalian cells and Xenopus embryo explants. The B56-dependent decrease in beta-catenin was blocked by oncogenic mutations in beta-catenin or APC, and by proteasome inhibitors. B56 may direct PP2A to dephosphorylate specific components of the APC-dependent signaling complex and thereby inhibit Wnt signaling.  (+info)

Differential activation of c-Jun NH2-terminal kinase and p38 pathways during FTY720-induced apoptosis of T lymphocytes that is suppressed by the extracellular signal-regulated kinase pathway. (7/3209)

FTY720 is a novel immunosuppressive drug derived from a metabolite from Isaria sinclairii that is known to induce apoptosis of rat splenic T cells. In this study, we examined the intracellular signaling pathway triggered by FTY720. Treatment of human Jurkat T lymphocytes with FTY720-induced apoptosis characterized by DNA fragmentation. The same treatment induced activation of protein kinases such as c-Jun NH2-terminal kinase (JNK), p38/CSBP (CSAID-binding protein), and a novel 36-kDa myelin basic protein (MBP) kinase, but not extracellular signal-regulated kinase (ERK). Pretreatment of Jurkat cells with DEVD-CHO blocked FTY720-induced DNA fragmentation as well as the activation of p38/CSBP. However, DEVD-CHO treatment failed to inhibit FTY720-induced activation of JNK and the 36-kDa MBP kinase. We have also demonstrated that activation of the ERK signaling pathway completely suppressed the FTY720-induced apoptotic process including activation of caspase 3 and activation of JNK and the 36-kDa MBP kinase. Furthermore, transient expression of constitutively active mitogen-activated protein kinase/ERK kinase (MEK) protected the cells from FTY720-induced cell death. The effect of MEK was canceled by coexpression of a mitogen-activated protein kinase phosphatase, CL100. These results indicate that JNK and p38 pathways are differentially regulated during FTY720-induced apoptosis and that activation of ERK pathway alone is sufficient to cancel the FTY720-induced death signal.  (+info)

Negative regulation of axis formation and Wnt signaling in Xenopus embryos by the F-box/WD40 protein beta TrCP. (8/3209)

Screening a maternal Xenopus expression library for activities that synergize with low levels of injected beta-catenin, we have isolated a clone encoding the C-terminal end of x-beta TrCP-2, a highly conserved protein belonging to the F-box/WD40 family of ubiquitin-ligase specificity factors. We show that x-beta TrCP-2 expression reduces dorsal axis formation in Xenopus embryos. A dominant negative mutant lacking the F-box triggers the opposite effect, inducing secondary axes and activating the expression of Wnt responsive genes in ectodermal explants. In light of the existence of beta TrCP transcripts associated with the vegetal cortex, we propose that beta TrCP plays a fundamental role in the establishment of the dorsal determinants during cortical rotation in Xenopus.  (+info)

Title: The Possible Involvement of Glycogen Synthase Kinase-3 (GSK-3) in Diabetes, Cancer and Central Nervous System Diseases. VOLUME: 17 ISSUE: 22. Author(s):Amar S., Belmaker R.H. and Agam G.. Affiliation:Beer-Sheba Mental Health Center PO Box 4600, Beer-Sheba ISRAEL.. Keywords:Glycogen synthase kinase 3-β, diabetes, cancer, CNS, bipolar disorder, schizophrenia, Wnt signaling, postmortem brain, lithium, inflammation. Abstract: Glycogen synthase kinase (GSK-3) is a key enzyme in multiple cell processes. Since many pharmacological compounds that have effects on common metabolic pathways may have uses in many different diseases, we review here the possible involvement of glycogen synthase kinase 3 in diabetes, cancer and CNS diseases. Moreover, diabetes has recently been strongly linked to CNS diseases such as schizophrenia and bipolar illness. GSK-3 is both directly and indirectly inhibited by lithium, a key compound for treatment of bipolar disorder. Several antipsychotic drugs also affect the ...
Active Aβ immunotherapy in Alzheimers disease (AD) induces removal of Aβ and phosphorylated tau (ptau). Glycogen Synthase Kinase (GSK)-3β is a kinase, responsible for phosphorylation of tau, activation of which can be induced by phosphorylated double-stranded RNA dependent protein kinase (pPKR). Using a post-mortem cohort of immunised AD cases, we investigated the effect of Abeta immunisation on GSK-3β expression and pPKR ...
A-kinase anchoring proteins (AKAPs) include a family of scaffolding proteins that target protein kinase A (PKA) and other signaling proteins to cellular compartments and thereby confine the activities of the associated proteins to distinct regions within cells. AKAPs bind PKA directly. The interaction is mediated by the dimerization and docking domain of regulatory subunits of PKA and the PKA-binding domain of AKAPs. Analysis of the interactions between the dimerization and docking domain and various PKA-binding domains yielded a generalized motif allowing the identification of AKAPs. Our bioinformatics and peptide array screening approaches based on this signature motif identified GSKIP (glycogen synthase kinase 3beta interaction protein) as an AKAP. GSKIP directly interacts with PKA and GSK3beta (glycogen synthase kinase 3beta). It is widely expressed and facilitates phosphorylation and thus inactivation of GSK3beta by PKA. GSKIP contains the evolutionarily conserved domain of unknown function ...
Glycogen Synthase Kinase 3 (GSK-‑3) is a serine/threonine protein kinase and one of several protein kinases, which phosphorylate glycogen synthase. It is also called Factor A (F A ) for its ability to activate the MgATP-dependent form of the protein phosphatase PP1 called F C (1-4)
The WNT signalling pathway controls many developmental processes and plays a key role in maintenance of intestine renewal and homeostasis. Glycogen Synthase Kinase 3 (GSK3) is an important component of the WNT pathway and is involved in regulating β-catenin stability and expression of WNT target genes. The mechanisms underpinning GSK3 regulation in this context are not completely understood, with some evidence suggesting this occurs through inhibitory N-terminal serine phosphorylation in a similar way to GSK3 inactivation in insulin signaling. To investigate this in a physiologically relevant context, we have analysed the intestinal phenotype of GSK3 knockin mice in which N-terminal serines 21/9 of GSK3α/β have been mutated to non-phosphorylatable alanine residues. We show that these knockin mutations have very little effect on overall intestinal integrity, cell lineage commitment, β-catenin localization or WNT target gene expression although a small increase in apoptosis at villi tips is ...
The transcription factor NF-E2-related factor 2 (Nrf2) is a master regulator of a genetic program, termed the phase 2 response, that controls redox homeostasis and participates in multiple aspects of physiology and pathology. Nrf2 protein stability is regulated by two E3 ubiquitin ligase adaptors, Keap1 and ß-TrCP, the latter of which was only recently reported. Here, two-dimensional (2D) gel electrophoresis and site-directed mutagenesis allowed us to identify two serines of Nrf2 that are phosphorylated by glycogen synthase kinase 3ß (GSK-3ß) in the sequence DSGISL. Nuclear magnetic resonance studies defined key residues of this phosphosequence involved in docking to the WD40 propeller of ß-TrCP, through electrostatic and hydrophobic interactions. We also identified three arginine residues of ß-TrCP that participate in Nrf2 docking. Intraperitoneal injection of the GSK-3 inhibitor SB216763 led to increased Nrf2 and heme oxygenase-1 levels in liver and hippocampus. Moreover, mice with ...
Recent Research Presentations (Personally presented):. Natural compounds isolated from diverse plants and their usefulness for combating fatal diseases like human oral cancer. BELMSBR, Mar 29-30, 2017 at NOU, Baripada, India. (Invited Talk). Application of Synthetic/ Natural Compounds for Combating Oral Cancer: Role of an Enzyme Glycogen Synthase Kinase 3 beta. ICFCS, Mar 16-18, 2017 at CUJ, Ranchi, India. (Invited Lecture) Awakening GSK3beta (glycogen synthase kinase 3beta), the resting conqueror, to fight against human oral epithelial cancer. World Congress on Cancer Research & Therapy on Nov 21-23, 2016 at Miami, FL, USA. (Invited Talk). Aggressiveness of human oral cancer and the role of glycogen synthase kinase 3 isoforms α/β signaling. 12th Asian Clinical Oncology Society Conference (ACOS- 2016), April 8-10, New Delhi, India. Aggressiveness of tobacco mediated human oral cancer and the role of glycogen synthase kinase 3 isoforms α/β signaling. International Conference on Environmental ...
Exacerbated hippocampal activity has been associated to critical modifications of the intracellular signaling pathways. We have investigated rapid hippocampal adaptive responses induced by maximal electroshock seizure (MES). Here, we demonstrate that abnormal and exacerbated hippocampal activity induced by MES triggers specific and temporally distinct patterns of phosphorylation of extracellular signal-related kinase (ERK), mammalian target of rapamycin complex (mTORC) and Akt/glycogen synthase kinase-3 (Akt/GSK-3) pathways in the mouse hippocampus. While the ERK pathway is transiently activated, the mTORC1 cascade follows a rapid inhibition followed by a transient activation. This rebound of mTORC1 activity leads to the selective phosphorylation of p70S6K, which is accompanied by an enhanced phosphorylation of the ribosomal subunit S6. In contrast, the Akt/GSK-3 pathway is weakly altered. Finally, MES triggers a rapid upregulation of several plasticity-associated genes as a consequence exacerbated
Phosphatidylinositol-3 kinase (PI3-K) and protein kinase B (Akt) activation not only stimulate NO production, but they also inhibit glycogen synthase kinase-3β (GSK3β) (8). Similarly, activation of canonical Wnt signaling inactivates GSK3β (9). Wnts are secreted glycoproteins known to regulate hematopoiesis and stem cell function (9). In the unstimulated cell, GSK3β phosphorylates and accelerates degradation of HIF-1α and β-catenin (9,10). Inhibition of GSK3β leads to cytosolic accumulation and nuclear translocation of these transcription factors in a manner that increases EPC survival, proliferation, differentiation, mobilization, and adhesion (11-13). EPCs pretreated with GSK inhibitors or EPCs that are genetically modified to overexpress VEGF or inactive GSK3β enhance vasculogenesis, augment reendothelialization, and reduce neointimal formation (11-13).. Diabetes is associated with reduced endothelial NO bioavailability and PI3-K/Akt activity, and EPCs are defective and reduced in ...
Background Inhibition of glycogen synthase kinase-3 (GSK-3) improves the efficiency of embryonic stem (ES) cell derivation from various strains of mice and rats, as well as dramatically promotes ES cell self-renewal potential. β-catenin has been reported to be involved in the maintenance of self-renewal of ES cells through TCF dependent and independent pathway. But the intrinsic difference between ES cell lines from different species and strains has not been characterized. Here, we dissect the mechanism of GSK-3 inhibition by CHIR99021 in mouse ES cells from refractory mouse strains. Methodology/Principal Findings We found that CHIR99021, a GSK-3 specific inhibitor, promotes self-renewal of ES cells from recalcitrant C57BL/6 (B6) and BALB/c mouse strains through stabilization of β-catenin and c-Myc protein levels. Stabilized β-catenin promoted ES self-renewal through two mechanisms. First, β-catenin translocated into the nucleus to maintain stem cell pluripotency in a lymphoid-enhancing factor/T
Abstract Background Glycogen synthase kinase-3 (GSK-3) is a ubiquitously expressed serine/threonine (Ser/Thr) kinase comprising two isoforms, GSK-3 and GSK-3. procedures. Nevertheless, the specificity of these antibodies in immunocytochemistry offers not really been resolved in any fine detail. ResultsTaking benefit of gene silencing technology, we analyzed the specificity of many in a commercial sense obtainable anti-phosphorylated GSK-3 antibodies. We display that antibodies elevated to peptides made up of the phosphorylated Ser21/9 epitope crossreact with mysterious antigens that are extremely indicated by mitotic cells and that primarily localise to spindle poles. In addition, two antibodies elevated to peptides made up of the phosphorylated Tyr279/216 epitope recognise an mysterious proteins at focal connections, and a third antibody recognises a proteins discovered in Ki-67-positive cell nuclei. While the phosphorylated Ser9/21 GSK-3 antibodies also recognise additional protein whose ...
The phosphorylation of Amyloid Precursor Protein (APP) at Thr668 plays a key role in APP metabolism that is highly relevant to AD. The c-Jun-N-terminal kinase (JNK), glycogen synthase kinase-3β (GSK-3β) and cyclin-dependent kinase 5 (Cdk5) can all be responsible for this phosphorylation. These kinases are activated by excitotoxic stimuli fundamental hallmarks of AD. The exposure of cortical neurons to a high dose of NMDA (100 μM) for 30-45 led to an increase of P-APP Thr668. During NMDA stimulation APP hyperphosphorylation has to be assigned to GSK-3β activity, since addition of L803-mts, a substrate competitive inhibitor of GSK-3β reduced APP phosphorylation induced by NMDA. On the contrary, inhibition of JNK and Cdk5 with D-JNKI1 and Roscovitine respectively did not prevent NMDA-induced P-APP increase. These data show a tight connection, in excitotoxic conditions, between APP metabolism and the GSK-3β signaling pathway.
TY - JOUR. T1 - Glycogen synthase kinase-3β inhibition enhances myelination in preterm newborns with intraventricular hemorrhage, but not recombinant Wnt3A. AU - Dohare, Preeti. AU - Cheng, Bokun. AU - Ahmed, Ehsan. AU - Yadala, Vivek. AU - Singla, Pranav. AU - Thomas, Sunisha. AU - Kayton, Robert. AU - Ungvari, Zoltan. AU - Ballabh, Praveen. PY - 2018/10. Y1 - 2018/10. N2 - Intraventricular hemorrhage (IVH) in preterm infants results in reduced proliferation and maturation of oligodendrocyte progenitor cells (OPCs), and survivors exhibit reduced myelination and neurological deficits. Wnt signaling regulates OPC maturation and myelination in a context dependent manner. Herein, we hypothesized that the occurrence of IVH would downregulate Wnt signaling, and that activating Wnt signaling by GSK-3β inhibition or Wnt3A recombinant human protein (rh-Wnt3A) treatment might promote maturation of OPCs, myelination of the white matter, and neurological recovery in premature rabbits with IVH. These ...
Neural stem cells (NSCs) hold great potential for the treatment of neurodegenerative diseases. However, programmed cell death (PCD) provoked by the harsh conditions evident in the diseased brain greatly undermines the potential of NSCs. Currently, the mechanisms of PCD that effect NSCs remain largely unknown. We have previously reported that hippocampal neural stem (HCN) cells derived from the adult rat brain undergo autopahgic cell death (ACD) following insulin withdrawal without hallmarks of apoptosis despite their normal apoptotic capabilities. In this study, we demonstrate that glycogen synthase kinase 3β (GSK-3β) induces ACD in insulin-deprived HCN cells. Both pharmacological and genetic inactivation of GSK-3β significantly decreased ACD, while activation of GSK-3β increased autophagic flux and caused more cell death without inducing apoptosis following insulin withdrawal. In contrast, knockdown of GSK-3α barely affected ACD, lending further support to the critical role of GSK-3β.
The graphic displays domains and Protease cut sites on the protein sequence. Drag your mouse right/left over the graphic. Use the selection boxes on the right to select which annotations to view simultaneously. Combine annotation with multiple checkmarks.. ...
ABSTRACTGlycogen synthase kinase-3 (GSK3) is a serine/threonine protein kinase firstly identified as a regulator of glycogen synthesis. Recently, it has been proved to be a key regulator of the immune reaction. In the present study, a GSK3 homolog gene (designated as EsGSK3) was cloned from Chinese
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Purpose: Evasion from chemotherapy-induced apoptosis due to p53 loss strongly contributes to drug resistance. Identification of specific targets for the treatment of drug-resistant p53-null tumors would therefore increase the effectiveness of cancer therapy.. Experimental Design: By using a kinase-directed short hairpin RNA library and HCT116p53KO drug-resistant colon carcinoma cells, glycogen synthase kinase 3 beta (GSK3B) was identified as a target whose silencing bypasses drug resistance due to loss of p53. p53-null colon cancer cell lines with different sets of mutations were used to validate the role of GSK3B in sustaining resistance and to characterize cell death mechanisms triggered by chemotherapy when GSK3B is silenced. In vivo xenograft studies were conducted to confirm resensitization of drug-resistant cells to chemotherapy upon GSK3 inhibition. Colon cancer samples from a cohort of 50 chemotherapy-treated stage II patients were analyzed for active GSK3B expression.. Results: ...
Glycogen synthase kinase 3 has evolutionarily conserved roles in cell signaling and metabolism and is a recognized drug target in neurological pathologies, most prominently bipolar disorder. More recently it has been suggested that GSK3 may be a target for the treatment of trypanosomatid parasite infections, e.g. w
rIPC [remote IPC (ischaemic preconditioning)] has been shown to invoke potent myocardial protection in animal studies and recent clinical trials. Although the important role of PI3K (phosphoinositide 3-kinase)/Akt activation in the cardioprotection afforded by local IPC is well described, our understanding of the intracellular signalling of rIPC remains incomplete. We therefore examined the hypothesis that the myocardial protection afforded by rIPC is mediated via the PI3K/Akt/GSK3β (glycogen synthase kinase 3β) signalling pathway, activation of which is associated with nuclear accumulation of β-catenin. rIPC was induced in mice using four cycles of 5 min of ischaemia and 5 min of reperfusion of the hindlimb using a torniquet. This led to reduced infarct size (19±4% in rIPC compared with 39±7% in sham; P,0.05), improved functional recovery and reduced apoptosis after global I/R (ischaemia/reperfusion) injury using a Langendorff-perfused mouse heart model. These effects were reversed by ...
Kirschenbaum F, Hsu SC, Cordell B, McCarthy JV. Substitution of a glycogen synthase kinase-3beta phosphorylation site in presenilin 1 separates presenilin function from beta-catenin signaling ...
GSK3B / GSK3 Beta (C-Terminus) antibody | P49841 | Glycogen synthase kinase-3 beta, GSK-3 beta, Serine/threonine-protein kinase GSK3B, Gsk 3beta, GSK3 beta, GSK3beta
Development of protein kinase inhibitors is a focus of many drug discovery programs. A major problem, however, is the limited specificity of the commonly used adenosine triphosphate-competitive inhibitors and the weak inhibition of the more selective substrate-competitive inhibitors. Glycogen synthase kinase-3 (GSK-3) is a promising drug target for treating neurodegenerative disorders, including Alzheimers disease (AD), but most GSK-3 inhibitors have not reached the clinic. We describe a new type of GSK-3 inhibitor, L807mts, that acts through a substrate-to-inhibitor conversion mechanism that occurs within the catalytic site of the enzyme. We determined that L807mts was a potent and highly selective GSK-3 inhibitor with reasonable pharmacological and safety properties when tested in rodents. Treatment with L807mts enhanced the clearance of β-amyloid loads, reduced inflammation, enhanced autophagic flux, and improved cognitive and social skills in the 5XFAD AD mouse model. This new modality of ...
1o6l_A mol:protein length:337 RAC-BETA SERINE/THREONINE PROTEIN KINASE KVTMNDFDYLKLLGKGTFGKVILVREKATGRYYAMKILRKEVIIAKDEVAHTVTESRVL QNTRHPFLTALKYAFQTHDRLCFVMEYANGGELFFHLSRERVFTEERARFYGAEIVSAL EYLHSRDVVYRDIKLENLMLDKDGHIKITDFGLCKEGISDGATMKTFCGTPEYLAPEVL EDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHERLFELILMEEIRFPRTLSPEAKSLL AGLLKKDPKQRLGGGPSDAKEVMEHRFFLSINWQDVVQKKLLPPFKPQVTSEVDTRYFD DEFTAQSITITPPDRYDSLGLLELDQREEQEMFEDFDYIADW >1o6l_C mol:protein length:10 GLYCOGEN SYNTHASE KINASE-3 BETA GRPRTTSFAE >1o6l_C mol:protein length:10 GLYCOGEN SYNTHASE KINASE-3 BETA GRPRTTSFAE ...
國璽幹細胞與安南醫院心臟內科部長李聰明教授共同合作,由李教授以冠狀動脈左前降枝結紮手術(ligation of the left anterior descending artery, LAD)模擬心肌梗塞後的心律不整模式,結合國璽幹細胞的「醫藥級脂肪幹細胞製劑生產技術平台」製造的幹細胞,成功證實調控PI3K/Akt/GSK-3β訊息傳遞路徑,有助於降低發生心肌梗塞後所造成的心律不整。研究成果刊登於Journal of Molecular and Cellular ...
Glycogen synthase kinase-3 (GSK-3) is a widely expressed and highly conserved serine/threonine protein kinase encoded by two genes that generate two related proteins: GSK-3α and GSK-3β. Mice lacking a functional GSK-3α gene were engineered in our laboratory; they are viable and display insulin sensitivity. In this study, we have characterized brain functions of GSK-3α KO mice by using a well-established battery of behavioral tests together with neurochemical and neuroanatomical analysis. Similar to the previously described behaviours of GSK-3β+/-mice, GSK-3α mutants display decreased exploratory activity, decreased immobility time and reduced aggressive behavior. However, genetic inactivation of the GSK-3α gene was associated with: decreased locomotion and impaired motor coordination, increased grooming activity, loss of social motivation and novelty; enhanced sensorimotor gating and impaired associated memory and coordination. GSK-3α KO mice exhibited a deficit in fear conditioning, however
Phosphatidylinositol-3 kinase (PI3-K) and protein kinase B (Akt) activation not only stimulate NO production, but they also inhibit glycogen synthase kinase-3β (GSK3β) (8). Similarly, activation of canonical Wnt signaling inactivates GSK3β (9). Wnts are secreted glycoproteins known to regulate hematopoiesis and stem cell function (9). In the unstimulated cell, GSK3β phosphorylates and accelerates degradation of HIF-1α and β-catenin (9,10). Inhibition of GSK3β leads to cytosolic accumulation and nuclear translocation of these transcription factors in a manner that increases EPC survival, proliferation, differentiation, mobilization, and adhesion (11-13). EPCs pretreated with GSK inhibitors or EPCs that are genetically modified to overexpress VEGF or inactive GSK3β enhance vasculogenesis, augment reendothelialization, and reduce neointimal formation (11-13).. Diabetes is associated with reduced endothelial NO bioavailability and PI3-K/Akt activity, and EPCs are defective and reduced in ...
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Structure of the asymmetric unit of the human lamin A/C fragment. "Structural basis for lamin assembly at the molecular level", Nature Communications (2019). "Conversion of cell-survival activity of Akt into apoptotic death of cancer cells by two mutations on the BIM BH3 domain", Cell. Death. Dis. (2015). "Development of Akt-activated GSK3β inhibitory peptide", Biochem. Biophys. Res. Commun. (2013). "Role of CK1 in GSK3beta-mediated phosphorylation and degradation of Snail", Oncogene (2010). "The role of the Ser/Thr cluster in the phosphorylation of PPPSP motif in Wnt coreceptors", Biochem. Biophys. Res. Commun. (2009). ...
Alzheimers disease (AD) is one of the most common neurological disorders with vast reaching worldwide prevalence. Research attempts to decipher whats happening to the human mind have shown that...
Several kinases implicated in multiple signaling pathways elicit conflicting responses depending on the cellular context. One such kinase is glycogen synthase kinase 3 (GSK3), a cytoplasmic serine-threonine kinase that is involved in insulin signaling and metabolic regulation, as well as in Wnt signaling and the specification of cell fates during embryonic development (3). GSK3 appears in two highly homologous and ubiquitously expressed forms, GSK3α and GSK3β (4). The insulin and Wnt signaling pathways differentially regulate GSK3α/β resulting in distinct downstream events (5), but how they accomplish this is not clear. The recent report of the crystal structure of GSK3β by Dajani and colleagues in Cell (6), together with a biochemical study of GSK3_ by Frame et al. in Molecular Cell (7), reveal how GSK3 selectively regulates different downstream targets according to which signaling pathway is activated.. GSK3 is unusual among kinases in that its normal activity in the cytoplasm is blocked ...
Glycogen synthase kinase 3 (GSK-3) in its active state complexes with APC and AXIN to suppress phosphorylation of β-catenin, which then gets degraded via the proteasome. GSK-3 becomes inactivated through the PI3K/AKT pathway when the cell receives signals like growth factors, cytokines, or insulin. WNT signaling can also inactivate GSK-3 through Dsh. Inactivation of GSK-3 leads to gene expression, cell survival, and cell proliferation.. Click on the poster below to view the interactive version.. ...
Dysregulation of glycogen synthase kinase (GSK-3β) is implicated in the pathophysiology of many diseases, including type-2 diabetes, stroke, Alzheimers, and others. A multistage virtual screening strategy designed so as to overcome known caveats arising from the considerable flexibility of GSK-3β yielded, from among
As the major downstream target of mammalian target of rapamycin complex 1 (mTORC1), S6K phosphorylates multiple downstream substrates including S6, eIF4B, and GSK3 (glycogen synthase kinase 3) to regulate various key cellular processes including protein synthesis, cell size, cell proliferation (18-21), and cell migration (22). However, the biochemical and biological functions of different S6K family proteins including S6K1 (which consists of the p70S6K1 and p85S6K1 isoforms) and S6K2 (also known as p56S6K2) are relatively undefined (23). In keeping with a possible oncogenic role for S6K kinases, bioinformatics analysis indicated that both S6K1 and S6K2 were amplified in multiple human cancers, especially in breast cancers (fig. S2, A and B). The amplification of S6K1 and S6K2 appeared to be mutually exclusive in breast cancers (fig. S2C), suggesting possibly redundant functions of S6K1 and S6K2. Structurally, p85S6K1 shared a high degree of homology in amino acid sequence with p56S6K2, except ...
The AlphaLISA® SureFire® Ultra™ p-GSK-3β (Ser9) assay kit is an immunoassay for quantitative detection of endogenous GSK-3β (phosphorylated at Ser9) in cellular lysates.
Of the discovery of GSK3 (glycogen synthase kinase 3) inhibitors there has been no end. I first came across it as a target it about 1997, and even then, once I
Abstract Background Glycogen synthase kinase-3 (GSK-3) is a ubiquitously expressed serine/threonine (Ser/Thr) kinase comprising two isoforms, GSK-3 and GSK-3. procedures. Nevertheless, the specificity of these antibodies in immunocytochemistry offers not really been resolved in any fine detail. ResultsTaking benefit of gene silencing technology, we analyzed the specificity of many in a commercial sense obtainable anti-phosphorylated GSK-3 antibodies. We display that antibodies elevated to peptides made up of the phosphorylated Ser21/9 epitope crossreact with mysterious antigens that are extremely indicated by mitotic cells and that primarily localise to spindle poles. In addition, two antibodies elevated to peptides made up of the phosphorylated Tyr279/216 epitope recognise an mysterious proteins at focal connections, and a third antibody recognises a proteins discovered in Ki-67-positive cell nuclei. While the phosphorylated Ser9/21 GSK-3 antibodies also recognise additional protein whose ...
Enhancing β-cell proliferation is a major goal for type 1 and type 2 diabetes research. Unraveling the network of β-cell intracellular signaling pathways that promote β-cell replication can provide the tools to address this important task. In a previous Perspectives in Diabetes article, we discussed what was known regarding several important intracellular signaling pathways in rodent β-cells, including the insulin receptor substrate/phosphatidylinositol-3 kinase/Akt (IRS-PI3K-Akt) pathways, glycogen synthase kinase-3 (GSK3) and mammalian target of rapamycin (mTOR) S6 kinase pathways, protein kinase Cζ (PKCζ) pathways, and their downstream cell-cycle molecular targets, and contrasted that ample knowledge to the small amount of complementary data on human β-cell intracellular signaling pathways ...
In the prior funding period, we demonstrated that conditional elimination of the Glycogen Synthase Kinase-3s (GSK-3s), a and ?, in the embryonic nervous system...
Glycogen synthase kinase-3 (GSK-3) is ubiquitously expressed throughout the brain and involved in vital molecular pathways such as cell survival and synaptic reorganization and has emerged as a potential drug target for brain diseases. A causal role for GSK-3, in particular the brain-enriched GSK-3β isoform, has been demonstrated in neurodegenerative diseases such as Alzheimers and Huntingtons, and in psychiatric diseases. ...
TWS119 is a glycogen synthase kinase-3β inhibitor with an IC50 of 30 nM. Find all the information about TWS119 for cell signaling research.
Background Despite recent desire for glycogen synthase kinase-3b (GSK-3b) like a target for the treatment of mood disorders there has been very little work related to these ailments within the upstream signaling molecules that regulate this kinase as well as downstream focuses on. genes. Improved manifestation and function of Wnt2 was confirmed by secondary actions. […]. ...
AB - We compute the NSVZ beta functions for N = 1 four-dimensional quiver theoriesarising from D-brane probes on singularities, complete with anomalousdimensions, for a large set of phases in the corresponding duality tree. Whilethese beta functions are zero for D-brane probes, they are non-zero in thepresence of fractional branes. As a result there is a non-trivial RG behavior.We apply this running of gauge couplings to some toric singularities such asthe cones over Hirzebruch and del Pezzo surfaces. We observe the emergence instring theory, of ``Duality Walls, a finite energy scale at which the numberof degrees of freedom becomes infinite, and beyond which Seiberg duality doesnot proceed. We also identify certain quiver symmetries as T-duality-likeactions in the dual holographic theory ...
GSK-3阻害剤(経路に合図することの標的を妨げる)がいろいろな分析のために使われて、いくつかは臨床試験に入りました。そして、それは新しいガン療法です。
Plasmid pLKO.1-GSK3β-#2 from Dr. Alex Tokers lab contains the insert GSK3B and is published in Mol Cancer Res. 2009 Mar;7(3):425-32. Epub 2009 Mar 3. This plasmid is available through Addgene.
Kalio chloridas GSK is a medicine available in a number of countries worldwide. A list of US medications equivalent to Kalio chloridas GSK is available on the Drugs.com website.
Christoph Westphal to move to Longwood Fund, leaving GSK Dr Christoph Westphal, President of SR One, is to leave GlaxoSmithKline later in 2011 to focus on external business interests, primarily the
In Saccharomyces cerevisiae, nutrient levels control multiple cellular processes. Cells lacking the SNF1 gene cannot express glucose-repressible genes and do not accumulate the storage polysaccharide glycogen. The impaired glycogen synthesis is due to maintenance of glycogen synthase in a hyperphosphorylated, inactive state. In a screen for second site suppressors of the glycogen storage defect of snf1 cells, we identified a mutant gene that restored glycogen accumulation and which was allelic with PHO85, which encodes a member of the cyclin-dependent kinase family. In cells with disrupted PHO85 genes, we observed hyperaccumulation of glycogen, activation of glycogen synthase, and impaired glycogen synthase kinase activity. In snf1 cells, glycogen synthase kinase activity was elevated. Partial purification of glycogen synthase kinase activity from yeast extracts resulted in the separation of two fractions by phenyl-Sepharose chromatography, both of which phosphorylated and inactivated glycogen ...
Full Text - The rapid and efficient clearance of apoptotic germ cells (GCs) by Sertoli cells (SCs) is important for spermatogenesis. High mitochondrial activity in phagocytes is critical for continued clearance of apoptotic cells. However, the underlying molecular mechanism is poorly understood. Glycogen synthase kinase-3α (GSK3α) is a protein kinase that participates in the regulation of mitochondrial activity. Immunohistochemistry evidenced the predominant presence of the Ser21 phosphorylation GSK3α (inactivation) signal in SCs. Heat shock-induced apoptosis of GCs and dephosphorylation of GSK3α in SCs is a perfect model to investigate the role of GSK3α in phagocytic action. The number of apoptotic GCs was significantly lower in GSK3α inhibitor pre-treated mice with HS compared to normal control. In vitro phagocytosis assays shown that the phagocytic activity in GSK3α activated SCs was downregulated, while GSK3α inhibitor supplementation restored this process. Moreover, GSK3α activation
"Regulation of glycogen synthase kinase-3 during bipolar mania treatment". Bipolar Disord. 12 (7): 741-52. doi:10.1111/j.1399- ... Yildiz A, Guleryuz S, Ankerst DP, Ongür D, Renshaw PF (2008). "Protein kinase C inhibition in the treatment of mania: a double- ... 2 (3): 136-146. ISSN 1723-8617. PMC 1525098 . PMID 16946919.. *^ Nusslock, Robin; Young, Christina B.; Damme, Katherine S. F. ( ... 65 (3): 255-63. doi:10.1001/archgenpsychiatry.2007.43. PMID 18316672.. *^ Brietzke E, Stertz L, Fernandes BS, Kauer-Sant'anna M ...
"Evidence for Irreversible Inhibition of Glycogen Synthase Kinase-3 by Tideglusib" (PDF). The Journal of Biological Chemistry. ... ATP-competitive glycogen synthase kinase 3 (GSK-3) inhibitor.. Potential applications[edit]. Tideglusib is under investigation ... "Evidence for Irreversible Inhibition of Glycogen Synthase Kinase-3 by Tideglusib". Journal of Biological Chemistry. 287 (2): ... As of 2017 it was undergoing Phase IIa[2] and IIb clinical trials.[3][4][5][6] The first trial to be published (in English) was ...
"Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3". Science. 275 (5308): 1930-4. doi:10.1126/science.275.5308. ... mitogen-activated protein kinase p38 binding. • FK506 binding. • transcriptional activator activity, RNA polymerase II distal ... Porter CM, Havens MA, Clipstone NA (Feb 2000). "Identification of amino acid residues and protein kinases involved in the ... Transcriptional activity of NFATc1 is enhanced by the Pim-1 kinase". Journal of Immunology. 168 (4): 1524-7. doi:10.4049/ ...
Glycogen synthase kinase-3β, NF-κB signaling, and tumorigenesis of human osteosarcoma. „J Natl Cancer Inst". 104 (10), s. 749- ... The cyclin-dependent kinase inhibitor SCH 727965 (dinacliclib) induces the apoptosis of osteosarcoma cells. „Mol Cancer Ther". ... Clinical and biological significance of PIM1 kinase in osteosarcoma. „J Orthop Res", Dec 2015. DOI: 10.1002/jor.23134. PMID: ... Transforming growth factor-beta as a key molecule triggering the expression of versican isoforms v0 and v1, hyaluronan synthase ...
... in insulin-induced glycogen synthase kinase 3 inactivation. Characterization of dominant-negative mutant of PKB". J. Biol. Chem ... stimulates glycogen synthase, and glucose 6 phosphate may inhibit the phosphorylation of glycogen synthase by cyclic AMP- ... The role of glucose 6-phosphate in glycogen synthase: High blood glucose concentration causes an increase in intracellular ... Phosphorylation of src tyrosine kinase (pronounced "sarc") by C-terminal Src kinase (Csk) induces a conformational change in ...
"Temporal correlation of the memory deficit with Alzheimer-like lesions induced by activation of glycogen synthase kinase-3". ... 117 (3): 659-71. doi:10.1172/JCI29562. PMC 1797603. PMID 17318264.. *^ a b Hahnen E, Eyüpoglu IY, Brichta L, Haastert K, ... M (y) 2; H (ni) 3 M (y) 9; H (ny) D (y) 11 R (y) 17; H (ny) MC 23, 24; M (y) 25; H (v) 26, 27, 28, 29 ... 19 (3): 895-907. doi:10.3233/JAD-2010-1284. PMID 20157245.. *^ Byun CJ, Seo J, Jo SA, Park YJ, Klug M, Rehli M, Park MH, Jo I ( ...
"A-kinase anchoring protein AKAP220 binds to glycogen synthase kinase-3beta (GSK-3beta ) and mediates protein kinase A-dependent ... Glycogen synthase kinase 3 beta, also known as GSK3B, is an enzyme that in humans is encoded by the GSK3B gene. In mice, the ... "Entrez Gene: GSK3B glycogen synthase kinase 3 beta". Pal R, Bondar VV, Adamski CJ, Rodney GG, Sardiello M (2017). "Inhibition ... Glycogen synthase kinase-3 (GSK-3) is a proline-directed serine-threonine kinase that was initially identified as a ...
Glycogen synthase kinase-3 alpha is an enzyme that in humans is encoded by the GSK3A gene. Glycogen synthase kinase 3-alpha EC ... "Entrez Gene: GSK3A glycogen synthase kinase 3 alpha". Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput ... Glycogen synthase kinase 3 GRCh38: Ensembl release 89: ENSG00000105723 - Ensembl, May 2017 GRCm38: Ensembl release 89: ... Ali A, Hoeflich KP, Woodgett JR (Aug 2001). "Glycogen synthase kinase-3: properties, functions, and regulation". Chemical ...
Ali A, Hoeflich KP, Woodgett JR (2002). "Glycogen synthase kinase-3: properties, functions, and regulation". Chem. Rev. 101 (8 ... "Protein kinase C-associated kinase (PKK), a novel membrane-associated, ankyrin repeat-containing protein kinase". J. Biol. Chem ... Protein kinase C beta type is an enzyme that in humans is encoded by the PRKCB gene. Protein kinase C (PKC) is a family of ... PRKCB1 has been shown to interact with RIPK4, beta adrenergic receptor kinase, PDLIM5 and GNB2L1. Protein kinase C GRCh38: ...
Ali A, Hoeflich KP, Woodgett JR (2002). "Glycogen synthase kinase-3: properties, functions, and regulation". Chem. Rev. 101 (8 ... Protein kinase C gamma type is an enzyme that in humans is encoded by the PRKCG gene. Protein kinase C (PKC) is a family of ... specifically require this kinase. Knockout studies in mice also suggest that this kinase may be involved in neuropathic pain ... This protein kinase is expressed solely in the brain and spinal cord and its localization is restricted to neurons. It has been ...
Martín CP, Vázquez J, Avila J, Moreno FJ (2002). "P24, a glycogen synthase kinase 3 (GSK 3) inhibitor". Biochim. Biophys. Acta ... identification of sites targeted by different kinases". J. Biol. Chem. 282 (40): 29531-9. doi:10.1074/jbc.M703466200. PMID ... 2006). "Interaction of TPPP/p25 protein with glyceraldehyde-3-phosphate dehydrogenase and their co-localization in Lewy bodies ...
Forde, J. E.; Dale, T. C. (2007-08-01). "Glycogen synthase kinase 3: a key regulator of cellular fate". Cellular and molecular ... glycogen synthase kinase 3 (GSK3-an enzyme that has been found to be related to hyperphosphorylation of tau protein) - ... 52 (3): 381-387. doi:10.1111/j.1532-5415.2004.52109.x. PMID 14962152. Carusone SC, Goldsmith CH, Smieja M, Loeb M (April 2006 ... 126 (Pt 3): 590-597. doi:10.1093/brain/awg059. ISSN 0006-8950. PMID 12566280. Lus, G.; Nelis, E.; Jordanova, A.; Löfgren, A.; ...
"Mitochondrial hexokinase II promotes neuronal survival and acts downstream of glycogen synthase kinase-3". The Journal of ... kinase activity. • glucose binding. • catalytic activity. • protein binding. • fructokinase activity. • ATP binding. • ... Another critical function for OMM-bound HK2 is mediation of cell survival.[8][9] Activation of Akt kinase maintains HK2-VDAC ... In a similar mechanism, the pro-apoptotic creatine kinase binds and opens VDAC in the absence of HK2.[8] An alternative model ...
Glycogen Synthase Kinase 3 Beta (GSK3B) GSK3B is a protein kinase that regulates transcription factors and microtubules. As ... "GSK3B - Glycogen synthase kinase-3 beta - Homo sapiens (Human) - GSK3B gene & protein". www.uniprot.org. Retrieved 2017-04-23. ... Serine/Threonine-Protein Kinase PAK 1 (PAK 1), and DNA Replication Factor Cdt1 (CDT1). KIAA1211L is associated with depression ... protein kinases assay, two hybrid, and confocal microscopy experiments. KIAA1211L protein is also predicted to interact with ...
"The integrin-linked kinase regulates the cyclin D1 gene through glycogen synthase kinase 3beta and cAMP-responsive element- ... Glycogen synthase kinase three beta, GSK3β, causes Cyclin D degradation by inhibitory phosphorylation on threonine 286 of the ... Diehl JA, Cheng M, Roussel MF, Sherr CJ (November 1998). "Glycogen synthase kinase-3β regulates cyclin D1 proteolysis and ... Rho family GTPases, integrin linked kinase and focal adhesion kinase (FAK) activate cyclin D gene in response to integrin. ...
Activation of the Wnt pathway inhibits glycogen synthase kinase 3 beta (GSK3B). When the Wnt pathway is not active, GSK3 beta ... Second generation inhibitors are able to bind to the ATP-binding motif on the kinase domain of the mTOR core protein itself and ... Saitoh M, Pullen N, Brennan P, Cantrell D, Dennis PB, Thomas G (May 2002). "Regulation of an activated S6 kinase 1 variant ... De P, Miskimins K, Dey N, Leyland-Jones B (Aug 2013). "Promise of rapalogues versus mTOR kinase inhibitors in subset specific ...
This interaction appears to be regulated by glycogen synthase kinase 3 beta. Mutations in emerin cause X-linked recessive Emery ... 12 (3): 254-9. doi:10.1038/ng0396-254. PMID 8589715. Manilal S, Nguyen TM, Sewry CA, Morris GE (Jun 1996). "The Emery-Dreifuss ... 267 (3): 709-14. doi:10.1006/bbrc.1999.2023. PMID 10673356. Zhang Q, Skepper JN, Yang F, Davies JD, Hegyi L, Roberts RG, ... 303 (3): 764-70. doi:10.1016/s0006-291x(03)00415-7. PMID 12670476. Berk JM, Simon DN, Jenkins-Houk CR, Westerbeck JW, Grønning- ...
2006). "Novel glycogen synthase kinase 3 and ubiquitination pathways in progressive myoclonus epilepsy". Hum. Mol. Genet. 14 ( ...
2007). "Glycogen synthase kinase-3 phosphorylates CdGAP at a consensus ERK 1 regulatory site". J. Biol. Chem. 282 (6): 3624-31 ... 2010). "A human MAP kinase interactome". Nat. Methods. 7 (10): 801-5. doi:10.1038/nmeth.1506. PMC 2967489 . PMID 20936779. ...
"Mitochondrial hexokinase II promotes neuronal survival and acts downstream of glycogen synthase kinase-3". The Journal of ... As an isoform of hexokinase and a member of the sugar kinase family, HK2 catalyzes the rate-limiting and first obligatory step ... Activation of Akt kinase maintains HK2-VDAC coupling, which subsequently prevents cytochrome c release and apoptosis, though ... In a similar mechanism, the pro-apoptotic creatine kinase binds and opens VDAC in the absence of HK2. An alternative model ...
Gustafson MP, Welcker M, Hwang HC, Clurman BE (2006). "Zcchc8 is a glycogen synthase kinase-3 substrate that interacts with RNA ... 338 (3): 1359-67. doi:10.1016/j.bbrc.2005.10.090. PMID 16263084. Beausoleil SA, Villén J, Gerber SA, et al. (2006). "A ...
Glycogen synthase kinase 3 (GSK3) seems to be over-expressed in most cancer cells. GSK3 is involved in promoter activation ... Viral proteins like viral thymidine kinase can be used for specific targeting of a drug. By introducing a prodrug only ... kinase/Akt, heat shock protein 90, and mammalian target of rapamycin in transformed NK cells". J. Immunol. 174 (9): 5261-9. doi ... 10 (3): 281-7. doi:10.1016/S1074-7613(00)80028-X. PMID 10204484. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda ...
Cross, D. A.; Alessi, D. R.; Cohen, P; Andjelkovich, M; Hemmings, B. A. (1995). "Inhibition of glycogen synthase kinase-3 by ... insulin mediated by protein kinase B". Nature. 378 (6559): 785-9. doi:10.1038/378785a0. PMID 8524413. Alessi, D. R.; Corrie, J ...
"Presenilin 1 regulates beta-catenin-mediated transcription in a glycogen synthase kinase-3-independent fashion". The Journal of ... 37 (3): 254-77. doi:10.1210/er.2015-1146. PMID 27159876. Slattery ML, Folsom AR, Wolff R, Herrick J, Caan BJ, Potter JD (April ... 88 (3-4): 264-5. doi:10.1159/000015534. PMID 10828605. Duval A, Rolland S, Tubacher E, Bui H, Thomas G, Hamelin R (July 2000 ... 277 (3): 1884-91. doi:10.1074/jbc.M110248200. PMID 11711551. Graham TA, Ferkey DM, Mao F, Kimelman D, Xu W (December 2001). " ...
... in insulin-induced glycogen synthase kinase 3 inactivation. Characterization of dominant-negative mutant of PKB". J. Biol. Chem ... It was found that an enzyme, named phosphorylase kinase and Mg-ATP were required to phosphorylate glycogen phosphorylase by ... Cyclin-dependent kinases (CDKs) are serine-threonine kinases which regulate progression through the eukaryotic cell cycle. CDKs ... Most phosphorylation is carried out by a single superfamily of protein kinases that share a conserved kinase domain. Protein ...
Glycogen synthase. *Debranching enzyme. *Branching enzyme. *1,3-Beta-glucan synthase. *Ceramide glucosyltransferase ... doi:10.1016/S1367-5931(02)00390-3. PMID 12470740.. *^ Nilsson I, Kelleher DJ, Miao Y, Shao Y, Kreibich G, Gilmore R, von Heijne ... The sugar Glc3Man9GlcNAc2 (where Glc=Glucose, Man=Mannose, and GlcNAc=N-acetylglucosamine) is attached to an asparagine (Asn) ... They are labelled "Type I" if the defective gene is for an enzyme involved in the assembly or transfer of the Glc3Man9GlcNAc2- ...
Phosphorylase Kinase Deficiency; Beta Enolase Deficiency; Lactate Dehydrogenase Deficiency; Glycogen Synthase Deficiency ... Glycogen Storage Disease Type I; Glycogen Storage Disease Type II; Glycogen Storage Disease Type III; Glycogen Storage Disease ... Glycogen Storage Disease Type II; Glycogen Storage Disease Type III; Glycogen Storage Disease Type IV; Glycogen Storage Disease ... Type IV; Glycogen Storage Disease Type V; Glycogen Storage Disease Type VI; Glycogen Storage Disease Type VII; Glycogen Storage ...
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... is a serine/threonine protein kinase and one of several protein kinases, which phosphorylate glycogen synthase. It is also ... is a serine/threonine protein kinase and one of several protein kinases, which phosphorylate glycogen synthase. It is also ... Protein Kinases Information. Applications: Protein Phosphatases & Kinases. * Properties and Usage Unit Definition. One unit is ... 1X NEBuffer™ for Protein Kinases (PK) 50 mM Tris-HCl 10 mM MgCl2 0.1 mM EDTA 2 mM DTT 0.01% Brij 35 (pH 7.5 @ 25°C) ...
Expression and function of glycogen synthase kinase-3 in human hair follicles.. Yamauchi K1, Kurosaka A. ... and inhibition of glycogen synthase kinase-3 (GSK-3) increases beta-catenin concentration in the cytoplasm. To examine the ... A GSK-3 inhibitor, BIO, promoted the growth of human outer root sheath cells, which could be cultured for up to four passages. ... Contrary to GSK-3beta, GSK-3 alpha was widely expressed throughout the follicles when immunostained with a specific antibody, ...
... in the same manner as glycogen synthase. In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta- ... by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN ... contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen ... Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt ...
Contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen ... by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), CTNNB1/beta-catenin, APC and AXIN1. Requires primed ... Regulates glycogen metabolism in liver, but not in muscle. May also mediate the development of insulin resistance by regulating ... Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt ...
AKT or protein kinase B (PKB), and glycogen synthase kinase (GSK)-3β (the phosphatidylinositol 3-kinase/Akt/GSK-3β pathway) (1 ... Summers SA, Kao AW, Kohn AD, Backus GS, Roth RA, Pessin JE, Birnbaum MJ: The role of glycogen synthase kinase 3beta in insulin- ... Nikoulina SE, Ciaraldi TP, Mudaliar S, Carter L, Johnson K, Henry RR: Inhibition of glycogen synthase kinase 3 improves insulin ... Eldar-Finkelman H, Krebs EG: Phosphorylation of insulin receptor substrate 1 by glycogen synthase kinase 3 impairs insulin ...
... glycogen synthase kinase 3 beta), Authors: Dinesh Kumar Thotala, Eugenia M Yazlovitskaya. Published in: Atlas Genet Cytogenet ... GSK3B Kinase-like_dom_sf Prot_kinase_dom Protein_kinase_ATP_BS Ser/Thr_kinase_AS ... Glycogen synthase kinase-3 beta; a new target in pancreatic cancer?. Garcea G, Manson MM, Neal CP, Pattenden CJ, Sutton CD, ... GSK3B (glycogen synthase kinase 3 beta). Written. 2010-04. Dinesh Kumar Thotala, Eugenia M Yazlovitskaya. ...
We show that homozygous deletion of glycogen synthase kinase (GSK) 3β (GSK3β−/−) bypasses senescence induced by mutant RasV12 ... Homozygous deletion of glycogen synthase kinase 3β bypasses senescence allowing Ras transformation of primary murine ... Homozygous deletion of glycogen synthase kinase 3β bypasses senescence allowing Ras transformation of primary murine ... Homozygous deletion of glycogen synthase kinase 3β bypasses senescence allowing Ras transformation of primary murine ...
In addition, DHM increased glycogen synthase kinase-3 beta phosphorylation in a dose- and time-dependent manner, which may be ... Additionally, mice were treated with either 5 or 10 mg/kg DHM for a total of 13 d (3 d before the start of MPTP, during MPTP ... The present study demonstrated that DHM is a potent neuroprotective agent for DA neurons by modulating the Akt/GSK-3β pathway, ... Male C57BL/6 mice were intraperitoneally injected with 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 d to induce PD ...
Protein target information for Glycogen synthase kinase-3 beta (human). Find diseases associated with this biological target ...
Glycogen Synthase Kinase 3 (GSK-3) and Its Inhibitors: Drug Discovery and Development. Ana Martinez (Editor), Ana Castro ( ... Structures of Glycogen Synthase Kinase 3. 5. Kinase-Kinase and Site-Site Interactions in the Phosphorylation of Tau by GSK-3. ... 7. Glycogen Synthase Kinase-3: A Target for Novel Mood Disorder Treatments. 8. GSK3 and Stem Cells. 9. Glycogen Synthase Kinase ... Glycogen Synthase Kinase 3 (GSK-3) and Its Inhibitors: Drug Discovery and Development. ...
1997) Regulation of protein kinase B and glycogen synthase kinase-3 by insulin and beta-adrenergic agonists in rat epididymal ... 1996) Regulation of mitochondrial pyruvate dehydrogenase activity by tau protein kinase I/glycogen synthase kinase 3beta in ... OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase. Proc Natl ... 1992) Glycogen synthase kinase-3 and the Alzheimer-like state of microtubule-associated protein tau. FEBS Lett 314:315-321. ...
Glycogen Synthase Kinase-3β Haploinsufficiency Mimics the Behavioral and Molecular Effects of Lithium. W. Timothy OBrien, ... De Sarno P, Li X, Jope RS (2002) Regulation of Akt and glycogen synthase kinase-3beta phosphorylation by sodium valproate and ... Hoeflich KP, Luo J, Rubie EA, Tsao MS, Jin O, Woodgett JR (2000) Requirement for glycogen synthase kinase-3beta in cell ... Song L, De Sarno P, Jope RS (2002) Central role of glycogen synthase kinase-3beta in endoplasmic reticulum stress-induced ...
Glycogen synthase kinase-3β (GSK3β) suppresses tumor progression by downregulating multiple oncogenic pathways including Wnt ... is a physiologic inhibitor of c-RAF kinase and nuclear factor κB signaling that represses tumor invasion and metastasis. ... Raf kinase inhibitor protein RKIP enhances signaling by glycogen synthase kinase-3β Cancer Res. 2011 Feb 15;71(4):1334-43. doi ... Glycogen synthase kinase-3β (GSK3β) suppresses tumor progression by downregulating multiple oncogenic pathways including Wnt ...
... is a serine-threonine kinase that exists as two isoforms, alpha and beta, encoded by separate genes. Phosphorylation targets ... Glycogen synthase kinase-3 (GSK-3) is a serine-threonine kinase that exists as two isoforms, alpha and beta, encoded by ... Isolation and chromosomal mapping of human glycogen synthase kinase-3 alpha and -3 beta encoding genes Genome. 1998 Oct;41(5): ... Two clones, 220 and 285 kb in size, containing the complete GSK-3 alpha coding sequence, and two clones, 365 and 285 kb in size ...
... and animal behavioral studies showing that serotonin regulates the activation states of brain glycogen synthase kinase-3 (GSK3 ... and animal behavioral studies showing that serotonin regulates the activation states of brain glycogen synthase kinase-3 (GSK3 ... Jope, R. S., and Johnson, G. V. W. (2004). The glamour and gloom of glycogen synthase kinase-3. Trends Biochem. Sci. 29, 95-102 ... Glycogen synthase kinase-3 is an intermediate modulator of serotonin neurotransmission. Abigail M. Polter and Xiaohua Li* ...
Ascl1a/Dkk/β-catenin signaling pathway is necessary and glycogen synthase kinase-3β inhibition is sufficient for zebrafish ... Ascl1a/Dkk/β-catenin signaling pathway is necessary and glycogen synthase kinase-3β inhibition is sufficient for zebrafish ... Ascl1a/Dkk/β-catenin signaling pathway is necessary and glycogen synthase kinase-3β inhibition is sufficient for zebrafish ... Ascl1a/Dkk/β-catenin signaling pathway is necessary and glycogen synthase kinase-3β inhibition is sufficient for zebrafish ...
Glycogen synthase kinase-3 beta in complex with 3-indolyl-4-arylmaleimide inhibitor. ...
... a serine/threonine-protein kinase has been implicated in a number of diseases including st ... Over activity of Glycogen synthase kinase-3β (GSK-3β), ... Over activity of Glycogen synthase kinase-3β (GSK-3β), a serine ... Insight into glycogen synthase kinase-3β inhibitory activity of phyto-constituents from Melissa officinalis: in silico studies ... Iwaloye, O., Elekofehinti, O.O., Oluwarotimi, E.A. et al. Insight into glycogen synthase kinase-3β inhibitory activity of phyto ...
Glycogen synthase from rabbit skeletal muscle. Amino acid sequence at the sites phosphorylated by glycogen synthase kinase-3, ... Role of glycogen synthase kinase-3 in cell fate and epithelial-mesenchymal transitions. Cells Tissues Organs 2007;185:73-84pmid ... Glycogen synthase kinase (GSK) 3β is a serine/threonine kinase originally identified as an enzyme that phosphorylates and ... Glycogen Synthase Kinase-3β Inhibition Ameliorates Cardiac Parasympathetic Dysfunction in Type 1 Diabetic Akita Mice. ...
Tolnay, M., Juang, Y.-T., and Tsokos, G. C. (2002) Protein kinase A enhances, whereas glycogen synthase kinase-3β inhibits, the ... Here we report the O-GlcNAc perturbations in response to inhibition of glycogen synthase kinase-3 (GSK-3), a pivotal kinase ... Gould, T. D., and Manji, H. K. (2005) Glycogen synthase kinase-3: a putative molecular target for lithium mimetic drugs. ... Zhang, F., Phiel, C. J., Spece, L., Gurvich, N., and Klein, P. S. (2003) Inhibitory phosphorylation of glycogen synthase kinase ...
Glycogen synthase kinase-3 (GSK-3) regulates various intracellular signaling pathways; its role in TGF-β(1) -induced ... The effect of GSK-3 inhibition on α-sm-actin expression was similar in fibroblasts from individuals with and without COPD. ... Neither smad, NF-κB, nor ERK1/2 were involved in the inhibitory actions of GSK-3 inhibition by SB126763 on myofibroblast ... Moreover, silencing of GSK-3 by siRNA or pharmacological inhibition by CT/CHIR99021 fully inhibited the TGF-β(1) -induced ...
  • To analyse the organisation of these two genes, a YAC library was screened by polymerase chain reaction, using primers specific for human GSK-3 alpha and GSK-3 beta cDNA. (nih.gov)
  • GSK-3 has been highly conserved during evolution, and homolog genes have been identified in virtually every eukaryotic genome investigated. (acris-antibodies.com)
  • Two GSK-3 genes (α and β) have been cloned in mammals and these kinase homologues show strong sequence conservation within their catalytic domain ( 14 ). (aacrjournals.org)
  • Together, these data suggest that the CK2 and GSK-3 pathways regulate AKT/PI3K signaling in leukemia via two complementary mechanisms: a) direct phosphorylation of PTEN and b) transcriptional regulation of PI3K-promoting genes. (elsevier.com)
  • GSK-3 mRNA and protein are involved in transcribing a variety of genes that are involved in the progression of pathology. (currentenzymeinhibition.com)
  • Recent studies have suggested the involvement of GSK-3β in the pathogenesis and treatment target of DA-associated neuropsychiatric disorders, which has led to consider GSK-beta as one of the candidate genes for those disorders. (elsevier.com)
  • GSK-3β genes are likely to be involved in mechanisms underlying attention deficit hyperactivity disorder (ADHD). (elsevier.com)
  • Although it seems specifically kill transformed and cancer cells originally ( 3 ), concerns about TRAIL toxicity in humans emerged with recent reported adverse effects on primary cultures of human tissues ( 6 ) or normal prostate-derived cells ( 5 ). (aacrjournals.org)
  • The lower GSK-3β expression generated by Aβ immunotherapy shows evidence of a modification of the signalling pathway induced by GSK-3β leading to the overall reduction of tau, supporting the contention that in humans, GSK-3β unifies Aβ and tau-related neuropathology. (soton.ac.uk)
  • There are three variants of p90rsk in humans, rsk 1-3. (wikipedia.org)
  • Here we investigate the effects of 2 chemically distinct inhibitors of GSK-3β, TDZD-8 and SB216763, on the circulatory failure and the organ injury and dysfunction associated with hemorrhagic shock. (ovid.com)
  • Axil bound not only to GSK-3β but also to β-catenin, and the GSK-3β-binding site of Axil was distinct from the β-catenin-binding site. (asm.org)
  • Male C57BL/6 mice were intraperitoneally injected with 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 d to induce PD. (nature.com)
  • Additionally, mice were treated with either 5 or 10 mg/kg DHM for a total of 13 d (3 d before the start of MPTP, during MPTP administration (7 d) and 3 d after the end of MPTP). (nature.com)
  • We found that lithium alters specific behaviors in a manner that is paralleled in mice lacking one copy of Gsk-3 β. (jneurosci.org)
  • VP3.36 (3 mg/kg) significantly enhanced working memory and spatial object recognition in C57BL/6J mice. (operamedphys.org)
  • Homozygous disruption of the GSK-3β locus in mice results in embryonic lethality during mid-gestation. (wikipedia.org)