Protein Kinase C: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.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.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.Calcium-Calmodulin-Dependent Protein Kinases: A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Mitogen-Activated Protein Kinases: A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.MAP Kinase Signaling System: An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.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.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.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Mitogen-Activated Protein Kinase 1: A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.Protein Kinase C-alpha: A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.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.Protein Kinase C-delta: A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.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.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.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.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.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Protein Kinase C-epsilon: A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.Protein Kinase C beta: PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.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.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Cyclic GMP-Dependent Protein Kinases: A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.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.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.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.Kinetics: The rate dynamics in chemical or physical systems.Cell Line: Established cell cultures that have the potential to propagate indefinitely.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.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.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.Calcium-Calmodulin-Dependent Protein Kinase Type 2: A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.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).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.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.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.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.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.Ribosomal Protein S6 Kinases: A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.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.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.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.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.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.PhosphoproteinsProto-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.MAP Kinase Kinase 4: A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.DiglyceridesPhorbol 12,13-Dibutyrate: A phorbol ester found in CROTON OIL which, in addition to being a potent skin tumor promoter, is also an effective activator of calcium-activated, phospholipid-dependent protein kinase (protein kinase C). Due to its activation of this enzyme, phorbol 12,13-dibutyrate profoundly affects many different biological systems.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.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.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.Isoquinolines: A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)Staurosporine: An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine: A specific protein kinase C inhibitor, which inhibits superoxide release from human neutrophils (PMN) stimulated with phorbol myristate acetate or synthetic diacylglycerol.Phorbol Esters: Tumor-promoting compounds obtained from CROTON OIL (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.MaleimidesCreatine 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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.DNA-Activated Protein Kinase: A serine-threonine protein kinase that, when activated by DNA, phosphorylates several DNA-binding protein substrates including the TUMOR SUPPRESSOR PROTEIN P53 and a variety of TRANSCRIPTION FACTORS.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.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.Cyclic AMP-Dependent Protein Kinase Type II: A cyclic AMP-dependent protein kinase subtype primarily found in particulate subcellular fractions. They are tetrameric proteins that contain two catalytic subunits and two type II-specific regulatory subunits.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.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.AMP Deaminase: An enzyme that catalyzes the deamination of AMP to IMP. EC 3.5.4.6.Phosphotransferases (Alcohol Group Acceptor): A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.3-Phosphoinositide-Dependent Protein Kinases: Highly conserved protein-serine threonine kinases that phosphorylate and activate a group of AGC protein kinases, especially in response to the production of the SECOND MESSENGERS, phosphatidylinositol 3,4,-biphosphate (PtdIns(3,4)P2) and phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3).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.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.Flavonoids: A group of phenyl benzopyrans named for having structures like FLAVONES.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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.rho-Associated Kinases: A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.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.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.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.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 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.Androstadienes: Derivatives of the steroid androstane having two double bonds at any site in any of the rings.Mitogen-Activated Protein Kinase 8: A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.Cell Line, Tumor: A cell line derived from cultured tumor cells.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.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.I-kappa B Kinase: A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.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.Carbazoles: Benzo-indoles similar to CARBOLINES which are pyrido-indoles. In plants, carbazoles are derived from indole and form some of the INDOLE ALKALOIDS.Adenosine Monophosphate: Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.Thymidine Kinase: An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21.Phosphoserine: The phosphoric acid ester of serine.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.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Alkaloids: Organic nitrogenous bases. Many alkaloids of medical importance occur in the animal and vegetable kingdoms, and some have been synthesized. (Grant & Hackh's Chemical Dictionary, 5th ed)Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Ribosomal Protein S6 Kinases, 90-kDa: A family of ribosomal protein S6 kinases that are structurally distinguished from RIBOSOMAL PROTEIN S6 KINASES, 70-KDA by their apparent molecular size and the fact they contain two functional kinase domains. Although considered RIBOSOMAL PROTEIN S6 KINASES, members of this family are activated via the MAP KINASE SIGNALING SYSTEM and have been shown to act on a diverse array of substrates that are involved in cellular regulation such as RIBOSOMAL PROTEIN S6 and CAMP RESPONSE ELEMENT-BINDING PROTEIN.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.MAP Kinase Kinase Kinase 1: A 195-kDa MAP kinase kinase kinase with broad specificity for MAP KINASE KINASES. It is found localized in the CYTOSKELETON and can activate a variety of MAP kinase-dependent pathways.1-Phosphatidylinositol 4-Kinase: An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.CDC2-CDC28 Kinases: A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.ChromonesDiacylglycerol Kinase: An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.Aurora Kinases: A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.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.MAP Kinase Kinase 2: A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.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.Imidazoles: Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).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.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.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Cell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.MorpholinesCattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Myosin-Light-Chain Kinase: An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.8-Bromo Cyclic Adenosine Monophosphate: A long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase.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.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.Calcium-Calmodulin-Dependent Protein Kinase Kinase: A regulatory calcium-calmodulin-dependent protein kinase that specifically phosphorylates CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE TYPE 1; CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE TYPE 2; CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE TYPE 4; and PROTEIN KINASE B. It is a monomeric enzyme that is encoded by at least two different genes.Colforsin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.Death-Associated Protein Kinases: A family of calcium/calmodulin-dependent PROETIN-SERINE-THREONINE KINASES. They are ubiquitously expressed in adult and embryonic mammalian tissues, and their functions are tightly related to the early stages of eukaryotic programmed cell death.Benzophenanthridines: Compounds of four rings containing a nitrogen. They are biosynthesized from reticuline via rearrangement of scoulerine. They are similar to BENZYLISOQUINOLINES. Members include chelerythrine and sanguinarine.Cyclic GMP: Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)Cyclic GMP-Dependent Protein Kinase Type I: A cyclic GMP-dependent protein kinase subtype that is expressed in SMOOTH MUSCLE tissues and plays a role in regulation of smooth muscle contraction. Two isoforms, PKGIalpha and PKGIbeta, of the type I protein kinase exist due to alternative splicing of its mRNA.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)A Kinase Anchor Proteins: A structurally-diverse family of intracellular-signaling adaptor proteins that selectively tether specific protein kinase A subtypes to distinct subcellular sites. They play a role in focusing the PROTEIN KINASE A activity toward relevant substrates. Over fifty members of this family exist, most of which bind specifically to regulatory subunits of CYCLIC AMP-DEPENDENT PROTEIN KINASE TYPE II such as CAMP PROTEIN KINASE RIIALPHA or CAMP PROTEIN KINASE RIIBETA.MAP Kinase Kinase 6: A mitogen-activated protein kinase kinase with specificity for P38 MITOGEN-ACTIVATED PROTEIN KINASES.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Focal Adhesion Kinase 1: A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.MAP Kinase Kinase 3: A mitogen-activated protein kinase kinase with specificity for a subset of P38 MITOGEN-ACTIVATED PROTEIN KINASES that includes MITOGEN-ACTIVATED PROTEIN KINASE 12; MITOGEN-ACTIVATED PROTEIN KINASE 13; and MITOGEN-ACTIVATED PROTEIN KINASE 14.Peptide Mapping: Analysis of PEPTIDES that are generated from the digestion or fragmentation of a protein or mixture of PROTEINS, by ELECTROPHORESIS; CHROMATOGRAPHY; or MASS SPECTROMETRY. The resulting peptide fingerprints are analyzed for a variety of purposes including the identification of the proteins in a sample, GENETIC POLYMORPHISMS, patterns of gene expression, and patterns diagnostic for diseases.Butadienes: Four carbon unsaturated hydrocarbons containing two double bonds.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.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Multienzyme Complexes: Systems of enzymes which function sequentially by catalyzing consecutive reactions linked by common metabolic intermediates. They may involve simply a transfer of water molecules or hydrogen atoms and may be associated with large supramolecular structures such as MITOCHONDRIA or RIBOSOMES.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.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.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.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Molecular Weight: The sum of the weight of all the atoms in a molecule.Mitogen-Activated Protein Kinase 14: A 38-kDa mitogen-activated protein kinase that is abundantly expressed in a broad variety of cell types. It is involved in the regulation of cellular stress responses as well as the control of proliferation and survival of many cell types. The kinase activity of the enzyme is inhibited by the pyridinyl-imidazole compound SB 203580.Focal Adhesion Protein-Tyrosine Kinases: A family of non-receptor, PROLINE-rich protein-tyrosine kinases.Mitogen-Activated Protein Kinase 9: A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 48 and 54 KD exist due to multiple ALTERNATIVE SPLICING.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.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.Enzyme Activators: Compounds or factors that act on a specific enzyme to increase its activity.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 enzymesCalcium-Calmodulin-Dependent Protein Kinase Type 1: A monomeric calcium-calmodulin-dependent protein kinase subtype that is expressed in a broad variety of mammalian cell types. Its expression is regulated by the action of CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE. Several isoforms of this enzyme subtype are encoded by distinct genes.PhenanthridinesAminoimidazole Carboxamide: An imidazole derivative which is a metabolite of the antineoplastic agents BIC and DIC. By itself, or as the ribonucleotide, it is used as a condensation agent in the preparation of nucleosides and nucleotides. Compounded with orotic acid, it is used to treat liver diseases.Type C Phospholipases: A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Calcium-Calmodulin-Dependent Protein Kinase Type 4: A monomeric calcium-calmodulin-dependent protein kinase subtype that is primarily expressed in neuronal tissues; T-LYMPHOCYTES and TESTIS. The activity of this enzyme is regulated by its phosphorylation by CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.Cyclic AMP-Dependent Protein Kinase RIalpha Subunit: A type I cAMP-dependent protein kinase regulatory subunit that plays a role in confering CYCLIC AMP activation of protein kinase activity. It has a lower affinity for cAMP than the CYCLIC-AMP-DEPENDENT PROTEIN KINASE RIBETA SUBUNIT.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.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.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.Bucladesine: A cyclic nucleotide derivative that mimics the action of endogenous CYCLIC AMP and is capable of permeating the cell membrane. It has vasodilator properties and is used as a cardiac stimulant. (From Merck Index, 11th ed)Cyclic AMP Response Element-Binding Protein: A protein that has been shown to function as a calcium-regulated transcription factor as well as a substrate for depolarization-activated CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASES. This protein functions to integrate both calcium and cAMP signals.Janus Kinase 2: A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.Phosphothreonine: The phosphoric acid ester of threonine. Used as an identifier in the analysis of peptides, proteins, and enzymes.Mitogen-Activated Protein Kinase 7: A 110-kDa extracellular signal-regulated MAP kinase that is activated in response to cellular stress and by GROWTH FACTOR RECEPTORS-mediated pathways.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.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).Epidermal Growth Factor: A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.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.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.Phosphorylase Kinase: An enzyme that catalyzes the conversion of ATP and PHOSPHORYLASE B to ADP and PHOSPHORYLASE A.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.1-Methyl-3-isobutylxanthine: A potent cyclic nucleotide phosphodiesterase inhibitor; due to this action, the compound increases cyclic AMP and cyclic GMP in tissue and thereby activates CYCLIC NUCLEOTIDE-REGULATED PROTEIN KINASESGene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.Okadaic Acid: A specific inhibitor of phosphoserine/threonine protein phosphatase 1 and 2a. It is also a potent tumor promoter. (Thromb Res 1992;67(4):345-54 & Cancer Res 1993;53(2):239-41)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.Phosphotyrosine: An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.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.Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system.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.Nitriles: Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.Mice, Inbred C57BLSaccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.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.Cyclin-Dependent Kinase 2: A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.MAP Kinase Kinase 7: A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to CYTOKINES.

AMP-activated protein kinase phosphorylation of endothelial NO synthase. (1/2280)

The AMP-activated protein kinase (AMPK) in rat skeletal and cardiac muscle is activated by vigorous exercise and ischaemic stress. Under these conditions AMPK phosphorylates and inhibits acetyl-coenzyme A carboxylase causing increased oxidation of fatty acids. Here we show that AMPK co-immunoprecipitates with cardiac endothelial NO synthase (eNOS) and phosphorylates Ser-1177 in the presence of Ca2+-calmodulin (CaM) to activate eNOS both in vitro and during ischaemia in rat hearts. In the absence of Ca2+-calmodulin, AMPK also phosphorylates eNOS at Thr-495 in the CaM-binding sequence, resulting in inhibition of eNOS activity but Thr-495 phosphorylation is unchanged during ischaemia. Phosphorylation of eNOS by the AMPK in endothelial cells and myocytes provides a further regulatory link between metabolic stress and cardiovascular function.  (+info)

AMP-activated protein kinase: an ultrasensitive system for monitoring cellular energy charge. (2/2280)

The AMP-activated protein kinase cascade is activated by elevation of AMP and depression of ATP when cellular energy charge is compromised, leading to inhibition of anabolic pathways and activation of catabolic pathways. Here we show that the system responds in intact cells in an ultrasensitive manner over a critical range of nucleotide concentrations, in that only a 6-fold increase in activating nucleotide is required in order for the maximal activity of the kinase to progress from 10% to 90%, equivalent to a co-operative system with a Hill coefficient (h) of 2.5. Modelling suggests that this sensitivity arises from two features of the system: (i) AMP acts at multiple steps in the cascade (multistep sensitivity); and (ii) the upstream kinase is initially saturated with the downstream kinase (zero-order ultrasensitivity).  (+info)

AMP-activated kinase reciprocally regulates triacylglycerol synthesis and fatty acid oxidation in liver and muscle: evidence that sn-glycerol-3-phosphate acyltransferase is a novel target. (3/2280)

AMP-activated kinase (AMPK) is activated in response to metabolic stresses that deplete cellular ATP, and in both liver and skeletal muscle, activated AMPK stimulates fatty acid oxidation. To determine whether AMPK might reciprocally regulate glycerolipid synthesis, we studied liver and skeletal-muscle lipid metabolism in the presence of 5-amino-4-imidazolecarboxamide (AICA) riboside, a cell-permeable compound whose phosphorylated metabolite activates AMPK. Adding AICA riboside to cultured rat hepatocytes for 3 h decreased [14C]oleate and [3H]glycerol incorporation into triacylglycerol (TAG) by 50% and 38% respectively, and decreased oleate labelling of diacylglycerol by 60%. In isolated mouse soleus, a highly oxidative muscle, incubation with AICA riboside for 90 min decreased [14C]oleate incorporation into TAG by 37% and increased 14CO2 production by 48%. When insulin was present, [14C]oleate oxidation was 49% lower and [14C]oleate incorporation into TAG was 62% higher than under basal conditions. AICA riboside blocked insulin's antioxidative and lipogenic effects, increasing fatty acid oxidation by 78% and decreasing labelled TAG 43%. Similar results on fatty acid oxidation and acylglycerol synthesis were observed in C2C12 myoblasts, and in differentiated C2C12 myotubes, AICA riboside also inhibited the hydrolysis of intracellular TAG. These data suggest that AICA riboside might inhibit sn-glycerol-3-phosphate acyltransferase (GPAT), which catalyses the committed step in the pathway of glycerolipid biosynthesis. Incubating rat hepatocytes with AICA riboside for both 15 and 30 min decreased mitochondrial GPAT activity 22-34% without affecting microsomal GPAT, diacylglycerol acyltransferase or acyl-CoA synthetase activities. Finally, purified recombinant AMPKalpha1 and AMPKalpha2 inhibited hepatic mitochondrial GPAT in a time-and ATP-dependent manner. These data show that AMPK reciprocally regulates acyl-CoA channelling towards beta-oxidation and away from glycerolipid biosynthesis, and provide strong evidence that AMPK phosphorylates and inhibits mitochondrial GPAT.  (+info)

Apoptosis induced by growth factor withdrawal in fibroblasts overproducing fructose 2,6-bisphosphate. (4/2280)

Fructose 2,6-bisphosphate is a potent endogenous stimulator of glycolysis. A high aerobic glycolytic rate often correlates with increased cell proliferation. To investigate this relationship, we have produced clonal cell lines of Rat-1 fibroblasts that stably express transgenes coding for 6-phosphofructo-2-kinase, which catalyzes the synthesis of fructose 2,6-bisphosphate, or for fructose 2,6-bisphosphatase, which catalyzes its degradation. While serum deprivation in culture reduced the growth rate of control cells, it caused apoptosis in cells overproducing fructose 2,6-bisphosphate. Apoptosis was inhibited by 5-amino-4-imidazolecarboxamide riboside, suggesting that 5'-AMP-activated protein kinase interferes with this phenomenon.  (+info)

Evidence for the involvement of the Glc7-Reg1 phosphatase and the Snf1-Snf4 kinase in the regulation of INO1 transcription in Saccharomyces cerevisiae. (5/2280)

Binding of the TATA-binding protein (TBP) to the promoter is a pivotal step in RNA polymerase II transcription. To identify factors that regulate TBP, we selected for suppressors of a TBP mutant that exhibits promoter-specific defects in activated transcription in vivo and severely reduced affinity for TATA boxes in vitro. Dominant mutations in SNF4 and recessive mutations in REG1, OPI1, and RTF2 were isolated that specifically suppress the inositol auxotrophy of the TBP mutant strains. OPI1 encodes a repressor of INO1 transcription. REG1 and SNF4 encode regulators of the Glc7 phosphatase and Snf1 kinase, respectively, and have well-studied roles in glucose repression. In two-hybrid assays, one SNF4 mutation enhances the interaction between Snf4 and Snf1. Suppression of the TBP mutant by our reg1 and SNF4 mutations appears unrelated to glucose repression, since these mutations do not alleviate repression of SUC2, and glucose levels have little effect on INO1 transcription. Moreover, mutations in TUP1, SSN6, and GLC7, but not HXK2 and MIG1, can cause suppression. Our data suggest that association of TBP with the TATA box may be regulated, directly or indirectly, by a substrate of Snf1. Analysis of INO1 transcription in various mutant strains suggests that this substrate is distinct from Opi1.  (+info)

Phosphorylation control of cardiac acetyl-CoA carboxylase by cAMP-dependent protein kinase and 5'-AMP activated protein kinase. (6/2280)

Acetyl-CoA carboxylase (ACC) is regarded in liver and adipose tissue to be the rate-limiting enzyme for fatty acid biosynthesis; however, in heart tissue it functions as a regulator of fatty acid oxidation. Because the control of fatty acid oxidation is important to the functioning myocardium, the regulation of ACC is a key issue. Two cardiac isoforms of ACC exist, with molecular masses of 265 kDa and 280 kDa (ACC265 and ACC280). In this study, these proteins were purified from rat heart and used in subsequent phosphorylation and immunoprecipitation experiments. Our results demonstrate that 5' AMP-activated protein kinase (AMPK) is able to phosphorylate both ACC265 and ACC280, resulting in an almost complete loss of ACC activity. Although cAMP-dependent protein kinase phosphorylated only ACC280, a dramatic loss of ACC activity was still observed, suggesting that ACC280 contributes most, if not all, of the total heart ACC activity. ACC280 and ACC265 copurified under all experimental conditions, and purification of heart ACC also resulted in the specific copurification of the alpha2 isoform of the catalytic subunit of AMPK. Although both catalytic subunits of AMPK were expressed in crude heart homogenates, our results suggest that alpha2, and not alpha1, is the dominant isoform of AMPK catalytic subunit regulating ACC in the heart. Immunoprecipitation studies demonstrated that specific antibodies for both ACC265 and ACC280 were able to coimmunoprecipitate the alternate isoform along with the alpha2 isoform of AMPK. Taken together, the immunoprecipitation and the purification studies suggest that the two isoforms of ACC in the heart exist in a heterodimeric structure, and that this structure is tightly associated with the alpha2 subunit of AMPK.  (+info)

Effect of AMPK activation on muscle glucose metabolism in conscious rats. (7/2280)

The effect of AMP-activated protein kinase (AMPK) activation on skeletal muscle glucose metabolism was examined in awake rats by infusing them with 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR; 40 mg/kg bolus and 7.5 mg. kg-1. min-1 constant infusion) along with a variable infusion of glucose (49.1 +/- 2.4 micromol. kg-1. min-1) to maintain euglycemia. Activation of AMPK by AICAR caused 2-deoxy-D-[1,2-3H]glucose (2-DG) uptake to increase more than twofold in the soleus and the lateral and medial gastrocnemius compared with saline infusion and occurred without phosphatidylinositol 3-kinase activation. Glucose uptake was also assessed in vitro by use of the epitrochlearis muscle incubated either with AICAR (0.5 mM) or insulin (20 mU/ml) or both in the presence or absence of wortmannin (1.0 microM). AICAR and insulin increased muscle 2-DG uptake rates by approximately 2- and 2.7-fold, respectively, compared with basal rates. Combining AICAR and insulin led to a fully additive effect on muscle glucose transport activity. Wortmannin inhibited insulin-stimulated glucose uptake. However, neither wortmannin nor 8-(p-sulfophenyl)-theophylline (10 microM), an adenosine receptor antagonist, inhibited the AICAR-induced activation of glucose uptake. Electrical stimulation led to an about threefold increase in glucose uptake over basal rates, whereas no additive effect was found when AICAR and contractions were combined. In conclusion, the activation of AMPK by AICAR increases skeletal muscle glucose transport activity both in vivo and in vitro. This cellular pathway may play an important role in exercise-induced increase in glucose transport activity.  (+info)

AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes. (8/2280)

Adenosine 5'-monophosphate-activated protein kinase (AMPK) now appears to be a metabolic master switch, phosphorylating key target proteins that control flux through metabolic pathways of hepatic ketogenesis, cholesterol synthesis, lipogenesis, and triglyceride synthesis, adipocyte lipolysis, and skeletal muscle fatty acid oxidation. Recent evidence also implicates AMPK as being responsible for mediating the stimulation of glucose uptake induced by muscle contraction. In addition, the secretion of insulin by insulin secreting (INS-1) cells in culture is modulated by AMPK activation. The net effect of AMPK activation is stimulation of hepatic fatty acid oxidation and ketogenesis, inhibition of cholesterol synthesis, lipogenesis, and triglyceride synthesis, inhibition of adipocyte lipolysis and lipogenesis, stimulation of skeletal muscle fatty acid oxidation and muscle glucose uptake, and modulation of insulin secretion by pancreatic beta-cells. In skeletal muscle, AMPK is activated by contraction. Type 2 diabetes mellitus is likely to be a disease of numerous etiologies. However, defects or disuse (due to a sedentary lifestyle) of the AMPK signaling system would be predicted to result in many of the metabolic perturbations observed in Type 2 diabetes mellitus. Increased recruitment of the AMPK signaling system, either by exercise or pharmaceutical activators, may be effective in correcting insulin resistance in patients with forms of impaired glucose tolerance and Type 2 diabetes resulting from defects in the insulin signaling cascade.  (+info)

*Protein kinase, AMP-activated, alpha 1

"Stimulation of glucose transport by AMP-activated protein kinase via activation of p38 mitogen-activated protein kinase". J. ... 1996). "Characterization of the AMP-activated protein kinase kinase from rat liver and identification of threonine 172 as the ... Bolster DR, Crozier SJ, Kimball SR, Jefferson LS (2002). "AMP-activated protein kinase suppresses protein synthesis in rat ... AMP-activated protein kinase catalytic subunit alpha-1 is an enzyme that in humans is encoded by the PRKAA1 gene. The protein ...

*PRKAB2

5'-AMP-activated protein kinase subunit beta-2 is an enzyme that in humans is encoded by the PRKAB2 gene. The protein encoded ... 2000). "Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding". Biochem. J. 346 ... "Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding". Biochem. J. ENGLAND. ... "Entrez Gene: PRKAB2 protein kinase, AMP-activated, beta 2 non-catalytic subunit". Cheung, P C; Salt I P; Davies S P; Hardie D G ...

*AMP-activated protein kinase

"AMP-activated protein kinase kinase activity and phosphorylation of AMP-activated protein kinase in contracting muscle of ... 5' AMP-activated protein kinase or AMPK or 5' adenosine monophosphate-activated protein kinase is an enzyme (EC 2.7.11.31) that ... It should not be confused with cyclic AMP-activated protein kinase (protein kinase A). AMPK is a heterotrimeric protein complex ... "Endurance training increases LKB1 and MO25 protein but not AMP-activated protein kinase kinase activity in skeletal muscle". Am ...

*Metformin

"Metformin and phenformin activate AMP-activated protein kinase in the heart by increasing cytosolic AMP concentration". Am J ... 2002). "Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes". ... Towler MC; Hardie DG (2007). "AMP-activated protein kinase in metabolic control and insulin signaling". Circ Res. 100 (3): 328- ... 2008). "Metformin inhibits hepatic gluconeogenesis through AMP-activated protein kinase-dependent regulation of the orphan ...

*Aspirin

In 2012, salicylic acid was found to activate AMP-activated protein kinase, which has been suggested as a possible explanation ... "The ancient drug salicylate directly activates AMP-activated protein kinase". Science. 336 (6083): 918-922. Bibcode:2012Sci... ... Acetylation of cellular proteins is a well-established phenomenon in the regulation of protein function at the post- ... About 50-80% of salicylate in the blood is bound to albumin protein, while the rest remains in the active, ionized state; ...

*MTORC1

Nagalingam A, Arbiser JL, Bonner MY, Saxena NK, Sharma D (2012). "Honokiol activates AMP-activated protein kinase in breast ... Wang S, Song P, Zou MH (Jun 2012). "AMP-activated protein kinase, stress responses and cardiovascular diseases". Clinical ... Hardie DG (Oct 2007). "AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy". Nature Reviews Molecular ... which activates the Ras G protein. Ras activates Raf (MAPKKK), which activates Mek (MAPKK), which activates Erk (MAPK). Erk can ...

*PRKAG3

5'-AMP-activated protein kinase subunit gamma-3 is an enzyme that in humans is encoded by the PRKAG3 gene. The protein encoded ... "Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding". Biochem. J. 346 Pt 3 (3 ... activated protein kinase alpha2beta2gamma3 complexes by AMP and implications of the mutations in the gamma3-subunit for the AMP ... "Entrez Gene: PRKAG3 protein kinase, AMP-activated, gamma 3 non-catalytic subunit". Woods A, Cheung PC, Smith FC, Davison MD, ...

*PRKAG2

AMP-activated protein kinase subunit gamma-2 is an enzyme that in humans is encoded by the PRKAG2 gene. AMP-activated protein ... 2001). "An activating mutation in the gamma1 subunit of the AMP-activated protein kinase". FEBS Lett. 500 (3): 163-8. doi: ... 2000). "Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding". Biochem. J. 346 ... "Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding". Biochem. J. ENGLAND. ...

*Acadesine

A specific method for activating AMP-activated protein kinase in intact cells?". Eur. J. Biochem. 229 (2): 558-65. doi:10.1111/ ... Kim JE, Kim YW, Lee IK, Kim JY, Kang YJ, Park SY (March 2008). "AMP-activated protein kinase activation by 5-aminoimidazole-4- ... Lemieux K, Konrad D, Klip A, Marette A (September 2003). "The AMP-activated protein kinase activator AICAR does not induce ... Acadesine acts as an AMP-activated protein kinase agonist. It stimulates glucose uptake and increases the activity of p38 ...

*Louise McCullough

"Pharmacological inhibition of AMP-activated protein kinase provides neuroprotection in stroke". J. Biol. Chem. 280 (21): 20493- ...

*Carotid body

AMP-activated protein kinase (AMPK) has also been proposed in hypoxia sensing. This enzyme is activated during times of net ... "AMP-ACTIVATED PROTEIN KINASE MEDIATES CAROTID BODY EXCITATION BY HYPOXIA". J Biol Chem. 282 (11): 8092-8. doi:10.1074/jbc. ... In normoxia, haem-oxygenase generates carbon monoxide (CO), CO activates the large conductance calcium-activated potassium ... AMPK has a number of targets and it appears that, in the carotid body, when AMPK is activated by hypoxia, it leads to ...

*Stress granule

Mahboubi H, Barisé R, Stochaj U (July 2015). "5'-AMP-activated protein kinase alpha regulates stress granule biogenesis". ... these include the master energy sensor AMP-activated protein kinase (AMPK), the O-GlcNAc transferase enzyme (OGT), and the pro- ... Reineke LC, Lloyd RE (March 2015). "The stress granule protein G3BP1 recruits protein kinase R to promote multiple innate ... the APEX enzyme will be briefly activated to biotinylate all proteins in close proximity to the protein of interest, in this ...

*AICA ribonucleotide

A specific method for activating AMP-activated protein kinase in intact cells? Eur J Biochem 229:558-565(1995) Galinanes M, ... AICAR is an analog of adenosine monophosphate (AMP) that is capable of stimulating AMP-dependent protein kinase (AMPK) activity ... Potential Role of AMP-Activated Protein Kinase. Pharmacology Toxicology 10-16 (2009).doi:10.1111/j.1742-7843.2009.00402.x Zhang ... AMP-activated protein kinase mediates preconditioning in cardiomyocytes by regulating activity and trafficking of sarcolemmal ...

*HMG-CoA reductase

... a great deal of research on the identity of upstream kinases that phosphorylate and activate the AMP-activated protein kinase. ... but a decrease in activity of the enzyme is caused by an AMP-activated protein kinase, which responds to an increase in AMP ... Hardie DG, Scott JW, Pan DA, Hudson ER (Jul 2003). "Management of cellular energy by the AMP-activated protein kinase system". ... identification of the site phosphorylated by the AMP-activated protein kinase in vitro and in intact rat liver". The EMBO ...

*CBS domain

"Structural basis for AMP binding to mammalian AMP-activated protein kinase". Nature. 449 (7161): 496-500. doi:10.1038/ ... Townley R, Shapiro L (March 2007). "Crystal structures of the adenylate sensor from fission yeast AMP-activated protein kinase ... voltage gated chloride channels and AMP-activated protein kinase (AMPK). CBS domains regulate the activity of associated ... These standalone CBS domain proteins might form complexes upon binding to other proteins such as kinases to which they interact ...

*List of drugs banned by WADA

PPARδ-AMP-activated protein kinase (AMPK) axis agonists (e.g. AICAR) are also banned. Stimulants directly affect the central ... Also banned are any other growth factor affecting muscle, tendon or ligament protein synthesis/degradation, vascularization, ... Metabolic modulators including peroxisome proliferator-activated receptor delta (PPARδ) agonists (e.g., GW 1516), ... and proteins, and regulate glycogen and blood pressure levels.They possess pronounced anti-inflammatory activity and cause ...

*Randle cycle

This leads to an activation of AMP-activated protein kinase (AMPK) as the AMP concentration rises in intracellular fluids and ... Clark H, Carling D, Saggerson D (2004). "Covalent activation of heart AMP-activated protein kinase in response to physiological ... AMP-activated protein kinase (AMPK) is reported to phosphorylate and inactivate liver ACC. This in turn decreases malonyl-CoA ... "Glucose Autoregulates Its Uptake in Skeletal Muscle-Involvement of AMP-Activated Protein Kinase". Diabetes. 52: 1635-1640. doi: ...

*Histone deacetylase 5

AMP-activated protein kinase regulation of the glucose transporter GLUT4 occurs by phosphorylation of HDAC5. HDAC5 is involved ... "AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5". Diabetes. 57 (4): 860-867 ... Vega RB, Harrison BC, Meadows E, Roberts CR, Papst PJ, Olson EN, McKinsey TA (2004). "Protein kinases C and D mediate agonist- ... "Activation of the myocyte enhancer factor-2 transcription factor by calcium/calmodulin-dependent protein kinase-stimulated ...

*ACACB

AMP-activated protein kinase activity and protein expression are regulated by endurance training in human skeletal muscle". ... Kahn BB, Alquier T, Carling D, Hardie DG (January 2005). "AMP-activated protein kinase: ancient energy gauge provides clues to ... Ruderman N, Prentki M (April 2004). "AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome". Nature Reviews ... Protein Expression and Purification. 51 (1): 11-21. doi:10.1016/j.pep.2006.06.005. PMID 16854592. Diaz FJ, Meary A, Arranz MJ, ...

*PRKAA2

... protein kinase, AMP-activated, alpha 2 catalytic subunit". Hardie DG, MacKintosh RW (1995). "AMP-activated protein ... The protein encoded by this gene is a catalytic subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer ... "Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase". Nature. 415 (6869): 339-43. doi:10.1038/ ... 5'-AMP-activated protein kinase catalytic subunit alpha-2 is an enzyme that in humans is encoded by the PRKAA2 gene. ...

*Hypoxia in fish

doi:10.1016/S1546-5098(08)00008-3. Jibb, LA; Richards, JG (2008). "AMP-activated protein kinase activity during metabolic rate ... Decreases in the expression of genes involved in protein synthesis, such as elongation factor-2 and several ribosomal proteins ... A decrease in protein synthesis is an important response to hypoxia in order to decrease ATP demand for whole organism ... In addition to a reduction in the rate of protein synthesis, it appears that some species of hypoxia-tolerant fish conserve ...

*Lipogenesis

This rise activates AMP-activated protein kinase, which phosphorylates ACC and thereby inhibits fat synthesis. This is a useful ... "MAP kinases Erk1/2 phosphorylate sterol regulatory element-binding protein (SREBP)-1a at serine 117 in vitro". The Journal of ... AMP and ATP concentrations of the cell act as a measure of the ATP needs of a cell. When ATP is depleted, there is a rise in ... ACC is also activated by citrate. When there is abundant acetyl-CoA in the cell cytoplasm for fat synthesis, it proceeds at an ...

*Cyclic adenosine monophosphate

It should not be confused with 5'-AMP-activated protein kinase (AMP-activated protein kinase). Earl Sutherland of Vanderbilt ... In eukaryotes, cyclic AMP works by activating protein kinase A (PKA, or cAMP-dependent protein kinase). PKA is normally ... Not all protein kinases respond to cAMP. Several classes of protein kinases, including protein kinase C, are not cAMP-dependent ... or may become activated or inhibited enzymes. Protein kinase A can also phosphorylate specific proteins that bind to promoter ...

*ACACA

"Kidney bean husk extracts exert antitumor effect by inducing apoptosis involving AMP-activated protein kinase signaling pathway ... "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): ... "Specific pattern of LKB1 and phospho-acetyl-CoA carboxylase protein immunostaining in human normal tissues and lung carcinomas ... "Identification and characterization of proteins interacting with SIRT1 and SIRT3: implications in the anti-aging and metabolic ...

*GLUT4

Mu J, Brozinick JT, Valladares O, Bucan M, Birnbaum MJ (May 2001). "A role for AMP-activated protein kinase in contraction- and ... and this is likely regulated by RAC1 and AMP-activated protein kinase. Muscle stretching also stimulates GLUT4 translocation ... PIP3 is specifically recognized by PKB (protein kinase B) and by PDK1, which can phosphorylate and activate PKB. Once ... allowing for Rab protein to change from its GDP to GTP bound state. Inhibition of the GTPase-activating domain leaves proteins ...

*Olfactory receptor neuron

The activated OR in turn activates the intracellular G-protein, GOLF (GNAL), adenylate cyclase and production of cyclic AMP ( ... "Phosphorylation and inhibition of olfactory adenylyl cyclase by CaM kinase II in Neurons: a mechanism for attenuation of ... CaMKII will be activated by the presence of CaM, which will phosphorylate ACIII and reduce cAMP production. CaMKII will also ... The surface of these cilia is covered with olfactory receptors, a type of G protein-coupled receptor. Each olfactory receptor ...
It has previously been reported that exercise causes an increase in glucose uptake in skeletal muscle and also an increase in 5 AMP-activated protein kinase (AMPK) activity. 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICA-riboside), an analog of adenosine, is taken up into cells and phosphorylated to form AICA-riboside monophosphate (ZMP), which can also activate AMPK. This study was designed to determine whether the increase in glucose uptake observed with AMPK activation by AICA-riboside is due to GLUT4 translocation from an intracellular location to the plasma membranes, similar to that seen in response to contraction. Rat hindlimbs were perfused with Krebs-Henseleit bicarbonate containing 4% bovine serum albumin, washed bovine erythrocytes, 8 mmol/l glucose, and +/-2 mmol/AICA-riboside or +/-60 nmol/l insulin. Perfusion medium containing AICA-riboside was found to significantly increase AMPK activity, glucose uptake, and GLUT4 translocation in skeletal muscle above basal ...
Cancer Chemother Pharmacol. 2014 Jul;74(1):167-76. doi: 10.1007/s00280-014-2451-7. Epub 2014 May 20. Research Support, Non-U.S. Govt
The 5′ adenosine monophosphate-activated protein kinase (AMPK) is a heterotrimeric, evolutionary conserved enzyme which has emerged as a critical regulator of skeletal muscle cellular bioenergetics. AMPK is activated by both chemical (adipokines) and mechanical (stretch, contraction) stimuli leading to metabolic changes within muscle cells that include increased fatty acid oxidation, glucose uptake and glycolysis, as well as the stimulation and regulation of mitochondrial biogenesis. Collectively these acute responses and chronic adaptations act to reduce cellular disturbances, resulting in tighter metabolic control and maintenance of energy homeostasis. This brief review will describe the structure, function and activation of AMPK in skeletal muscle and how this ubiquitous molecule may be a plausible target for the treatment of several lifestyle-related metabolic disorders.
Introduction: We have reported that serum Interleukin-18 (IL-18) concentrations increased according to worsening heart failure (HF) functional class. However, the pathological roles of serum IL-18 elevation in HF have not been fully elucidated. The purpose of this study was to elucidate the role of IL-18 in adaptation to pressure overload in IL-18 null mice.. Hypothesis: We hypothesized that IL-18 plays a key role in pressure overload-induced hypertrophic responses by enhancing mitochondrial function.. Methods: Ten-week-old male C57BL6/J-background wild type (WT) mice and C57BL6/J-background IL-18 null (IL-18-/-) were subjected to transaortic constriction (TAC). Cardiac function was assessed by transthoracic echocardiography every week. Two weeks after TAC, myocardial samples were obtained. Detection of cardiac gene expressions by q-RT PCR and quantification of phospho-proteins by western blot were performed. An AMPK activator (AICAR 100mg/kg,) was given intraperitoneally everyday after TAC ...
Journal of Diabetes Research is a peer-reviewed, Open Access journal that publishes research articles, review articles, and clinical studies related to type 1 and type 2 diabetes. The journal welcomes submissions focusing on the epidemiology, etiology, pathogenesis, management, and prevention of diabetes, as well as associated complications, such as diabetic retinopathy, neuropathy and nephropathy.
Mammalian AMP-activated protein kinase presents strong structural and functional similarities with the yeast sucrose non-fermenting 1 (Snf1) kinase involved in the derepression of glucose-repressed genes. It is now clearly established that AMP-activated protein kinase in the liver decreases glycolytic/lipogenic gene expression as well as genes involved in hepatic glucose production. This is achieved through a decreased transcriptional efficiency of transcription factors such as sterol-regulatory-element-binding protein-1c, carbohydrate-response-element-binding protein, hepatocyte nuclear factor 4α or forkhead-related protein. Clearly, the long-term consequences of AMP-activated protein kinase activation have to be taken into account if activators of this enzyme are to be designed as anti-diabetic drugs.. ...
Oncogenic transcription factor Myc deregulates the cell cycle and simultaneously reprograms cellular metabolism to meet the biosynthetic and bioenergetic needs of proliferation. Myc also sensitizes cells to mitochondria-dependent apoptosis. Although metabolic reprogramming has been circumstantially connected to vulnerability to apoptosis, the connecting molecular pathways have remained poorly defined. Our recent studies revealed that Myc-dependent ATP depletion activates the energy sensor AMP-activated protein kinase (AMPK), which induces stabilizing phosphorylation of p53 at Ser15. AMPK-stabilized tumor suppressor protein p53 then accumulates in the mitochondria and interacts with the protein complex comprised of Bak and Bcl-xL, to sensitize cells to apoptosis. These results reveal an unexpected pro-apoptotic function of AMPK in context of Myc transformed cells.. We have explored possibilities to therapeutically exploit the Myc-AMPK facilitated apoptosis pathway. We show that a BH3-mimetic ...
Hypoxic pulmonary vasoconstriction is a vital homeostatic mechanism that aids ventilation-perfusion matching in the lung, for which the underlying mechanism(s) remains controversial. However, our most recent investigations strongly suggest that hypoxic pulmonary vasoconstriction is precipitated, at least in part, by the inhibition of mitochondrial oxidative phosphorylation by hypoxia, an increase in the AMP/ATP ratio and consequent activation of AMP-activated protein kinase (AMPK). Unfortunately, these studies lacked the definitive proof that can only be provided by selectively blocking AMPK-dependent signalling cascades. The aim of the present study was, therefore, to determine the effects of the AMPK inhibitor compound C upon: (1) phosphorylation in response to hypoxia of a classical AMPK substrate, acetyl CoA carboxylase, in rat pulmonary arterial smooth muscle and (2) hypoxic pulmonary vasoconstriction in rat isolated intrapulmonary arteries. Acetyl CoA carboxylase phosphorylation was increased
Pancreatic islets of Langerhans play an essential role in controlling whole body glucose metabolism by releasing key regulating hormones, such as insulin and glucagon. Defective insulin or glucagon secretion has been implicated in several metabolic diseases, such as obesity and diabetes. Therefore, intrinsically well-regulated insulin and glucagon release from the islets is key to maintaining glucose homeostasis. AMP-activated protein kinase (AMPK), an ancient energy (AMP/ATP) sensor and its principal upstream kinase, STK11 (liver kinase B1, LKB1), a tumour suppressor, have been found to regulate glucose metabolism in several peripheral tissues such as the liver, muscle, hypothalamus, and adipose tissue, and are found to be expressed in both pancreatic β and α cells. However, the role of AMPK and LKB1 in pancreatic islets in controlling hormone secretion and thus the whole body glucose metabolism has never been investigated in vivo. In this study, I sought to understand how AMPK and LKB1 ...
The AMP-activated protein kinase (AMPK) is a metabolic stress-sensing αβγ heterotrimer responsible for energy homeostasis. Pharmacological inhibition of AMPK is regarded as a therapeutic strategy in some disease settings including obesity and cancer; however, the broadly used direct AMPK inhibitor compound C suffers from poor selectivity. We have discovered a dihydroxyquinoline drug (MT47-100) with novel AMPK regulatory properties, being simultaneously a direct activator and inhibitor of AMPK complexes containing the β1 or β2 isoform, respectively. Allosteric inhibition by MT47-100 was dependent on the β2 carbohydrate-binding module (CBM) and determined by three non-conserved CBM residues (Ile81, Phe91, Ile92), but was independent of β2-Ser108 phosphorylation. Whereas MT47-100 regulation of total cellular AMPK activity was determined by β1/β2 expression ratio, MT47-100 augmented glucose-stimulated insulin secretion from isolated mouse pancreatic islets via a β2-dependent mechanism. Our
TY - JOUR. T1 - AMP-activated protein kinase and hypoxic pulmonary vasoconstriction. AU - Robertson,Tom P.. AU - Mustard,Kirsteen J. W.. AU - Lewis,Tristan H.. AU - Clark,Jill H.. AU - Wyatt,Christopher N.. AU - Blanco,Elisa A.. AU - Peers,Chris. AU - Hardie,D. Grahame. AU - Evans,A. Mark. PY - 2008/10/24. Y1 - 2008/10/24. N2 - Hypoxic pulmonary vasoconstriction is a vital homeostatic mechanism that aids ventilation-perfusion matching in the lung, for which the underlying mechanism(s) remains controversial. However, our most recent investigations strongly suggest that hypoxic pulmonary vasoconstriction is precipitated, at least in part, by the inhibition of mitochondrial oxidative phosphorylation by hypoxia, an increase in the AMP/ATP ratio and consequent activation of AMP-activated protein kinase (AMPK). Unfortunately, these studies lacked the definitive proof that can only be provided by selectively blocking AMPK-dependent signalling cascades. The aim of the present study was. therefore, to ...
Abstract. Vincristine is extensively used chemotherapeutic medicine to treat leukemia. However, it remains a critical clinical problem with regard to its toxicity and drug-resistance. AMP-activated protein kinase (AMPK) is an energy sensor that is pivotal in maintaining cell metabolic homeostasis. It is reported that AMPK is involved in vincristine-induced apoptosis. However, whether AMPK is involved in chemotherapy-resistance is largely unclear. It is well-documented that metformin, a widely used medicine to treat type II diabetes, possesses anti-cancer activities, yet whether metformin affects leukemia cell viability via vincristine is unknown. In this study, we showed that both AMPKα1 mRNA and phosphorylated AMPK protein levels were significantly decreased in clinical leukemia samples. We further demonstrated that metformin sensitized leukemia cells to vincristine-induced apoptosis in an AMPK-dependent manner. In addition, knockdown of AMPKα1 significantly reduced the effects of metformin ...
D942 compound: a furancarboxylic acid derivative, which increases glucose uptake in L6 myocytes through AMP-activated protein kinase (AMPK) activation
The exact function(s) of the GBD remains unclear, although there are several experimental findings linking AMPK with glycogen; however, these observations are currently difficult to synthesize into a single, all-encompassing hypothesis. The GBD does cause a partial localization of AMPK to glycogen particles, where one of its known downstream targets - glycogen synthase - resides (Hudson et al., 2003). There is also indirect evidence that glycogen regulates AMPK activity: in both rat (Wojtaszewski et al., 2002) and human (Wojtaszewski et al., 2003) skeletal muscle, a high content of glycogen represses activation of AMPK. This makes physiological sense because if muscle glycogen content is high it tends to be used preferentially as fuel and, although AMPK activation stimulates the usage by muscle of alternative fuels such as blood glucose and fatty acids, it is not required for glycogen breakdown or glycolysis. As yet, repression of AMPK activation by glycogen has not been reproduced in a ...
Background & Aims: Aspirin reduces the incidence of and mortality from colorectal cancer (CRC) by unknown mechanisms. Cancer cells have defects in signaling via the mechanistic target of rapamycin (mTOR), which regulates proliferation. We investigated whether aspirin affects adenosine monophosphate-activated protein kinase (AMPK) and mTOR signaling in CRC cells. Methods: The effects of aspirin on mTOR signaling, the ribosomal protein S6, S6 kinase 1 (S6K1), and eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) were examined in CRC cells by immunoblotting. Phosphorylation of AMPK was measured; the effects of loss of AMPKa on the aspirin-induced effects of mTOR were determined using small interfering RNA (siRNA) in CRC cells and in AMPK mouse embryonic fibroblasts. LC3 and ULK1 were used as markers of autophagy. We analyzed rectal mucosa samples from patients given 600 mg aspirin, once daily for 1 week. Results: Aspirin reduced mTOR signaling in CRC cells by inhibiting the ...
Exercise-induced glucose uptake in skeletal muscle is mediated by an insulin-independent mechanism, but the actual signals to glucose transport in response to muscle contraction have not been identified. The 5´-AMP-activated protein kinase (AMPK) has emerged as a putative mediator of contraction-induced glucose transport, although no conclusive evidence has been provided so far. Recent experiments in AMPK transgenic mice suggest that glucose transport induced by 5-amino-4-imidazolecarboxamide riboside (AICAR) or hypoxia is mediated by AMPK. In contrast, contraction-induced glucose transport in rodent skeletal muscle induced by electrical stimulation in vitro or in situ is not influenced or is only partially reduced by abolishing both or one of the catalytic AMPK subunits. This is compatible with exercise studies done in humans, where no tight correlation is found between AMPK activity and glucose uptake during exercise. Taken together, these results question an essential role of AMPK in ...
AMP-activated protein kinase (AMPK) is an evolutionally conserved protein kinase that serves as an energy guardian to help cells adapt to various metabolic stress including hypoxia. Because the role of AMPK in cancers has not been fully elucidated, in this study we investigated the expression and activation of AMPK in lung adenocarcinoma (LADC) cells and tissue ...
AMP-activated protein kinase (AMPK) is an enzyme that senses and regulates cellular energy balance thus playing a key role in homeostasis. As such it is a target for treatment of metabolic disorders such as type II diabetes. AMPK is a hetero-trimeric complex composed of an α, β and γ subunit. α contains the catalytic kinase domain, β is a scaffolding subunit that enables complex formation and γ monitors cellular energy via nucleotide binding to its CBS domains. AMPK is primarily activated by phosphorylation at Thr-172 on the activation loop in the kinase domain. It exerts its cellular effects via phosphorylation of a range of downstream targets involved in different aspects of energy production & utilization. The aim of this thesis is to characterize the mechanistic basis of energy regulation of mammalian AMPK via structural and binding measurements. Fluorescence studies have been facilitated by the use of N-methylanthraniloyl (mant) labelled AMP and of β-Nicotinamide adenine dinucleotide ...
Integrins are cell surface receptors that physically bridge the extracellular matrix to the cytoskeleton and responsible for adhesion, migration, and signaling. Integrin function is intimately controlled by their membrane traffic. For example, integrins are dynamically internalized from the cell posterior and recycled to the cell anterior during cell migration. Misregulation of integrins is intimately linked with cancer progression, including metastasis and cell proliferation and survival. We have recently uncovered that integrin membrane traffic is controlled by AMP-activated protein kinase (AMPK), an energy stress sensing kinase within cells at becomes activated upon energy stress such as by an increase in cell AMP:ATP ratio. I confirmed that AMPK activation resulted in a reduction of cell surface β1-integrin. Using assays that selectively measure integrin exocytosis and endocytosis, I found that AMPK activation regulates β1-integrin recycling and possibly endocytosis. I demonstrated that ...
Identification of phosphorylation sites in AMP-activated protein kinase (AMPK) for upstream AMPK kinases and study of their roles by site-directed ...
AMPK (5′-AMP-activated protein kinase) is emerging as a metabolic master switch, by which cells in both mammals and lower organisms sense and decode changes in energy status. Changes in AMPK activity have been shown to regulate glucose transport in muscle and glucose production by the liver. Moreover, AMPK appears to be a key regulator of at least one transcription factor linked to a monogenic form of diabetes mellitus. As a result, considerable efforts are now under way to explore the usefulness of AMPK as a therapeutic target for other forms of this disease. Here we review this topic, and discuss new findings which suggest that AMPK may play roles in regulating insulin release and the survival of pancreatic islet β-cells, and nutrient sensing by the brain.. ...
Objective- Vascular endothelial cells (ECs) confer atheroprotection at locations of the arterial tree where pulsatile laminar flow (PS) exists with a high shear stress and a large net forward direction. We investigated whether the PS-induced expression of the transcription factor Krüppel-Like Factor 2 (KLF2) in cultured ECs and its expression in the mouse aorta is regulated by AMP-activated protein kinase (AMPK).. Methods and Results- AMPK inhibition by Compound C or siRNA had a significant blocking effect on the PS-induced KLF2 expression. The induction of KLF2 by PS led to the increase in eNOS and the suppression of ET-1, which could be reversed by KLF2 siRNA. In addition, PS induced the phosphorylation of ERK5 and MEF2 which are necessary for the KLF2 expression. These mechanotransduction events were abrogated by the blockade of AMPK. Furthermore, the phosphorylation levels of ERK5 and MEF2, as well as the expression of KLF2, were significantly reduced in the aorta of AMPKα2 knockout mice ...
AMP-activated protein kinase (AMPK) is a key regulator of cellular and body energy homeostasis. We previously demonstrated that AMPK activation in osteoblasts increases in vitro bone formation while deletion of the Ampkα1 (Prkaa1) subunit, the dominant catalytic subunit expressed in bone, leads to decreased bone mass in vivo. To investigate the cause of low bone mass in the Ampkα1(-/-) mice, we analysed bone formation and resorption in the tibia of these mice by dynamic histomorphometry and determined whether bone turnover can be stimulated in the absence of the Ampkα1 subunit. We subjected 12-week-old Ampkα1(+)(/)(+) and Ampkα1(-/-) mice to ovariectomy (OVX), intermittent PTH (iPTH) administration (80 μg/kg per day, 5 days/week) or both OVX and iPTH hormonal challenges. Tibiae were harvested from these mice and bone micro-architecture was determined by micro-computed tomography. We show for the first time that Ampkα1(-/-) mice have a high bone turnover at the basal level in favour of ...
Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Beta non-catalytic subunit acts as a scaffold on which the AMPK complex assembles, via its C-terminus that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1, PRKAG2 or PRKAG3) (By similarity).
In the adult brain, programmed death of neural stem cells is considered to be critical for tissue homeostasis and cognitive function and is dysregulated in neurodegeneration. Previously, we have reported that adult rat hippocampal neural (HCN) stem cells undergo autophagic cell death (ACD) following insulin withdrawal. Because the apoptotic capability of the HCN cells was intact, our findings suggested activation of unique molecular mechanisms linking insulin withdrawal to ACD rather than apoptosis. Here, we report that phosphorylation of autophagy-associated protein p62 by AMP-activated protein kinase (AMPK) drives ACD and mitophagy in HCN cells. Pharmacological inhibition of AMPK or genetic ablation of the AMPK alpha 2 subunit by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 genome editing suppressed ACD, whereas AMPK activation promoted ACD in insulin-deprived HCN cells. We found that following insulin withdrawal AMPK phosphorylated p62 at a novel site, ...
Neuronal polarization lies at the heart of neuronal development, synaptic wiring, and interneuronal communication. Although much progress has been made in understanding axon growth and path finding, the mechanisms that regulate axonal neurite selection and polarity initiation remain poorly understood. Rapid axon growth requires a large quantity of building material and efficient intracellular transport. Coordination between axon initiation and cellular energy homeostasis may thus be important during the early stages of neuronal polarization. Using cultured hippocampal neurons and embryonic brain slices, Amato et al. investigated the role of adenosine monophosphate-activated protein kinase (AMPK), which is involved in the sensing and regulation of bioenergy homeostasis, in neuronal polarization. Up-regulation of AMPK activity reduced the proportion of neurons possessing a typical axon. The ability of AMPK to inhibit polarization was restricted to the early stages of polarization; AMPK activation ...
AMP-activated protein kinase (AMPK) is a major regulator of skeletal muscle metabolism with relevance to agriculture and human health. During the conversion of muscle to meat, the rate and extent of postmortem metabolism and pH decline largely determine pork quality development. Pigs with the AMPKγ3 R200Q mutation generate pork with low ultimate pH (pHu); this is attributed to high glycogen content, and greater â potentialâ to produce lactate and H+. We hypothesized that decreasing muscle phosphocreatine and creatine would decrease ATP buffering capacity, resulting in earlier termination of glycolysis and pH decline. Dietary supplementation with the creatine analogue, β-GPA, decreased muscle total creatine but negatively affected performance. Another experiment was conducted using control or β-GPA diet and wild type and AMPKγ3R200Q pigs in a 2à 2 factorial design. The loss of muscle total creatine was important in maintenance of ATP levels in AMPKγ3R200Q muscle early ...
Heterotrimeric AMP-activated protein kinase (AMPK) is crucial for energy homeostasis of eukaryotic cells and organisms. Here we report on (i) bacterial expression of untagged mammalian AMPK isoform combinations, all containing gamma(1), (ii) an automated four-dimensional purification protocol, and (iii) biophysical characterization of AMPK heterotrimers by small angle x-ray scattering in solution (SAXS), transmission and scanning transmission electron microscopy (TEM, STEM), and mass spectrometry (MS). AMPK in solution at low concentrations (~1 mg/ml) largely consisted of individual heterotrimers in TEM analysis, revealed a precise 1:1:1 stoichiometry of the three subunits in MS, and behaved as an ideal solution in SAXS. At higher AMPK concentrations, SAXS revealed concentration-dependent, reversible dimerization of AMPK heterotrimers and formation of higher oligomers, also confirmed by STEM mass measurements. Single particle reconstruction and averaging by SAXS and TEM, respectively, revealed similar
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The hypothalamic AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) pathway is known to play an important role in the control of food intake and energy expenditure. Here, we hypothesize that citrate, an intermediate metabolite, activates hypothalamic ACC and is involved in the control of energy mobilization. Initially, we showed that ICV citrate injection decreased food intake and diminished weight gain significantly when compared to control and pair-fed group results. In addition, we showed that intracerebroventricular (ICV) injection of citrate diminished (80% of control) the phosphorylation of ACC, an important AMPK substrate. Furthermore, citrate treatment inhibited (75% of control) hypothalamic AMPK phosphorylation during fasting. In addition to its central effect, ICV citrate injection led to low blood glucose levels during glucose tolerance test (GTT) and high glucose uptake during hyperglycemic-euglycemic clamp. Accordingly, liver glycogen content was higher in animals ...
Connexios Life Sciences and Boehringer Ingelheim are collaborating on the development of AMP-activated protein kinase (AMPK) stimulants for the treatment of
Author: Bitrián Satorra, M.; Genre: Thesis; Published online: 2011; Title: Regulation of plant stress responses by AMP-activated protein kinases
5-AMP-activated protein kinase (AMPK) has been suggested to be a metabolic master switch regulating various aspects of muscle glucose and fat metabolism. In isolated rat skeletal muscle, glucose suppresses the activity of AMPK and in human muscle glycogen loading decreases exercise-induced AMPK activation. We hypothesized that oral glucose ingestion during exercise would attenuate muscle AMPK activation. Nine male subjects performed two bouts of one-legged knee-extensor exercise at 60% of maximal workload. The subjects were randomly assigned to either consume a glucose containing drink or a placebo drink during the two trials. Muscle biopsies were taken from the vastus lateralis before and after 2 h of exercise. Plasma glucose was higher (6.0 +/- 0.2 vs. 4.9 +/- 0.1 mmol L-1, P , 0.001), whereas glycerol (44.8 +/- 7.8 vs. 165.7 +/- 22.3 micromol L-1), and free fatty acid (169.3 +/- 9.5 vs. 1161 +/- 144.9 micromol L-1) concentrations were lower during the glucose compared to the placebo trial ...
AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already ...
Hypoxic inhibition of K+ channels in type I cells is believed to be of central importance in carotid body chemotransduction. We have recently suggested that hypoxic channel inhibition is mediated by AMP-activated protein kinase (AMPK). Here, we have further explored the modulation by AMPK of recombinant K+ channels (expressed in HEK293 cells) whose native counterparts are considered O2-sensitive in the rat carotid body. Inhibition of maxiK channels by AMPK activation with AICAR was found to be independent of [Ca2+]i and occurred regardless of whether the α subunit was co-expressed with an auxiliary β subunit. All effects of AICAR were fully reversed by the AMPK inhibitor compound C. MaxiK channels were also inhibited by the novel AMPK activator A-769662 and by intracellular dialysis with the constitutively active, truncated AMPK mutant, T172D. The molecular identity of the O2-sensitive leak K+ conductance in rat type I cells remains unclear, but shares similarities with TASK-1 and TASK-3. Recombinant
5-AMP-activated protein kinase catalytic subunit alpha-1 is an enzyme that in humans is encoded by the PRKAA1 gene. The protein encoded by this gene belongs to the ser/thr protein kinase family. It is the catalytic subunit of the 5-prime-AMP-activated protein kinase (AMPK). AMPK is a cellular energy sensor conserved in all eukaryotic cells. The kinase activity of AMPK is activated by the stimuli that increase the cellular AMP/ATP ratio. AMPK regulates the activities of a number of key metabolic enzymes through phosphorylation. It protects cells from stresses that cause ATP depletion by switching off ATP-consuming biosynthetic pathways. Alternatively spliced transcript variants encoding distinct isoforms have been observed. Protein kinase, AMP-activated, alpha 1 has been shown to interact with TSC2. GRCh38: Ensembl release 89: ENSG00000132356 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000050697 - Ensembl, May 2017 "Human PubMed Reference:". "Mouse PubMed Reference:". Stapleton D, ...
Autophagy is a process by which eukaryotic cells engulf and break down cellular components to provide new substrates for metabolism. Egan et al. (see the Perspective by Hardie) report a biochemical mechanism by which low energy stores in a cell can be linked to autophagy. The authors searched for targets of the adenosine monophosphate-activated protein kinase (AMPK), which is activated when cellular concentrations of adenosine triphosphate are depleted. AMPK was found to regulate another protein kinase, ULK1, which functions in regulation of autophagy. Cells engineered so that ULK1 could not be phosphorylated by AMPK failed to respond properly to starvation, had decreased autophagy, and were prone to starvation-induced cell death.. D. F. Egan, D. B. Shackelford, M. M. Mihaylova, S. Gelino, R. A. Kohnz, W. Mair, D. S. Vasquez, A. Joshi, D. M. Gwinn, R. Taylor, J. M. Asara, J. Fitzpatrick, A. Dillin, B. Viollet, M. Kundu, M. Hansen, R. J. Shaw, Phosphorylation of ULK1 (hATG1) by AMP-activated ...
5AMP-activated protein kinase (AMPK) can be activated in response to cellular fuel depletion and leads to switching off ATP-consuming pathways and switching on ATP-regenerating pathways in many cell types. We have hypothesized that AMPK is a central mediator of insulin-independent glucose transport, which enables fuel-depleted muscle cells to take up glucose for ATP regeneration under conditions of metabolic stress. To test this hypothesis, rat epitrochlearis muscles were isolated and incubated in vitro under several conditions that evoke metabolic stress accompanied by intracellular fuel depletion. Rates of glucose transport in the isolated muscles were increased by all of these conditions, including contraction (5-fold above basal), hypoxia (8-fold), 2,4-dinotrophenol (11-fold), rotenone (7-fold), and hyperosmolarity (8-fold). All of these stimuli simultaneously increased both alpha1 and alpha2 isoform-specific AMPK activity. There was close correlation between alpha1 (r2 = 0.72) and alpha2 ...
Mountjoy, P. D., Bailey, S. J. and Rutter, G. A., 2007. Inhibition by glucose or leptin of hypothalamic neurons expressing neuropeptide Y requires changes in AMP-activated protein kinase activity. Diabetologia, 50, pp. 168-177.. ...
AMPK is an energy sensor that protects cellular energy state by attenuating anabolic and promoting catabolic processes. AMPK signaling is purported to regulate hepatic gluconeogenesis and substrate oxidation; coordination of these processes is vital during nutrient deprivation or pathogenic during overnutrition. Here we directly test hepatic AMPK function in regulating metabolic fluxes that converge to produce glucose and energy in vivo. Flux analysis was applied in mice with a liver-specific deletion of AMPK (L-KO) or floxed control littermates to assess rates of hepatic glucose producing and citric acid cycle (CAC) fluxes. Fluxes were assessed in short and long term fasted mice; the latter condition is a nutrient stressor that increases liver AMP/ATP. The flux circuit connecting anaplerosis with gluconeogenesis from the CAC was unaffected by hepatic AMPK deletion in short and long term fasting. Nevertheless, depletion of hepatic ATP was exacerbated in L-KO mice, corresponding to a relative ...
5-AMP-activated protein kinase subunit beta-2 is an enzyme that in humans is encoded by the PRKAB2 gene. The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This subunit may be a positive regulator of AMPK activity. It is highly expressed in skeletal muscle and thus may have tissue-specific roles. 1q21.1 deletion syndrome 1q21.1 duplication syndrome PRKAB2 has been shown to interact with PRKAG2 and PRKAG1. Research on the genes CHD1L and PRKAB2 within lymphoblast cells lead to the ...
Biochemists at The Scripps Research Institute (TSRI) have discovered a genetic sequence that can alter its host genes activity in response to cellular energy levels. The scientists have found this particular energy-sensing switch in bacterial genes, which could make it a target for a powerful new class of antibiotics. If similar energy-sensing switches are also identified for human genes, they may be useful for treating metabolism-related disorders such as type 2 diabetes and heart disease. This discovery adds a new dimension to our understanding of how cells sense and manage their energy levels, which is one of the most important processes in biology, said the studys senior author, Martha J. Fedor, a professor the departments of Chemical Physiology and Molecular Biology and a member of the Skaggs Institute for Chemical Biology at TSRI.. The findings are described online ahead of print on October 21, 2012, in the journal Nature Chemical Biology.. A Fuel Sensor. This type of gene-switching ...
We read with interest the article by Lai and coworkers1 published in Circulation about the favorable cardiovascular and metabolic effects of inorganic nitrite and metformin in patients with pulmonary hypertension in heart failure with preserved ejection fraction. Accumulating studies have demonstrated the therapeutic effects of stimulating the nitrate-nitrite-nitric oxide (NO) pathway in renal, cardiovascular, and metabolic disorders. However, the underlying mechanisms are still being debated.. Patients with metabolic syndrome are generally considered to have a higher risk of developing pulmonary hypertension in heart failure with preserved ejection fraction. In this study, Lai et al use a novel animal model of combined metabolic syndrome and pulmonary hypertension in heart failure with preserved ejection fraction and demonstrate that long-term treatment with inorganic nitrate combined with nitrite for 12 weeks reduces pulmonary pressures and vascular remodeling and improves glycemic control. ...
Hurley, RL, Barre, LK, Wood, SD, Anderson, KA, Kemp, BE, Means, AR and Witters, LA (2006), Regulation of AMP-activated protein kinase by multi-site phosphorylation in response to agents that elevate cellular cAMP, J. Biol. Chem. 281, 36662-36672,. Barre, L, Richardson, C, Hirshman, MF, Brozinick, Fiering, S, Kemp, BE, Goodyear, LJ and Witters, LA (2007) A genetic model for the chronic activation of skeletal muscle AMP-activated protein kinase leads to glycogen accumulation, Am J Physiol Endo Metab, 292, E802-811. Gleason, CE, Lu, D, Witters, LA, Newgard, CB and Birnbaum, MJ, (2007) The role of AMPK and mTOR in nutrient sensing in pancreatic β-cells, J. Biol. Chem., 282, 10341-103451. Roecki, KSC, Hirshman, MF, Brandauer, J, Fujii, N.. Witters, LA and Goodyear, LJ (2007), Skeletal Muscle Adaptation to Exercise Training AMP-Activated Protein Kinase Mediates Muscle Fiber Type Shift, Diabetes, 56, 2062-2069. Anderson, KA, Riber, T, Lin, F, Noeldner, P, Green, M, Murhlbauer, MJ, Witters LA, Kemp, BE ...
If you have problems with a majority of the weight loss pillars, you might consider increasing the activity of a key cellular switch: AMPK (adenosine monophosphate-activated protein kinase). AMPK is… ...
Introduction: Protection of the heart from chemotherapeutic (Doxorubicin, DOX) drug-induced toxicity is a desirable goal, to limit side effects of cancer treatments. DOX toxicity has been linked to the activation (phosphorylation) of the AMP-activated kinase, AMPK. The 18 kDa low molecular weight isoform of fibroblast growth factor 2 (Lo-FGF-2) is a known cardioprotective and cytoprotective agent. In this study we have tested the ability of Lo-FGF-2 to protect from DOX-induced damage in rat cardiomyocytes in vitro, and in transgenic mouse models in vivo, in relation to AMPK activation.. Methods: Rat neonatal cardiomyocytes in culture were exposed to DOX (0.5 μM) in the presence or absence of pre-treatment Lo-FGF-2 (10 ng/ml). Compound C was used to block phosphorylation (activity) of AMPK. Levels of cell viability/death (using Calcein-AM/Propidium iodide assay), phospho -and total AMPK, and apoptotic markers such as active caspase 3 were analyzed. In addition, transgenic mice expressing only ...
The protein encoded by this gene is a catalytic subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. Studies of the mouse counterpart suggest that this catalytic subunit may control whole-body insulin sensitivity and is necessary for maintaining myocardial energy homeostasis during ischemia. [provided by RefSeq, Jul 2008 ...
0001 Vynález sa týka zlúčenin, ktoré sú priamymi aktivátormi AMPK (AMPaktivovanej proteínkinázy) a ich použitia pri liečení porúch regulovaných deaktiváciou AMPK. Napríklad zlúčeniny podľa vynálezu sú použiteľné naDoterajší stav techniky a úvod vynálezu0002 AMPK je dobre zavedený ako senzor a regulátor homeostázy bunkovej energie (Hardie D. G. a Hawley S. A., AMP-activated protein kinase the energy charge hypothesis revisited Bioassays, 23, 1112, (2001), Kemp B. E. a kol. AMP-activated protein kinase, super metabolic regulator, Biochem Soc. Transactions, 31. 162 (2003. Alosterická aktivácia tejto kinázy vdaka zvýšeniu množstva AMP vedie k stavom svyčerpaním bunkovej energie. Výsledná fosforylácia serínu/treoninu cieľových enzýmov vedie kadaptácii bunkového metabolizmu na nízkoenergetický stav. Celkový efekt zmien vyvolaných aktiváciou AMPK je inhibícia procesov spotrebovávajúcich ATP a aktivácia metabolických ciest vytvárajúcich ATP, a ...
Results Compared with the heart failure group, Resveratrol treatment group demonstrated a sharp decrease in mortality (p,0.01) and increase in left ventricular ejection fraction (LVEF) (46.84±6.06 vs 34.44±2.13 %, p,0.01). AMPK expression increased (p,0.05). Compared with wild type, LVPmax, +dP/dTmax, -dP/dTmax were significantly reduced in SIRT1 (+/-) mice (111.04±13.97 vs 141.90±6.63 mm Hg, 2944.33±461.02 vs 7122.73±1083.12 mm Hg/s, 2081.72±323.81 vs 4807.48±789.79 mm Hg/s, p,0.01 respectively), AMPK expression also decreased significantly in SIRT1 (+/-) mice hearts (p,0.01), Life of SIRT1 (+/-) mice is shorter than that of WT mice (p,0.01). Expression of SIRT1 and AMPK was significantly increased in H9c2 cells cultivated with resveratrol (50, 100 uM) as compared with control H9c2 cells (p,0.01), AMPK expression was significantly increased in H9c2 cells by SIRT1 overexpression (p,0.01), but reduced in groups of NAM (20, 40 mM) compared with control (p,0.01, respectively).. ...
Biochim Biophys Acta. 2013 Oct;1830(10):4743-51. doi: 10.1016/j.bbagen.2013.06.004. Epub 2013 Jun 18. Research Support, Non-U.S. Govt
The role of the AMPK in the regulation of vascular tone is presently controversial, because although AMPK has been linked to the phosphorylation of eNOS in cultured endothelial cells, no obvious defect in NO-mediated relaxation is evident in arteries from AMPKα1−/− or AMPKα2−/− mice (see above). That the activation of the AMPK in vivo is of benefit to cardiovascular function is assumed on the basis of observations that metformin improves vasodilator function127,128 and can prevent the progression of heart failure.129 However, whether these effects are dependent on eNOS activation or the modulation of other endothelium-dependent vasodilator/vasoconstrictor pathways are affected is presently unknown. The latter is certainly possible because metformin treatment decreases the production of an endothelium-derived vasoconstrictor prostanoid in a rat model of type 2 diabetes.130. Endothelium-dependent relaxation, however, is not exclusively regulated by NO and on the basis of the available ...
The tumor suppressor kinase LKB1 has been identified as a physiologic activator of the key metabolic regulator 5-AMP-activated protein kinase, establishing a possible molecular link between the...
How cancer cells adapt to metabolically adverse conditions in patients and strive to proliferate is a fundamental question in cancer biology. Here we show that AMP-activated protein kinase (AMPK), a metabolic checkpoint kinase, confers metabolic stress resistance to leukemia-initiating cells (LICs) and promotes leukemogenesis. Upon dietary restriction, MLL-AF9-induced murine acute myeloid leukemia (AML) activated AMPK and maintained leukemogenic potential. AMPK deletion significantly delayed leukemogenesis and depleted LICs by reducing the expression of glucose transporter 1 (Glut1), compromising glucose flux, and increasing oxidative stress and DNA damage. LICs were particularly dependent on AMPK to suppress oxidative stress in the hypoglycemic bone marrow environment. Strikingly, AMPK inhibition synergized with physiological metabolic stress caused by dietary restriction and profoundly suppressed leukemogenesis. Our results indicate that AMPK protects LICs from metabolic stress and that ...
PAULI, José Rodrigo; ROPELLE, Eduardo Rochete; CINTRA, Dennys Esper and SOUZA, Cláudio Teodoro de. Effects of physical exercise in the Ampkα expression and activity in high-fat diet induced obese rats. Rev Bras Med Esporte [online]. 2009, vol.15, n.2, pp.98-103. ISSN 1517-8692. http://dx.doi.org/10.1590/S1517-86922009000200003.. INTRODUCTION: High-fat diet is a special risk factor in the development of insulin resistance and type 2 diabetes. OBJECTIVE: To investigate the effects of physical exercise on the AMPK expression and activity in high-fat diet induced obese rats. METHODS: Wistar rats were randomly divided into four groups and received either a rat maintenance diet (control group) or an isocaloric high-fat diet (HFD) (sedentary groups and exercised groups) for four months. Two different exercise protocols were utilized: acute or chronic swimming exercise. Insulin tolerance test was performed to estimate whole-body insulin sensitivity. AMPKα and GLUT4 as well as p-AMPKα and pACC of ...
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AMP-activated protein kinase (AMPK) plays diverse roles and coordinates complex metabolic pathways for maintenance of energy homeostasis. This could be explained by the fact that AMPK exists as multiple heterotrimer complexes comprising a catalytic α subunit (α1, α2) and regulatory β (β1, β2) and γ (γ1, γ2, γ3) subunits, which are uniquely distributed across different cell types. There has been keen interest in developing specific and isoform-selective AMPK-activating drugs for therapeutic use and also as research tools. Moreover, establishing ways of enhancing cellular AMPK activity would be beneficial for both purposes. Here, we investigated if a recently-described potent AMPK-activator called 991, in combination with a commonly used activator AICAR or contraction, further enhances AMPK activity and glucose transport in mouse skeletal muscle ex vivo. Given that γ3 is exclusively expressed in skeletal muscle and is implicated in contraction-induced glucose transport, we measured the ...
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AMPK alpha 1 + AMPK alpha 2小鼠单克隆抗体[34.2](ab80039)可与小鼠, 大鼠, 人, 果蝇样本反应并经WB, IP, ELISA, IHC, ICC/IF实验严格验证,被4篇文献引用并得到5个独立的用户反馈。
AMPK is a metabolic "master switch", phosphorylating key target proteins that control flux through metabolic pathways of hepatic ketogenesis, cholesterol synthesis, lipogenesis, triglyceride synthesis, adipocyte lipolysis and skeletal muscle fatty acid oxidation.3 We hypothesised that genetic variation in the AMPK α2 subunit gene PRKAA2 is associated with regulation of the lipid profile, affecting body fat deposition and sensitivity of target organs to insulin, potentially mediated by differential expression or activity of the AMPK α2 subunit. To this end, we have examined association of a set of five tSNPs spanning the AMPK catalytic α2 subunit gene PRKAA2, with a range of phenotypes representing body fat, insulin sensitivity and lipids. Minor associations were observed with ApoB, triglyceride, HDL-cholesterol and measures of body fat, and none with the insulin-sensitivity parameters. Therefore, in this study sample, common variation in PRKAA2 does not seem to be responsible for changes in ...
cellular activities such as growth, differentiation, apoptosis, polarity, and migration must be coordinated with the availability of metabolic energy. 5′-AMP-activated protein kinase (AMPK) is the chief sensor of the fuel metabolism and cellular energy, switching on pathways that conserve or produce ATP (including glucose uptake, glycolysis, mitochondrial biogenesis, and fatty acid oxidation) and switching off ATP-consuming processes (such as synthesis of proteins, fatty acids, glycogen, or cholesterol) (9, 36). AMPK is a heterotrimeric enzyme consisting of an α-catalytic subunit with serine/threonine kinase activity, as well as β- and γ-regulatory subunits (9, 10, 38, 42). AMPK activity is typically regulated by decreased ATP levels, associated with an increased AMP:ATP ratio within cells. Under these conditions, the binding of AMP to the γ-subunit activates AMPK through a complex mechanism believed to involve an allosteric effect on the kinase that allows increased phosphorylation of the ...
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Abstract AMP-activated protein kinase (AMPK) is a stress signaling enzyme that orchestrates the regulation of energy-generating and -consuming pathways. Intrinsic AMPK activation p..
Buy our Recombinant human CDC42 binding protein kinase alpha. Ab59979 is an active protein fragment produced in Baculovirus infected Sf9 cells and has been…
where mN lumps various loss rates (e.g., maintenance, death) of the parasite.. This model requires a few other pieces of biology before use (see Hall et al. 2009a for the mathematical details). First, an equation for food dynamics follows our experimental protocol (below): non-reproducing food is consumed by hosts but replenished daily. Second, parasite growth within a host can inflict moderate and severe energetic stress on the host. As parasites draw down energy within a host, they can first stop growth of the host (moderate energetic stress), but then stop reproduction (severe energetic stress). These changes update the kappa-rule for allocation of utilized energy. Third, the parasite kills the host once it reaches a physical threshold (N = ρW, where ρ denotes a mechanical limit of the host to support the parasite). Once this threshold is crossed, the animal stops eating (i.e., f = 0). Then, energy reserve (E) drops to zero, and the host dies. (The parasite cannot drop E to zero itself ...
This work was to examine the effect of 3-methyl-4, 7-dihydroxyflavanone, a geranyl flavonoid (GF), on hepatocellular AMPK activity and lipid levels in HepG2 cells and diabetic mice, and identify molecular mechanism of the GF action on remedying dyslipidemia. The AMPK activation and lipid-lowering effect of the GF in diabetic mice and in HepG2 cells paralleled observations. The GF activated AMPK in HepG2 cells treated with high glucose, and enhance phosphorylation of ACC1 and ACC2, two isoforms of ACC, resulting in decrease in ACC activity and hepatic lipids. As demonstrated in cells overexpressing a dominant-negative AMPK mutant, the effect of GF was shown to be mediated by the activation of AMPK. The AMPK was activated relatively rapidly by GF and well before any potential change in adenosine triphosphate (ATP) level was detected. Thus, both in vivo and in vitro inhibition of AMPK, activation of ACC, and hepatocellular lipid accumulation caused by sustained high glucose levels was effectively
A breakthrough on how cells regulate their energy is promising for clinical gains into diseases such as obesity, diabetes and cancer. Researchers at McGill University and University of Pennsylvania have uncovered new insights into how a protein known as the AMP-activated protein kinase, or AMPK, a master regulator of metabolism, controls how our cells generate energy. AMPK has previously been linked to a number of biological functions including cancer, diabetes, and proper immune function.. In discovering these new functions of AMPK, researchers are one step closer to understanding how cells in the body manage their energy resources. The team discovered that AMPK plays a role in this process in part by directly modifying gene expression, acting as a type of cell energy "rheostat." Their findings are published in the journal Science.. McGill Professor Russell Jones, of the Rosalind and Morris Goodman Centre in the Department of Physiology in the Faculty of Medicine; Shelley Berger, PhD, Prof. ...
AMP-activated protein kinase (AMPK) functions as a sensor to maintain energy balance and is therefore a potential target for drug design against metabolic syndrome. The crystal structure of the complex between the phosphorylated-state mimic T172D mutant AMPK α2 kinase domain and a selective inhibitor, compound C, has been determined, revealing the unique inhibitor-binding mode of this protein kinase ...
The KOMP Repository is located at the University of California Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...
This study has several important findings. First, we confirm that inhibition of AMPK in the ischemic brain is beneficial. Second, the neuroprotection seen with AMPK inhibition is sustained for at least 1 week postinfarct. Third, continued neuroprotection is seen even after delayed administration of Compound C and C75. Finally, we demonstrate a significant role for AMPK α-2 isoform in the detrimental response of AMPK activation in ischemic brain, as deletion of this isoform leads to neuroprotection. The combination of pharmacological and genetic methods for inhibiting AMPK activity, combined with the use of relevant in vivo models of ischemia-reperfusion, strongly support our hypothesis that AMPK inactivation in the setting of ischemia is neuroprotective.. AMPK is a known regulator of cellular energy that functions to monitor cell-intrinsic processes that convey energy homeostasis.5-7 The discovery that the hypothalamus expressed high levels of AMPK, especially in nuclei that regulate energy ...
OADs with significant Cardio-protective benefit, improving whole body insulin sensitivity with anti-obesity and systemic anti-inflammatory benefits.. AMP-activated protein kinase is a systemic regulator of cellular energy(AMPK) homeostasis, coordinating anabolic and catabolic processes in glucose and lipid metabolism. AMPK exists as a trimer with specific combinations of the subunits and their isoforms in different tissues. Connexios program comprises specific and potent compounds which activate two sub-units of this trimeric complex, thus allowing the activation of the kinase across multiple metabolically relevant tissues.. ...
The ratio between ATP and AMP is used as a way for a cell to sense how much energy is available and control the metabolic pathways that produce and consume ATP. The body attempts to maintain a specific ratio of AMP:ATP; when this ratio is out of balance, the cells adjust their metabolism accordingly. As the ratio increases either by increased levels of AMP or decreased levels of ATP, the body is signaled to produced more ATP. The AMP:ATP ratio is primarily regulated by an enzyme known as AMP-activated protein kinase (AMPK). When activated, AMPK sets in motion a series of events which switch cells from active ATP consumption to ATP production ...
GW-501,516 (also known as GW1516 or GSK-516) is a drug developed by GlaxoSmithKline, which acts as a PPARδ modulator.[1][2] It activates AMP-activated protein kinase and stimulates glucose uptake in skeletal muscle tissue,[3] and has been demonstrated to reverse metabolic abnormalities in obese men with pre-diabetic metabolic syndrome, most likely by stimulating fatty acid oxidation.[4] It has been proposed as a potential treatment for obesity and related conditions,[5] especially when used in conjunction with a synergistic compound AICAR, as the combination has been shown to significantly increase exercise endurance in animal studies.[6][7] Concerns were raised prior to the 2008 Beijing Olympics that GW-501,516 or the GW-501,516 / AICAR combination could be used by athletes as a performance enhancing drug which was not currently controlled by regulations or detected by standard tests. One of the main researchers from the study on enhanced endurance consequently developed a urine test to detect ...
AMP-activated protein kinase is an evolutionarily conserved heterotrimeric enzyme whose primary role involves maintenance of energy balance in the eukaryotic cell. The structure and function of each of the subunits is conserved through evolution; however, although there are two or three genes encoding each subunit in the mammalian systems, there is but a single gene for each of them in Drosophila, making it an attractive model system to study the functions of AMPK in vivo (Pan and Hardie, 2002). Although it has been the focus of much research, little is known about the precise mechanisms underlying the regulatory functions of the β and γ subunits: β acts as a scaffold via its C-terminal domain and contains a carbohydrate-binding domain that associates the mammalian enzyme complex with glycogen, whereas the gamma subunit contains the so-called Bateman domains, responsible for binding of AMP and therefore allosteric activation of AMPK (Hardie, 2007). Finally, all three subunits are essential ...
A common factor underlies various health-promoting diets: an enzyme called AMP-activated protein kinase. Many botanicals also activate this enzyme
What causes us to lose muscle strength as we age and how exercise can prevent it from happening has never been thoroughly understood, but McMaster University researchers have discovered a key protein required to maintain muscle mass and muscle strength during aging. This important finding means new and existing drugs targeting the protein may potentially be used to preserve muscle function during aging.. "We found that the bodys fuel gauge, AMP-activated protein kinase (AMPK), is vital to slow muscle wasting with aging," said Gregory Steinberg, the studys senior author and professor of medicine at the Michael G. DeGroote School of Medicine. He is also co-director of MAC-Obesity, the Metabolism and Childhood Obesity Research Program at McMaster.. ...
Modules of approx. 100 residues with glycogen-binding function, appended to GH13 modules. Also found in the beta subunit (glycogen-binding) of AMP-activated protein kinases (AMPK ...
Oliveira SM, Zhang YH, Solis RS, Isackson H, Bellahcene M, Yavari A, Pinter K, Davies JK, Ge Y, Ashrafian H, et al. AMP-Activated Protein Kinase Phosphorylates Cardiac Troponin I and Alters Contractility of Murine Ventricular Myocytes. Circulation Research. 2012 ;110:1192-1201. ...
cite journal ,last=Viollet ,first=Benoît ,last2=Andreelli ,first2=Fabrizio ,last3=Jørgensen ,first3=Sebastian B. ,last4=Perrin ,first4=Christophe ,last5=Geloen ,first5=Alain ,last6=Flamez ,first6=Daisy ,last7=Mu ,first7=James ,last8=Lenzner ,first8=Claudia ,last9=Baud ,first9=Olivier ,last10=Bennoun ,first10=Myriam ,last11=Gomas ,first11=Emmanuel ,last12=Nicolas ,first12=Gaël ,last13=Wojtaszewski ,first13=Jørgen F.P. ,last14=Kahn1 ,first14=Axel ,last15=Carling ,first15=David ,last16=Schuit ,first16=Frans C. ,last17=Birnbaum ,first17=Morris J. ,last18=Richter ,first18=Erik A. ,last19=Burcelin ,first19=Rémy ,last20=Vaulont ,first20=Sophie ,display-authors=5 ,date=January 2003 ,title=The AMP-activated protein kinase α2 catalytic subunit controls whole-body insulin sensitivity ,url=http://www.jci.org/articles/view/16567 ,journal=The Journal of Clinical Investigation ,volume=111 ,issue=1 ,pages=91-8 ,doi=10.1172/JCI16567 ,pmc=151837 ,pmid=12511592 ,accessdate=2012-11-17 ...
Adenosine, Forebrain, Sleep, Eeg, Rats, Sleep Deprivation, Neurons, ATP, Brain, Eye, Eye Movement, Movement, Rapid Eye Movement, Membrane, Nitric Oxide, Wakefulness, Time, AMP, Amp-activated Protein Kinase, Biological Phenomena
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AMPK alpha 2山羊多克隆抗体(ab105028)可与小鼠, 大鼠, 人样本反应并经WB, sELISA实验严格验证。所有产品均提供质保服务,中国75%以上现货。
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DRP1 inhibition induces AMPK activity in BTICsa. Lysates of 387 and 3565 BTICs expressing NT control shRNA, shDrp1#1, or shDrp1#2 were immunoblotted with the in
PRKAG1 overexpression lysate, 0.1 mg. Transient overexpression lysate of protein kise, AMP-activated, gamma 1 non-catalytic subunit (PRKAG1), transcript variant 2
Homo sapiens CDC42 binding protein kinase alpha (DMPK-like) (CDC42BPA), transcript variant A, mRNA. (H00008476-R03) - Products - Abnova
A heatmap displaying the average residual DNA binding activities of 15 different TFs upon treatment with 125 nM of a panel of inhibitor compounds. The residual
Contraindicaciones del ampk. adversos, si bien la píldora del día después no presenta particulares indicaciones de uso, ni muchos efectos particulares,.
Purpose: AMP-activated protein kinase (AMPK) acts as an energy sensor to maintain energy homeostasis at the cellular level. It functions as a heterotrimeric protein which consists of one catalytic subunit (α1 or α2), one regulatory subunit (β1 or β2) and one AMP-binding subunits (γ1, γ2, or γ3). Each of these subunits has a specific role in regulating the activity and stability or localization of AMPK. Activation of the AMPK pathway has been demonstrated to be neuroprotective in both light damage and inherited retinal degeneration models. The goal of this study was to determine whether deletion of one of the catalytic subunits AMPK α2 allele in the retina will affect normal retinal function and morphology.. Methods: Chx10 cre: AMPK α2f/f mice are deficient of AMPK α2 in all retinal neurons and Müller glial cells. Retinal function was measured by electroretinography (ERG) and retinal structure was observed by Spectral domain Optical Coherence Tomography (SD-OCT). Western blots and real ...
Deacetylases such as sirtuins (SIRTs) convert NAD to nicotinamide (NAM). Nicotinamide phosphoribosyl transferase (Nampt) is the rate-limiting enzyme in the NAD salvage pathway responsible for converting NAM to NAD to maintain cellular redox state. Activation of AMP-activated protein kinase (AMPK) increases SIRT activity by elevating NAD levels. As NAM directly inhibits SIRTs, increased Nampt activation or expression could be a metabolic stress response. Evidence suggests that AMPK regulates Nampt mRNA content, but whether repeated AMPK activation is necessary for increasing Nampt protein levels is unknown. To this end, we assessed whether exercise training- or 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide (AICAR)-mediated increases in skeletal muscle Nampt abundance are AMPK dependent. One-legged knee-extensor exercise training in humans increased Nampt protein by 16% (P | 0.05) in the trained, but not the untrained leg. Moreover, increases in Nampt mRNA following acute exercise or AICAR
Title: The Role of 5-AMP-Activated Protein Kinase (AMPK) in Diabetic Nephropathy: A New Direction?. VOLUME: 5 ISSUE: 1. Author(s):K. Wyatt McMahon, Dora I. Zanescu, Vineeta Sood, Elmus G. Beale and Sharma S. Prabhakar. Affiliation:Division of Nephrology and Hypertension, Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.. Keywords:AMPK, diabetic nephropathy, enzyme regulation, molecular pathogenesis. Abstract: Diabetic nephropathy (DN) is a microvascular complication of diabetes that is characterized by proteinuria, glomerulosclerosis, and decreased kidney function ultimately leading to end stage renal disease; in fact, DN is the leading cause of end stage renal disease in the western world. Glycemic and blood pressure control are currently the most common forms of prevention and treatment of the disease. However, despite good glycemic and blood pressure control, many patients still progress to end stage renal disease and require renal ...
Visfatin is an adipokine highly expressed in visceral AT (adipose tissue) of humans and rodents, the production of which seems to be dysregulated in excessive fat accumulation and conditions of insulin resistance. EPA (eicosapentaenoic acid), an n−3 PUFA (polyunsaturated fatty acid), has been demonstrated to exert beneficial effects in obesity and insulin resistance conditions, which have been further linked to its reported ability to modulate adipokine production by adipocytes. TNF-α (tumour necrosis factor-α) is a pro-inflammatory cytokine whose production is increased in obesity and is involved in the development of insulin resistance. Control of adipokine production by some insulin-sensitizing compounds has been associated with the stimulation of AMPK (AMP-activated protein kinase). The aim of the present study was to examine in vitro the effects of EPA on visfatin production and the potential involvement of AMPK both in the absence or presence of TNF-α. Treatment with the ...
Our study finds that coffee consumption or ex vivo treatment of cells with caffeine significantly improves migration of ECs and EPCs by an AMPK-dependent mechanism. Importantly, AMPK also contributed to the enhanced reendothelialization induced by caffeine in vivo. The beneficial influence of caffeine on reendothelialization seen in the mouse model could be explained by both migration of mature ECs as well as attachment of circulating EPCs, accelerating recovery of the endothelial monolayer. Several studies have documented the fundamental role of EPCs in the healing process of vascular endothelium alone,26 after mobilization with GM-colony stimulating factor (CSF),27 erythropoietin,28 or pretreatment with statins,3 estrogen29,30 or the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone.31 So far, two studies have investigated a potential role of AMPK for migration at least in mature ECs. Nagata et al have shown that overexpression of a dominant-negative mutant of the AMPK ...
Epidemiological studies have shown that infants exposed to an increased supply of nutrients before birth are at increased risk of type 2 diabetes in later life. We have investigated the hypothesis that fetal overnutrition results in reduced expression and phosphorylation of the cellular fuel sensor, AMP-activated kinase (AMPK) in liver and skeletal muscle before and after birth. From 115 days gestation, ewes were fed either at or 55% above maintenance energy requirements. Postmortem was performed on lamb fetuses at 139-141 days gestation (n = 14) and lambs at 30 days of postnatal age (n = 21), and liver and quadriceps muscle were collected at each time point. The expression of AMPK1 and AMPK2 mRNA was determined by quantitative RT-PCR (qRT-PCR). The abundance of AMPK and phospho-AMPK (P-AMPK) was determined by Western blot analysis, and the proportion of the total AMPK pool that was phosphorylated in each sample (%P-AMPK) was determined. The ratio of AMPK2 to AMPK1 mRNA expression was lower in ...
Half of the worlds population experiences Helicobacter pylori (H. pylori) infection, which is a main cause of gastritis, duodenal and gastric ulcer, and gastric cancers. In the current study, we investigated the potential role of compound 13 (C13), a novel α1-selective small molecule activator of AMP-activated protein kinase (AMPK), against H. pylori-induced cytotoxicity in cultured gastric epithelial cells (GECs). We found that C13 induced significant AMPK activation, evidenced by phosphorylation of AMPKα1 and ACC (acetyl-CoA carboxylase), in both primary and transformed GECs. Treatment of C13 inhibited H. pylori-induced GEC apoptosis. AMPK activation was required for C13-mediated GEC protection. Inhibition of AMPK kinase activity by the AMPK inhibitor Compound C, or silencing AMPKα1 expression by targeted-shRNAs, alleviated C13-induced GEC protective activities against H. pylori. Significantly, C13 inhibited H. pylori-induced reactive oxygen species (ROS) production in GECs. C13 induced ...
Activated AMPK promotes all the processes needed to maintain a youthful profile. However, AMPK activity fades with age. As previously mentioned, AMPK is activated in the presence of increased AMP. Therefore, to test the anti-aging properties of AMPK, researchers used fruit flies that were genetically engineered to synthesize higher levels of AMP. The research found that the modified flies lived up to one-third longer as a result of increased AMPK activity. "The life span benefit of these mutations depends upon increased AMP:ATP and ADP:ATP ratios and adenosine monophosphate-activated protein kinase (AMPK). Transgenic expression of AMPK in adult fat body or adult muscle, key metabolic tissues, extended life span" (Stenesen, 2013 ...
Liver kinase B1 (LKB1), known as a serine/threonine kinase, has been identified as a critical cancer suppressor in many cancer cells. It is a master upstream kinase of 13 AMP-activated protein kinase (AMPK)-related protein kinases, and possesses versatile biological functions. LKB1 gene is mutated in many cancers, and its protein can form different protein complexes with different cellular localizations in various cell types. The expression of LKB1 can be regulated through epigenetic modification, transcriptional regulation and post-translational modification. LKB1 dowcnstream pathways mainly include AMPK, microtubule affinity regulating kinase (MARK), salt-inducible kinase (SIK), sucrose non-fermenting protein-related kinase (SNRK) and brain selective kinase (BRSK) signalings, etc. This review, therefore, mainly discusses recent studies about the expression, regulation, downstream signaling and cancer suppressive function of LKB1, which can be helpful for better understanding of this molecular and
The metabolic sensor, AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase existing as a heterotrimer of catalytic (α1/α2) and regulatory subunits (β1/β2 and γ1/γ2/γ3). The 12 possible heterotrimers exhibit tissue and potentially functional specificity [8], and all can be activated by binding of AMP/ADP to the AMPKγ subunit and phosphorylation by one of two upstream kinases, liver kinase B (LKB)1 or calcium/calmodulin-dependent protein kinase kinase (CaMKK)β. AMPK is activated in response to depletion of ATP or alterations in intracellular calcium concentrations, and acts to shut down ATP-consuming, anabolic pathways and promoting ATP-generating, catabolic pathways [9].. As a monitor of cellular and whole body energy status [10], it is probably unsurprising that a recent elegant study in Science from Reuben Shaws laboratory places AMPK at the heart of the regulation of mitochondrial dynamics. Using CRISPR modification to delete AMPKα1 and/or AMPKα2 in vitro, they ...
AMP-activated protein kinase (AMPK) is a serine threonine kinase that is highly conserved through evolution. AMPK system acts as a sensor of cellular energy status. It is activated by increases in the cellular AMP:ATP ratio caused by metabolic stresses that either interfere with ATP production (eg, deprivation for glucose or oxygen) or that accelerate ATP consumption (eg, muscle contraction). Several upstream kinases, including liver kinase B1 (LKB1), calcium/calmodulin kinase kinase-beta (CaMKK beta), and TGF-beta-activated kinase-1 (TAK-1), can activate AMPK by phosphorylating a threonine residue on its catalytic alpha-subunit. Once activated, AMPK leads to a concomitant inhibition of energy-consuming biosynthetic pathways, such as protein, fatty acid and glycogen synthesis, and activation of ATP-producing catabolic pathways, such as fatty acid oxidation and glycolysis ...
NK cells are the first line of defense against infected and transformed cells. Defective NK cell activity was shown to increase susceptibility for viral infections and reduce tumor immune-surveillance. With age, the incidence of infectious diseases and malignancy rises dramatically, suggesting that impaired NK cell function might contribute to disease in these individuals. We found an increased frequency of NK cells with high expression of the inhibitory killer cell lectin-like receptor G1 (KLRG1) in individuals |70 y. The role of KLRG1 in ageing is not known, and the mechanism of KLRG1-induced inhibition of NK cell function is not fully understood. We report that NK cells with high KLRG1 expression spontaneously activate the metabolic sensor AMP-activated protein kinase (AMPK) and that activation of AMPK negatively regulates NK cell function. Pre-existing AMPK activity is further amplified by ligation of KLRG1 in these cells, which leads to internalization of the receptor and allows interaction with
Indole Derivatives Isolated from Brown Alga Sargassum thunbergii Inhibit Adipogenesis through AMPK Activation in 3T3-L1 Preadipocytes. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
BACKGROUND: Insulin-induced microvascular recruitment is important for optimal muscle glucose uptake. 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR, an activator of AMP-activated protein kinase), can also induce microvascular recruitment, at doses that do not acutely activate glucose transport in rat muscle. Whether low doses of AICAR can augment physiologic insulin action is unknown. In the present study we used the euglycemic hyperinsulinemic clamp to assess whether insulin action is augmented by low dose AICAR. METHODS: Anesthetized rats were studied during saline infusion or euglycemic insulin (3 mU/kg/min) clamp for 2 h in the absence or presence of AICAR for the last hour (5 mg bolus followed by 3.75 mg/kg/min). Muscle glucose uptake (Rg) was determined radioisotopically with (14)C-2-deoxyglucose and muscle microvascular perfusion by contrast-enhanced ultrasound with microbubbles. RESULTS: AICAR did not affect blood glucose, or lower leg Rg, although it significantly (p | 0.05)
Skeletal muscle is a major insulin-target tissue and plays an important role in glucose homeostasis. Impaired insulin action in muscles leads to insulin resistance and type 2 diabetes mellitus. 5′ AMP-activated kinase (AMPK) is an energy sensor, its activation increases glucose uptake in skeletal muscle and AMPK activators have been viewed as a targeted approach in combating insulin resistance. We previously reported AMPK activation and increased muscle glucose uptake by rosemary extract (RE). In the present study, we examined the effects and the mechanism of action of rosmarinic acid (RA), a major RE constituent, in L6 rat muscle cells. RA (5.0 μM) increased glucose uptake (186 ± 4.17% of control, p , 0.001) to levels comparable to maximum insulin (204 ± 10.73% of control, p , 0.001) and metformin (202 ± 14.37% of control, p , 0.001). Akt phosphorylation was not affected by RA, while AMPK phosphorylation was increased. The RAstimulated glucose uptake was inhibited by the AMPK inhibitor ...
Our previous studies have shown that acetaminophen (APAP)-induced hepatocyte necrosis is mediated by JNK. In the present study we show that protein kinase C (PKC) plays an important role in APAP-induced liver injury through JNK-dependent and independent pathways. Treatment of primary mouse hepatocytes with two different broad-spectrum PKC inhibitors (Ro-31-8245, Go6983), protected against APAP hepatotoxicity without inhibiting JNK activation. Ro-31-8245 treatment to mice also resulted in upregulation of p-AMPK in the liver and protection against APAP-induced liver injury in vivo, despite sustained JNK activation. APAP treatment caused a decreased p-AMPK, which was prevented by broad-spectrum PKC inhibitors. AMPK inhibition by compound C or activation using AMPK activator oppositely modulated APAP hepatotoxicity. This suggests PKC-dependent downregulation of AMPK-regulated survival pathways is an important component of APAP hepatotoxicity. In contrast to broad-spectrum inhibitors, treatment of ...
Cerebral ischemia is the second-leading cause of death and the main cause of permanent adult disabilities worldwide. Qingkailing (QKL) injection, a patented Chinese medicine approved by the China Food and Drug Administration, has been widely used in clinical practice to treat cerebral ischemia in China. The NOD-like receptor pyrin 3 (NLRP3) inflammasome is activated in cerebral ischemia and thus, is an effective therapeutic target. AMP-activated protein kinase (AMPK) is an important regulator inhibiting NLRP3 inflammasome activation. We investigated the potential of QKL injection to provide neuroprotection after cerebral ischemia in a rat model of middle cerebral artery occlusion (MCAO). Adult male Sprague-Dawley rats (210-230 g) were randomly divided into three groups which consist of sham, MCAO and 3 ml/kg QKL. Rats in the QKL group received intraperitoneal injections of 3 ml/kg QKL, while rats in other groups were given saline in the same volumes. After 90 min ischemia and 24 h reperfusion,
Research continues to reveal that consuming grapefruit benefits weight loss in a a major way.† The key may be an enzyme called AMP-activated protein kinase (AMPK), which appears to get activated by an organic compound in grapefruit called nootkatone. When AMPK gets activated, it encourages the bodys energy-producing processes, like glucose uptake, for example, which helps boost metabolism. That, in turn, can encourage weight loss. AMPK is generally activated during exercise to help muscles use stored sugar and fat for energy.. An animal study published in the American Journal of Physiology-Endocrinology and Metabolism demonstrated how long-term intake of nootkatone "significantly reduced high-fat and high-sucrose diet-induced body weight gain, abdominal fat accumulation, and the development of hyperglycemia, hyperinsulinemia, and hyperleptinemia." The study concluded that not only can grapefruits nootkatone likely help to prevent obesity, but it can also improve overall physical ...
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Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase...Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase...

F. Y. L. Li, K. S. L. Lam, H.-F. Tse et al., "Endothelium-selective activation of AMP-activated protein kinase prevents ... The specific signal pathways of AMP-activated protein kinase (AMPK), eNOS/Akt, and heme oxygenase-1 (HO-1) were also assessed. ... D. Kukidome, T. Nishikawa, K. Sonoda et al., "Activation of AMP-activated protein kinase reduces hyperglycemia-induced ... Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase ...
more infohttps://www.hindawi.com/journals/jdr/2016/6384759/

AMP-Activated Protein Kinase: Potential Target for TNBCAMP-Activated Protein Kinase: Potential Target for TNBC

AMP-activated protein kinase (AMPK), an energy sensor, can regulate protein and lipid metabolism responding to alterations in ... AMP-Activated Protein Kinase. A Potential Therapeutic Target for Triple-Negative Breast Cancer. ...
more infohttps://www.medscape.com/viewarticle/910480

Dealing with energy demand: the AMP-activated protein kinase.  - PubMed - NCBIDealing with energy demand: the AMP-activated protein kinase. - PubMed - NCBI

The AMP-activated protein kinase (AMPK) is a member of a metabolite-sensing protein kinase family that is found in all ... Dealing with energy demand: the AMP-activated protein kinase.. Kemp BE1, Mitchelhill KI, Stapleton D, Michell BJ, Chen ZP, ... SNF1-related protein kinases. *Protein-Serine-Threonine Kinases. *AMP-Activated Protein Kinases ... Protein Kinases/chemistry. *Protein Kinases/metabolism*. *Protein-Serine-Threonine Kinases/chemistry. *Protein-Serine-Threonine ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/10087918?dopt=Abstract

The AMP-activated protein kinase beta 1 subunit modulates erythrocyte integrity.  - PubMed - NCBIThe AMP-activated protein kinase beta 1 subunit modulates erythrocyte integrity. - PubMed - NCBI

The heterotrimeric AMP-activated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase that acts as a ... The AMP-activated protein kinase beta 1 subunit modulates erythrocyte integrity.. Cambridge EL1, McIntyre Z1, Clare S1, Arends ... B) Immunoblot analysis of AMPK subunits in Prkab1+/+ and Prkab1tm1b/tm1b spleen protein lysates. *IgG heavy chain. (C) White ... AMP-Activated Protein Kinases/genetics*. *AMP-Activated Protein Kinases/metabolism*. *Anemia, Hypochromic/genetics ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed?cmd=search&term=Reviriego+CB%5Bau%5D&dispmax=50

Nicotine Induces Negative Energy Balance Through Hypothalamic AMP-Activated Protein Kinase | DiabetesNicotine Induces Negative Energy Balance Through Hypothalamic AMP-Activated Protein Kinase | Diabetes

Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 2002;415:339-343pmid:11797013. ... AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab 2005;1:15- ... Nicotine Induces Negative Energy Balance Through Hypothalamic AMP-Activated Protein Kinase. Pablo B. Martínez de Morentin, ... Nicotine Induces Negative Energy Balance Through Hypothalamic AMP-Activated Protein Kinase. Pablo B. Martínez de Morentin, ...
more infohttp://diabetes.diabetesjournals.org/content/61/4/807.long

Images under the category AMP-activated protein kinase | Clinical ScienceImages under the category AMP-activated protein kinase | Clinical Science

Role of AMP-activated protein kinase in adipose tissue metabolism and inflammation. Silvia Bijland, Sarah J. Mancini, Ian P. ... Role of AMP-activated protein kinase in adipose tissue metabolism and inflammation. Silvia Bijland, Sarah J. Mancini, Ian P. ... Production of these adipocytokines is promoted by activated AMPK. Excess calorie intake leads to the development of a pro- ... ATP-consumption during re-esterification of FAs after lipolysis may also activate AMPK (3), such that regulation of lipolysis ...
more infohttp://www.clinsci.org/image-gallery/amp-activated-protein-kinase

PRKAA1 (protein kinase AMP-activated catalytic subunit alpha 1)PRKAA1 (protein kinase AMP-activated catalytic subunit alpha 1)

... protein kinase AMP-activated catalytic subunit alpha 1), Authors: Esin Gülce Seza, Ismail Güderer, Çagdas Ermis, Sreeparna ... kinase activity AMP-activated protein kinase activity AMP-activated protein kinase activity AMP-activated protein kinase ... kinase activity AMP-activated protein kinase activity AMP-activated protein kinase activity AMP-activated protein kinase ... nucleotide-activated protein kinase complex nucleotide-activated protein kinase complex nucleotide-activated protein kinase ...
more infohttp://atlasgeneticsoncology.org/Genes/PRKAA1ID43428ch5p13.html

5 AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle. | Diabetes5' AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle. | Diabetes

5 AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle.. ... 5 AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle. ... 5 AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle. ... 5 AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle. ...
more infohttp://diabetes.diabetesjournals.org/content/48/8/1667?ijkey=5a9b045ad960ea147b817f216d012a817077438e&keytype2=tf_ipsecsha

WikiGenes - PRKAB2 - protein kinase, AMP-activated, beta 2 non...WikiGenes - PRKAB2 - protein kinase, AMP-activated, beta 2 non...

Synonyms: 5-AMP-activated protein kinase subunit beta-2, AMPK subunit beta-2 ... wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary ... knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound ... PRKAB2 - protein kinase, AMP-activated, beta 2 non.... Homo sapiens. ...
more infohttps://www.wikigenes.org/e/gene/e/5565.html

PRKAG3 - AMP-activated protein kinase gamma subunit - Bos taurus (Bovine) - PRKAG3 gene & proteinPRKAG3 - AMP-activated protein kinase gamma subunit - Bos taurus (Bovine) - PRKAG3 gene & protein

AMP-activated protein kinase gamma subunitImported. Automatic assertion inferred from database entriesi ... tr,Q4G3U3,Q4G3U3_BOVIN AMP-activated protein kinase gamma subunit OS=Bos taurus OX=9913 GN=PRKAG3 PE=4 SV=1 ... AMP-activated protein kinase gamma 3 non-catalytic subunit. CAPHI. 464. 5-AMP-activated protein kinase subunit gamma-3. SHEEP ... AMP-activated protein kinase subunit gamma-3. BOVIN. 497. UniRef90_Q2LL38. 5-AMP-activated protein kinase subunit gamma-3. ...
more infohttps://www.uniprot.org/uniprot/Q4G3U3

AMP-activated protein kinase - WikipediaAMP-activated protein kinase - Wikipedia

"AMP-activated protein kinase kinase activity and phosphorylation of AMP-activated protein kinase in contracting muscle of ... 5 AMP-activated protein kinase or AMPK or 5 adenosine monophosphate-activated protein kinase is an enzyme (EC 2.7.11.31) that ... It should not be confused with cyclic AMP-activated protein kinase (protein kinase A). AMPK is a heterotrimeric protein complex ... "Endurance training increases LKB1 and MO25 protein but not AMP-activated protein kinase kinase activity in skeletal muscle". Am ...
more infohttps://en.wikipedia.org/wiki/AMP-activated_protein_kinase

PRKAB1 (protein kinase, AMP-activated, beta 1 non-catalytic subunit)PRKAB1 (protein kinase, AMP-activated, beta 1 non-catalytic subunit)

AMP-activated, beta 1 non-catalytic subunit), Authors: Monserrat Sanchez-Cespedes. Published in: Atlas Genet Cytogenet Oncol ... protein kinase activity AMP-activated protein kinase activity protein binding nucleus nucleoplasm cytoplasm cytosol protein ... protein kinase activity AMP-activated protein kinase activity protein binding nucleus nucleoplasm cytoplasm cytosol protein ... PRKAB1 has a molecular mass of 30382 Da; This protein constitutes a regulatory subunit of the AMP-activated protein kinase ( ...
more infohttp://atlasgeneticsoncology.org/Genes/PRKAB1ID44100ch12q24.html

New targets of AMP-activated protein kinase | Biochemical Society TransactionsNew targets of AMP-activated protein kinase | Biochemical Society Transactions

AMPK 2002: 2nd International Meeting on AMP-activated Protein Kinase. New targets of AMP-activated protein kinase. L. Hue, C. ... protein synthesis. Footnotes. *. AMPK 2002: 2nd International Meeting on AMP-activated Protein Kinase, a Biochemical Society- ... New targets of AMP-activated protein kinase. L. Hue, C. Beauloye, L. Bertrand, S. Horman, U. Krause, A.-S. Marsin, D. Meisse, D ... AMP-activated protein kinase; AICAR, 5-amino-4-imidazolecar-boxamide riboside; PFK-1, 6-phosphofructo-1-kinase; iPFK-2, ...
more infohttp://www.biochemsoctrans.org/content/31/1/213

Crystal Structures of the Adenylate Sensor from Fission Yeast AMP-Activated Protein Kinase | ScienceCrystal Structures of the Adenylate Sensor from Fission Yeast AMP-Activated Protein Kinase | Science

The 5′-AMP (adenosine monophosphate)-activated protein kinase (AMPK) coordinates metabolic function with energy availability by ... Crystal Structures of the Adenylate Sensor from Fission Yeast AMP-Activated Protein Kinase ... Crystal Structures of the Adenylate Sensor from Fission Yeast AMP-Activated Protein Kinase ... Crystal Structures of the Adenylate Sensor from Fission Yeast AMP-Activated Protein Kinase ...
more infohttp://science.sciencemag.org/content/315/5819/1726

Expression of AMP-activated Protein Kinase (AMPK) Protein in Lung Adenocarcinoma - Full Text View - ClinicalTrials.govExpression of AMP-activated Protein Kinase (AMPK) Protein in Lung Adenocarcinoma - Full Text View - ClinicalTrials.gov

AMP-activated protein kinase (AMPK) is an evolutionally conserved protein kinase that serves as an energy guardian to help ... Expression of AMP-activated Protein Kinase (AMPK) Protein in Lung Adenocarcinoma. The safety and scientific validity of this ... Expression of AMP-activated Protein Kinase (AMPK) Protein in Lung Adenocarcinoma. Study Start Date :. September 2010. ...
more infohttps://clinicaltrials.gov/ct2/show/NCT01249066?cond=%22Adenocarcinoma+of+lung%22&rank=2

AMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan | SpringerLinkAMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan | SpringerLink

Adenosine monophosphate-activated protein kinase (AMPK) is a crucial regulator of energy metabolic homeostasis and thus a major ... Sun W, Lee TS, Zhu M, Gu C, Wang Y, Zhu Y, Shyy JYJ (2006) Statins activate AMP-activated protein kinase in vitro and in vivo. ... is necessary for thrombin-induced NF-κB activation in endothelial cells through AMP-activated protein kinase and protein kinase ... Activation of protein phosphatase 2A by palmitate inhibits AMP-activated protein kinase. J Biol Chem 282:9777-9788PubMed ...
more infohttps://link.springer.com/article/10.1007%2Fs00109-011-0748-0

Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase...Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase...

F. Y. L. Li, K. S. L. Lam, H.-F. Tse et al., "Endothelium-selective activation of AMP-activated protein kinase prevents ... D. Kukidome, T. Nishikawa, K. Sonoda et al., "Activation of AMP-activated protein kinase reduces hyperglycemia-induced ... Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase ... inhibition by the AMP-activated protein kinase activation," Diabetes, vol. 51, no. 1, pp. 159-167, 2002. View at Publisher · ...
more infohttps://www.hindawi.com/journals/jdr/2016/6384759/ref/

Prkab2 - 5-AMP-activated protein kinase subunit beta-2 - Mus musculus (Mouse) - Prkab2 gene & proteinPrkab2 - 5'-AMP-activated protein kinase subunit beta-2 - Mus musculus (Mouse) - Prkab2 gene & protein

... an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of ... Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. ... intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, ... Non-catalytic subunit of AMP-activated protein kinase (AMPK), ... 5-AMP-activated protein kinase subunit beta-2Add BLAST. 271. ...
more infohttp://www.uniprot.org/uniprot/Q6PAM0

Protein kinase, AMP-activated, alpha 1 - WikipediaProtein kinase, AMP-activated, alpha 1 - Wikipedia

"Stimulation of glucose transport by AMP-activated protein kinase via activation of p38 mitogen-activated protein kinase". J. ... 1996). "Characterization of the AMP-activated protein kinase kinase from rat liver and identification of threonine 172 as the ... Bolster DR, Crozier SJ, Kimball SR, Jefferson LS (2002). "AMP-activated protein kinase suppresses protein synthesis in rat ... AMP-activated protein kinase catalytic subunit alpha-1 is an enzyme that in humans is encoded by the PRKAA1 gene. The protein ...
more infohttps://en.wikipedia.org/wiki/Protein_kinase,_AMP-activated,_alpha_1

Mechanical stretch activates mammalian target of rapamycin and AMP-activated protein kinase pathways in skeletal muscle cells |...Mechanical stretch activates mammalian target of rapamycin and AMP-activated protein kinase pathways in skeletal muscle cells |...

... and AMP-activated protein kinase (AMPK) signaling pathways. In the present study, we... ... Cellular protein synthesis is believed to be antagonistically regulated by mammalian target of rapamycin (mTOR) ... Mechanical stretch activates mammalian target of rapamycin and AMP-activated protein kinase pathways in skeletal muscle cells. ... Bolster DR, Crozier SJ, Kimball SR, Jefferson LS (2002) AMP-activated protein kinase suppresses protein synthesis in rat ...
more infohttps://link.springer.com/article/10.1007/s11010-015-2446-7

Metformin Protects Against Systolic Overload-Induced Heart Failure Independent of AMP-Activated Protein Kinase α2 | HypertensionMetformin Protects Against Systolic Overload-Induced Heart Failure Independent of AMP-Activated Protein Kinase α2 | Hypertension

Activation of AMP-activated protein kinase (AMPK)-α2 protects the heart against pressure overload-induced heart failure in mice ... Metformin Protects Against Systolic Overload-Induced Heart Failure Independent of AMP-Activated Protein Kinase α2. Xin Xu, ... Metformin Protects Against Systolic Overload-Induced Heart Failure Independent of AMP-Activated Protein Kinase α2 ... Metformin Protects Against Systolic Overload-Induced Heart Failure Independent of AMP-Activated Protein Kinase α2 ...
more infohttp://hyper.ahajournals.org/content/early/2014/01/13/HYPERTENSIONAHA.113.02619

AMP-activated protein kinase: regulating cellular and whole body energy balance | HSTalksAMP-activated protein kinase: regulating cellular and whole body energy balance | HSTalks

Grahame Hardie on AMP-activated protein kinase: regulating cellular and whole body energy balance, part of a collection of ... AMP-activated protein kinase: regulating cellular and whole body energy balance. *Prof. Grahame Hardie - University of Dundee, ... AMP-activated protein kinase: regulating cellular and whole body energy balance. Embed in course/own notes ... Hardie, G. (2010, November 30). AMP-activated protein kinase: regulating cellular and whole body energy balance [Video file]. ...
more infohttps://hstalks.com/t/1890/amp-activated-protein-kinase-regulating-cellular-a/?biosci

Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy | SciencePhosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy | Science

Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy ... Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy ... Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy ... Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy ...
more infohttps://science.sciencemag.org/content/331/6016/456/tab-article-info

Role of AMP-activated protein kinase in adipose tissue metabolism and inflammation | Clinical ScienceRole of AMP-activated protein kinase in adipose tissue metabolism and inflammation | Clinical Science

... phosphoinositide 3-kinase; PKA, cAMP-dependent protein kinase; PKB, protein kinase B; PPAR, peroxisome-proliferator-activated ... AMP-activated protein kinase; aP2, adipocyte-specific fatty acid-binding protein; AS160, Akt substrate of 160 kDa; ATGL, ... Role of AMP-activated protein kinase in adipose tissue metabolism and inflammation. Silvia Bijland, Sarah J. Mancini, Ian P. ... AMPK (AMP-activated protein kinase) is a key regulator of cellular and whole-body energy balance. AMPK phosphorylates and ...
more infohttp://www.clinsci.org/content/124/8/491

British Library EThOS: Structural and functional studies on nucleotide binding to AMP-activated protein kinaseBritish Library EThOS: Structural and functional studies on nucleotide binding to AMP-activated protein kinase

AMP-activated protein kinase (AMPK) is an enzyme that senses and regulates cellular energy balance thus playing a key role in ... Structural and functional studies on nucleotide binding to AMP-activated protein kinase ... AMPK is primarily activated by phosphorylation at Thr-172 on the activation loop in the kinase domain. It exerts its cellular ... an intermediate on the biosynthetic route to AMP, the fluorescence reporter mant-AMP and the WPW mutants Arg298\rightarrowGly, ...
more infohttp://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.565036
  • The protein is dysregulated in several human diseases including diabetes and metabolic syndrome, cardiovascular diseases, neurodegenerative diseases and many cancer types (Steinberg and Kemp, 2009). (atlasgeneticsoncology.org)
  • The crystal structure of a key metabolic regulator reveals how it senses the ratio of ATP to AMP, initiating feedback processes to optimize ATP levels in the cell. (sciencemag.org)
  • I have also determined the structure of the regulatory fragment of the enzyme bound to 5-aminoimidazole-4-carboximide riboside monophosphate (ZMP), an intermediate on the biosynthetic route to AMP, the fluorescence reporter mant-AMP and the WPW mutants Arg298\rightarrowGly, Arg69\rightarrowGln and His150\rightarrowArg. (bl.uk)
  • It belongs to a highly conserved eukaryotic protein family and its orthologues are SNF1 and SnRK1 in yeast and plants, respectively. (wikipedia.org)
  • For example, lipopolysaccharide (LPS), a well-known PAMP expressed on Gram-negative bacteria, binds to and activates toll-like receptor 4 leading to the upregulation of critical inflammasome components (e.g. (frontiersin.org)
  • It also increases the expression of uncoupling proteins and the transcriptional regulator peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC1alpha), which could possibly increase energy expenditure. (garvan.org.au)
  • Mutations of two protein trafficking motifs within the 38-amino acid region in CFTR each disrupted the interaction. (jci.org)
  • Asn supplementation also increased the ratios of RNA:DNA and protein:DNA as well as disaccharidase activities in intestinal mucosa. (cambridge.org)
  • In this study, we aimed to investigate this issue in lipopolysaccharide-activated murine macrophages. (frontiersin.org)
  • One of the most extensively investigated inflammasomes is nucleotide and oligomerization domain, leucine-rich repeat containing protein family, pyrin containing domain 3 (NLRP3) in innate immune cells including macrophages. (frontiersin.org)
  • The majority of proteins playing essential biological roles undergo post-translational modification (PTM) to regulate their structure, cellular localization, activity and biological function. (frontiersin.org)