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.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
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.
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.
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)
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
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).
Agents that inhibit PROTEIN KINASES.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
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.
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.
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.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
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.
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.
The rate dynamics in chemical or physical systems.
Established cell cultures that have the potential to propagate indefinitely.
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.
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 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.
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.
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).
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.
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.
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.
An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
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.
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)
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)
A specific protein kinase C inhibitor, which inhibits superoxide release from human neutrophils (PMN) stimulated with phorbol myristate acetate or synthetic diacylglycerol.
A butyl-diphenyl-pyrazolidinedione that has anti-inflammatory, antipyretic, and analgesic activities. It has been used in ANKYLOSING SPONDYLITIS; RHEUMATOID ARTHRITIS; and REACTIVE ARTHRITIS.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
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.
Proteins prepared by recombinant DNA technology.
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.
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.
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.
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.
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.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
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.
An enzyme that catalyzes the deamination of AMP to IMP. EC 3.5.4.6.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
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).
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.
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
A group of phenyl benzopyrans named for having structures like FLAVONES.
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.
The relationship between the dose of an administered drug and the response of the organism to the drug.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
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.
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.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
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.
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.
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)
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.
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
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.
A cell line derived from cultured tumor cells.
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.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Elements of limited time intervals, contributing to particular results or situations.
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.
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.
Benzo-indoles similar to CARBOLINES which are pyrido-indoles. In plants, carbazoles are derived from indole and form some of the INDOLE ALKALOIDS.
Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.
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.
The phosphoric acid ester of serine.
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.
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
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)
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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.
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.
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.
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.
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.
Transport proteins that carry specific substances in the blood or across cell membranes.
An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.
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.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
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.
A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
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.
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).
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.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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)
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.
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 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.
A mitogen-activated protein kinase kinase with specificity for P38 MITOGEN-ACTIVATED PROTEIN KINASES.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
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.
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.
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.
Four carbon unsaturated hydrocarbons containing two double bonds.
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.
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.
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.
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.
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.
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 in which a polyacrylamide gel is used as the diffusion medium.
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.
The sum of the weight of all the atoms in a molecule.
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.
A family of non-receptor, PROLINE-rich protein-tyrosine kinases.
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.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
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.
Compounds or factors that act on a specific enzyme to increase its activity.
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 enzymes
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.
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.
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.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
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.
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.
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.
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.
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.
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)
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.
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.
The phosphoric acid ester of threonine. Used as an identifier in the analysis of peptides, proteins, and enzymes.
A 110-kDa extracellular signal-regulated MAP kinase that is activated in response to cellular stress and by GROWTH FACTOR RECEPTORS-mediated pathways.
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.
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).
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.
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.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
An enzyme that catalyzes the conversion of ATP and PHOSPHORYLASE B to ADP and PHOSPHORYLASE A.
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.
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 KINASES
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
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.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.
Glycoproteins with a wide distribution on hematopoietic and non-hematopoietic cells and strongly expressed on macrophages. CD58 mediates cell adhesion by binding to CD2; (ANTIGENS, CD2); and this enhances antigen-specific T-cell activation.
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.
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.
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.
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.
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.
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.
Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.
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.
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.
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.
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.
Nucleotides in which the purine or pyrimidine base is combined with ribose. (Dorland, 28th ed)

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)

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.
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.
Thyroid hormones can modify cardiac metabolism via multiple molecular mechanisms, yet their integrated effect on overall substrate metabolism is poorly understood. Here we determined the effect of hyperthyroidism on substrate metabolism in the isolated, perfused, contracting rat heart. Male Wistar rats were injected for 7 d with T(3) (0.2 mg/kg x d ip). Plasma free fatty acids increased by 97%, heart weights increased by 33%, and cardiac rate pressure product, an indicator of contractile function, increased by 33% in hyperthyroid rats. Insulin-stimulated glycolytic rates and lactate efflux rates were increased by 33% in hyperthyroid rat hearts, mediated by an increased insulin-stimulated translocation of the glucose transporter GLUT4 to the sarcolemma. This was accompanied by a 70% increase in phosphorylated AMP-activated protein kinase (AMPK) and a 100% increase in phosphorylated acetyl CoA carboxylase, confirming downstream signaling from AMPK. Fatty acid oxidation rates increased in direct proportion
Hu K, Gong X, Ai Q et al.. Department of Pathophysiology, Chongqing Medical University, Chongqing, China.. Cell death & disease. Mar 2017.. The energy sensor AMP-activated protein kinase (AMPK) is crucial for energy homeostasis. Recent studies have revealed that AMPK is involved in various energy-intensive pathological processes such as inflammation and apoptosis. The physiological functions of hepatic AMPK have been well studied, but the pathological significance of AMPK in liver disorders remains largely unknown. In the present study, the phosphorylation status and the roles of AMPK were investigated in mice with lipopolysaccharide (LPS)/d-galactosamine (D-Gal)-induced fulminant hepatitis. The experimental data indicated that the phosphorylation of hepatic AMPK increased in mice with LPS/D-Gal-induced fulminant hepatitis. Pretreatment with the AMPK inhibitor compound C enhanced the early production of pro-inflammatory cytokines but suppressed the late activation of the caspase cascade, reduced ...
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.. ...
TY - JOUR. T1 - Inhibition of AMP-activated protein kinase at the allosteric drug-binding site promotes islet insulin release. AU - Scott, John W. AU - Galic, Sandra. AU - Graham, Kate L. AU - Foitzik, Richard. AU - Ling, Naomi X Y. AU - Dite, Toby A. AU - Issa, Samah M A. AU - Langendorf, Chris G. AU - Weng, Qing Ping. AU - Thomas, Helen E. AU - Kay, Thomas W. AU - Birnberg, Neal C. AU - Steinberg, Gregory R. AU - Kemp, Bruce E. AU - Oakhill, Jonathan S. PY - 2015. Y1 - 2015. N2 - 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 ...
Anterograde transport of late endosomes or lysosomes (LE/Lys) is crucial for proper axon growth. However, the role of energetic nutrients has been poorly explored. Malonyl-CoA is a precursor of fatty acids, and its intracellular levels highly fluctuate depending on glucose availability or the energy sensor AMP-activated protein kinase (AMPK). We demonstrate in HeLa cells that carnitine palmitoyltransferase 1C (CPT1C) senses malonyl-CoA and enhances LE/Lys anterograde transport by interacting with the endoplasmic reticulum protein protrudin and facilitating the transfer of Kinesin-1 from protrudin to LE/Lys. In cultured mouse cortical neurons, glucose deprivation, pharmacological activation of AMPK or inhibition of malonyl-CoA synthesis decreases LE/Lys abundance at the axon terminal, and shortens axon length in a CPT1C-dependent manner. These results identify CPT1C as a new regulator of anterograde LE/Lys transport in response to malonyl-CoA changes, and give insight into how axon growth is ...
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 ...
deletion increased oxidative respiration, enhanced spare respiratory capacity, and induced an M2 macrophage polarization-associated gene profile. Furthermore, miR-33-mediated M2 polarization required miR-33 targeting of the energy sensor AMP-activated protein kinase (AMPK), but not cholesterol efflux. Notably, miR-33 inhibition increased macrophage expression of the retinoic acid-producing enzyme aldehyde dehydrogenase family 1, subfamily A2 (ALDH1A2) and retinal dehydrogenase activity both in vitro and in a mouse model. Consistent with the ability of retinoic acid to foster inducible Tregs, miR-33-depleted macrophages had an enhanced capacity to induce forkhead box P3 (FOXP3) expression in naive CD4+ T cells. Finally, treatment of hypercholesterolemic mice with miR-33 inhibitors for 8 weeks resulted in accumulation of inflammation-suppressing M2 macrophages and FOXP3+ Tregs in plaques and reduced atherosclerosis progression. Collectively, these results reveal that miR-33 regulates macrophage ...
AMP-activated protein kinase (AMPK) is a master metabolic regulator that responds to the AMP: ATP ratio and promotes ATP production when the cell is low on energy. There are two isoforms of the catalytic alpha subunit, AMPKα1 and AMPKα2. Here, we describe the production of a small interfering RNA (siRNA) and a short hairpin RNA (shRNA) targeting both catalytic isoforms of AMPK in human, mouse, and rat. Multiple loop sequences were tested to generate the most effective shRNA. The shRNA causes significant knockdown of both isoforms of AMPKα in mouse and human cells. The shRNA effectively knocked down AMPKα1 and AMPKα2 protein levels, compared to a five basepair mismatch-control shRNA in mouse fibroblast NIH3T3 cells and significantly knocked down AMPKα1 (63%) and AMPKα2 (72%) levels compared to control in human embryonic kidney cells, HEK293s. The shRNA also causes a significant reduction in AMPK activity, measured as phosphorylation of acetyl-CoA carboxylase (ACC), a direct phosphorylation target.
Mitochondrial DNA (mtDNA) deletions occur sporadically in zygotic and somatic tissues and reach their highest concentration in substantia nigra. Previously, we noted the increase of the adenosine monophosphate (AMP)-activated protein kinase (AMPK) transcript by microarray in multiple cells and tissues bearing deletions. In this work, we demonstrate that the induction of AMPK transcript is dependent on deletions by quantitative polymerase chain reaction, and also demonstrate a deficiency in adenosine triphosphate (ATP) synthesis in the same cells. Consistent with AMPK induction, its known targets SREBF1 (sterol regulatory element binding protein-1) and ATG12 were inhibited and induced, respectively. AMPK induction is known to decrease secretory processes in some cells, and the secretion of both osteoprotegerin (OPG) and fibronectin (FN) proteins to the extracellular space was significantly deficient. Deletions caused a defect in the adenosine diphosphate (ADP)-ribosylation factor-like 2 (ARL2) ...
D942 compound: a furancarboxylic acid derivative, which increases glucose uptake in L6 myocytes through AMP-activated protein kinase (AMPK) activation
Chronic exposure to glucocorticoid hormones, resulting from either drug treatment or Cushings syndrome, results in insulin resistance, central obesity, and symptoms similar to the metabolic syndrome. We hypothesized that the major metabolic effects of corticosteroids are mediated by changes in the key metabolic enzyme adenosine monophosphate-activated protein kinase (AMPK) activity. Activation of AMPK is known to stimulate appetite in the hypothalamus and stimulate catabolic processes in the periphery. We assessed AMPK activity and the expression of several metabolic enzymes in the hypothalamus, liver, adipose tissue, and heart of a rat glucocorticoid-excess model as well as in in vitro studies using primary human adipose and primary rat hypothalamic cell cultures, and a human hepatoma cell line treated with dexamethasone and metformin. Glucocorticoid treatment inhibited AMPK activity in rat adipose tissue and heart, while stimulating it in the liver and hypothalamus. Similar data were observed ...
Human 5-AMP-activated protein kinase catalytic subunit alpha-2 (PRKAA2) ELISA Kit can measure Human 5-AMP-activated protein kinase catalytic subunit alpha-2 in serum, blood, plasma, cell culture supernatant and other related supernatants and tissues.
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 ...
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 ...
Brown (BAT) and white (WAT) adipose tissues are significant contributors to whole-body energy homeostasis. A disturbance in their metabolic function could result in the development of obesity and subsequent metabolic complications. The energy-sensing enzyme of the cell, AMP-activated protein kinase (AMPK), has been vastly studied in skeletal muscle and liver, but its role in BAT and WAT metabolism is elusive. We generated an inducible, adipocyte-specific knockout mouse model for the two AMPK β subunits (iβ1β2AKO) and found that iβ1β2AKO mice were intolerant to cold, and resistant to β3-adrenergic activation of BAT and browning of WAT. These defects in BAT activity were not due to the AMPK-ACC axis, but instead were due to compromised integrity of mitochondria. Mitochondrial morphology, function, and autophagy were all distorted in iβ1β2AKO mice, measured via transmission electron microscopy (TEM), respiration, and immunoblotting, respectively. These findings provide strong evidence that ...
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 ...
AMP-activated protein kinase connects cellular energy metabolism to KATP channel function. J Mol Cell Cardiol. 2012 Feb; 52(2):410-8 ...
TY - JOUR. T1 - Structural Insight into AMPK Regulation. T2 - ADP Comes into Play. AU - Jin, Xiangshu. AU - Townley, Robert. AU - Shapiro, Lawrence. PY - 2007/10/16. Y1 - 2007/10/16. N2 - The AMP-activated protein kinase (AMPK), a sensor of cellular energy status found in all eukaryotes, responds to changes in intracellular adenosine nucleotide levels resulting from metabolic stresses. Here we describe crystal structures of a heterotrimeric regulatory core fragment from Schizosaccharomyces pombe AMPK in complex with ADP, ADP/AMP, ADP/ATP, and 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranotide (AICAR phosphate, or ZMP), a well-characterized AMPK activator. Prior crystallographic studies had revealed a single site in the γ subunit that binds either ATP or AMP within Bateman domain B. Here we show that ZMP binds at this site, mimicking the binding of AMP. An analogous site in Bateman domain A selectively accommodates ADP, which binds in a distinct manner that also involves direct ligation to ...
TY - JOUR. T1 - Regulation of adenosine 5,monophosphate-activated protein kinase and lipogenesis by androgens contributes to visceral obesity in an estrogen-deficient state. AU - McInnes, Kerry. AU - Corbould, Anne Margaret. AU - Simpson, Evan R. AU - Jones, Margaret E. PY - 2006. Y1 - 2006. UR - http://www.scopus.com/record/display.url?eid=2-s2.0-33751517959&origin=resultslist&sort=plf-f&src=s&st1=protein+kinase+and+lipogenesis+by+androgens+co. U2 - 10.1210/en.2006-0879. DO - 10.1210/en.2006-0879. M3 - Article. VL - 147. SP - 5907. EP - 5913. JO - Endocrinology. JF - Endocrinology. SN - 0013-7227. IS - 12. ER - ...
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, ...
The AMP-activated protein kinase (AMPK) is an evolutionarily conserved sensor of cellular energy status, and recent data demonstrate that it also plays a critical role in systemic energy balance. AMPK integrates nutritional and hormonal signals in peripheral tissues and the hypothalamus. It mediates …
The heterotetrameric K+-channel KCNQ1/KCNE1 is expressed in heart, skeletal muscle, liver and several epithelia including the renal proximal tubule. In the heart, it contributes to the repolarization of cardiomyocytes. The repolarization is impaired in ischemia. Ischemia stimulates the AMP-activated protein kinase (AMPK), a serine/threonine kinase, sensing energy depletion and stimulating several cellular mechanisms to enhance energy production and to limit energy utilization. AMPK has previously been shown to downregulate the epithelial Na+ channel ENaC, an effect mediated by the ubiquitin ligase Nedd4-2. The present study explored whether AMPK regulates KCNQ1/KCNE1. To this end, cRNA encoding KCNQ1/KCNE1 was injected into Xenopus oocytes with and without additional injection of wild type AMPK (AMPKα1 + AMPKβ1 + AMPKγ1), of the constitutively active γR70QAMPK (α1β1γ1(R70Q)), of the kinase dead mutant αK45RAMPK (α1(K45R)β1γ1), or of the ubiquitin ligase Nedd4-2. KCNQ1/KCNE1 activity ...
The AMP-activated protein kinase (AMPK) is a member of a metabolite-sensing protein kinase family that is found in all eukaryotes. AMPK activity is regulated by vigorous exercise, nutrient starvation and ischemia/hypoxia, and modulates many aspects of mammalian cell metabolism. The AMPK yeast homolo …
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 ...
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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Dive into the research topics of Evidence for LKB1/AMP-activated protein kinase/endothelial nitric oxide synthase cascade regulated by hepatocyte growth factor, S-adenosylmethionine, and nitric oxide in hepatocyte proliferation. Together they form a unique fingerprint. ...
Connexios Life Sciences and Boehringer Ingelheim are collaborating on the development of AMP-activated protein kinase (AMPK) stimulants for the treatment of
AMP-activated protein kinase signaling protects oligodendrocytes that restore central nervous system functions in an experimental autoimmune encephalomyelitis model
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, ...
AMP-activated protein kinase (AMPK) is highly conserved from yeast to plants and animals and plays a key role in the regulation of energy homeostasis (1). AMPK is a heterotrimeric complex composed of a catalytic α subunit and regulatory β and γ subunits, each of which is encoded by two or three distinct genes (α1, 2; β1, 2; γ1, 2, 3) (2). The kinase is activated by an elevated AMP/ATP ratio due to cellular and environmental stress, such as heat shock, hypoxia, and ischemia (1). The tumor suppressor LKB1, in association with accessory proteins STRAD and MO25, phosphorylates AMPKα at Thr172 in the activation loop, and this phosphorylation is required for AMPK activation (3-5). AMPK phosphorylates a number of targets controlling cellular processes such as metabolism, cell growth, and autophagy (6). It suppresses the activity of the mammalian target of rapamycin (mTOR), that plays a key role in promoting cell growth. The regulatory associated protein of mTOR (Raptor) was identified as an mTOR ...
The protein kinase AMPK (adenosine monophosphate-activated protein kinase) directly monitors cellular energy stores as reflected by changes in cellular concentrations of AMP, adenosine diphosphate (ADP), and adenosine triphosphate (ATP). Through phosphorylation of its targets, it helps to control metabolism, polarity, autophagy, and the restraint of cell proliferation. Activation of AMPK is also proposed to be beneficial for the treatment of diseases, including cancer and diabetes. Hawley et al. (see the Perspective by Shaw and Cantley) report that AMPK can be activated by high concentrations of salicylate, a compound derived from the very commonly used drug aspirin. In mice, salicylate promoted fatty acid and carbohydrate metabolism in an AMPK-dependent fashion.. S. A. Hawley, M. D. Fullerton, F. A. Ross, J. D. Schertzer, C. Chevtzoff, K. J. Walker, M. W. Peggie, D. Zibrova, K. A. Green, K. J. Mustard, B. E. Kemp, K. Sakamoto, G. R. Steinberg, D. G. Hardie, The ancient drug salicylate directly ...
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. Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively. Regulates insulin-signaling and glycolysis by phosphorylating ...
Regular exercise can protect the heart against external stimuli, but the mechanism is not well comprehended. sympathetic nervous system and the consequent launch of catecholamines, which stimulate the -adrenergic receptors in the heart, are very important. Isoproterenol (ISO), a nonselective -adrenergic receptor agonist, can robustly induce cardiac fibrosis in animal models. As well, transgenic mice with cardiac overexpressing -adrenergic receptors showed cardiac fibrosis [1]. Exercise teaching offers been shown to reduce fibrosis and matrix metalloproteinase dysregulation in the heart of aged rats [2]. However, the mechanism by which exercise teaching alleviates cardiac redesigning remains elusive. Adenosine monophosphate-activated protein kinase (AMPK) is an evolutionarily conserved serine/threonine protein kinase that is a expert regulator of energy status from your single-cell to whole-body levels [3]. AMPK can be triggered by conditions that increase intracellular AMP such as exercise [4], ...
The adipocyte hypertrophy induced by HFD were attenuated by VPA and ET. HFD decreased 5 AMP-activated protein kinase (AMPK) activity in muscle as well as peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and uncoupling protein 1 (UCP1) proteins in eWAT, while not affecting circulating irisin.. VPA increased eWAT Tmem26 mRNA levels in the standard diet-fed group, whereas ET increased AMPK, interleukin 6 (IL-6) and fibronectin type III domain-containing protein 5 (FNDC5) protein expression in muscle, but had no impact on circulating irisin protein content.. In eWAT, ET increased bone morphogenetic protein 7 (Bmp7), Cidea and PGC-1α in both diet-fed animals, whereas BMP7, Prdm16, UCP1 and FNDC5 only in standard diet-fed group.. SIGNIFICANCE: ...
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 ...
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 ...
TY - JOUR. T1 - Malonyl-CoA decarboxylase is not a substrate of AMP-activated protein kinase in rat fast-twitch skeletal muscle or an islet cell line. AU - Habinowski, Susan A.. AU - Hirshman, Michael. AU - Sakamoto, Kei. AU - Kemp, Bruce E.. AU - Gould, Stephen J.. AU - Goodyear, Laurie J.. AU - Witters, Lee A.. N1 - Funding Information: The authors thank Christopher Newgard (Southwestern) for the gift of the 832/13 cell line. This work was supported by an NIH grant (DK35712) awarded to L.A.W. and a grant from the American Diabetes Association to L.J.G. and L.A.W. B.E.K. is a NHMRC Australia Fellow. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.. PY - 2001/12/1. Y1 - 2001/12/1. N2 - The AMP-activated protein kinase (AMPK) plays an important role in fuel metabolism in exercising skeletal muscle and possibly in the islet cell with respect to insulin secretion. Some of these effects are due to AMPK-mediated regulation of cellular malonyl-CoA content, ascribed to the ability of AMPK ...
TY - JOUR. T1 - The Caenorhabditis elegans AMP-activated protein kinase AAK-2 is phosphorylated by LKB1 and is required for resistance to oxidative stress and for normal motility and foraging behavior. AU - Lee, Hyojin. AU - Jeong, Soo Cho. AU - Lambacher, Nils. AU - Lee, Jieun. AU - Lee, Se Jin. AU - Tae, Hoon Lee. AU - Gartner, Anton. AU - Koo, Hyeon Sook. PY - 2008/5/30. Y1 - 2008/5/30. N2 - AAK-2 is one of two α isoforms of the AMP-activated protein kinase in Caenorhabditis elegans and is involved in life span maintenance, stress responses, and germ cell cycle arrest upon dauer entry. We found that AAK-2 was phosphorylated at threonine 243 in response to paraquat treatment and that this phosphorylation depends on PAR-4, the C. elegans LKB1 homologue. Both aak-2 mutation and par-4 knockdown increased the sensitivity of C. elegans worms to paraquat, and the double deficiency did not further increase sensitivity, indicating that aak-2 and par-4 act in a linear pathway. Both mutations also ...
TY - JOUR. T1 - AMP-activated protein kinase regulates the expression of human telomerase reverse transcriptase. AU - Jo, Daum. AU - Park, Rackhyun. AU - Kim, Hyunju. AU - Jang, Minsu. AU - Lee, Eun Ju. AU - Jang, Ik Soon. AU - Park, Junsoo. N1 - Publisher Copyright: © 2018 Jo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.. PY - 2018/11. Y1 - 2018/11. N2 - The expression of hTERT in tumor cells contributes to oncogenic transformation by promoting immortalization. For this reason, hTERT is one of the major targets for cancer therapy, and an efficient method to downregulate hTERT expression is required for treatment of hTERT-positive cancer. In this report, we demonstrated that inhibition of AMP-activated protein kinase (AMPK) downregulates the expression of hTERT. We screened cell signaling pathways in ...
Though the hunger-reduction phenomenon reported during ketogenic diets is well-known, the underlying molecular and cellular mechanisms remain uncertain. Ketosis has been demonstrated to exert an anorexigenic effect via cholecystokinin (CCK) release while reducing orexigenic signals e.g., via ghrelin. However, ketone bodies (KB) seem to be able to increase food intake through AMP-activated protein kinase (AMPK) phosphorylation, gamma-aminobutyric acid (GABA) and the release and production of adiponectin. The aim of this review is to provide a summary of our current knowledge of the effects of ketogenic diet (KD) on food control in an effort to unify the apparently contradictory data into a coherent picture.
Rationale: Elevated levels of C/EBP homologous protein (CHOP), a member of the C/EBP transcription factor family, in advanced atherosclerotic plaques is reported to be associated with atherosclerotic plaque rupture in humans. However, the molecular mechanism by which CHOP accumulation occurs is poorly defined. Objective: The aim of this study was to investigate if (1) macrophage AMP-activated kinase (AMPK) regulates cellular CHOP accumulation and (2) whole-body Ampk deletion leads to neointimal disruption. Methods and Results: In isolated or cultured macrophages, Ampkα1 deletion markedly increased apoptosis and CHOP, whereas pharmacological activation of AMPK dramatically reduced CHOP protein level via promoting CHOP degradation by proteasome. In addition, co-transfection of Chop-specific siRNA, but not control siRNA, markedly reduced apoptosis in macrophages transfected with Ampkα1-specific siRNA. Mechanistically, AMPKα1 was found to co-immunoprecipitate with CHOP and phosphorylate CHOP at ...
Alzheimer disease is an age-related neurodegenerative disorder characterized by amyloid-beta (Abeta) peptide deposition into cerebral amyloid plaques. The natural polyphenol resveratrol promotes anti-aging pathways via the activation of several metabolic sensors, including the AMP-activated protein kinase (AMPK). Resveratrol also lowers Abeta levels in cell lines; however, the underlying mechanism responsible for this effect is largely unknown. Moreover, the bioavailability of resveratrol in the brain remains uncertain. Here we show that AMPK signaling controls Abeta metabolism and mediates the anti-amyloidogenic effect of resveratrol in non-neuronal and neuronal cells, including in mouse primary neurons. Resveratrol increased cytosolic calcium levels and promoted AMPK activation by the calcium/calmodulin-dependent protein kinase kinase-beta. Direct pharmacological and genetic activation of AMPK lowered extracellular Abeta accumulation, whereas AMPK inhibition reduced the effect of resveratrol on Abeta
Because polyphenols may have beneficial effects on dyslipidemia, which accelerates atherosclerosis in diabetes, we examined the effect of polyphenols on hepatocellular AMP-activated protein kinase (AMPK) activity and lipid levels, as well as hyperlipidemia and atherogenesis in type 1 diabetic LDL receptor-deficient mice (DMLDLR−/−). In HepG2 hepatocytes, polyphenols, including resveratrol (a major polyphenol in red wine), apigenin, and S17834 (a synthetic polyphenol), increased phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase (ACC), and they increased activity of AMPK with 200 times the potency of metformin. The polyphenols also prevented the lipid accumulation that occurred in HepG2 cells exposed to high glucose, and their ability to do so was mimicked and abrogated, respectively, by overexpression of constitutively active and dominant-negative AMPK mutants. Furthermore, treatment of DMLDLR−/− mice with S17834 prevented the decrease in AMPK and ACC ...
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 ...
Hibernating animals develop fatty liver when active in summertime and undergo a switch to a fat oxidation state in the winter. We hypothesized that this switch might be determined by AMP and the dominance of opposing effects: metabolism through AMP deaminase (AMPD2) (summer) and activation of AMP-activated protein kinase (AMPK) (winter). Liver samples were obtained from 13-lined ground squirrels at different times during the year, including summer and multiples stages of winter hibernation, and fat synthesis and β-fatty acid oxidation were evaluated. Changes in fat metabolism were correlated with changes in AMPD2 activity and intrahepatic uric acid (downstream product of AMPD2), as well as changes in AMPK and intrahepatic β-hydroxybutyrate (a marker of fat oxidation). Hepatic fat accumulation occurred during the summer with relatively increased enzymes associated with fat synthesis (FAS, ACL and ACC) and decreased enoyl CoA hydratase (ECH1) and carnitine palmitoyltransferase 1A (CPT1A), rate limiting
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 ...
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 ...
Chronic fatigue syndrome: Exercise performance related to immune dysfunction. AMP-activated protein kinase: A key system mediating metabolic responses to exercise
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 ...
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 ...
The present study is the first demonstration that administration of AICAR to insulin-resistant HF rats simultaneously increases glucose and FA uptake into skeletal muscle in close association with activation of AMPK. These effects occurred preferentially in white muscle and were consistent with the previously described improvement of insulin sensitivity in white muscle 24 h after AICAR treatment (8). Contrary to our initial speculation, there was no higher FA uptake in red muscle to balance the lack of AICAR effect on glucose uptake in this muscle type.. It is known that fluxes of glucose and FA into muscle are increased from the circulation during exercise (1,23,24). Recent studies have revealed an important role of AMPK in exercise-induced changes in fuel metabolism (1,2). However, many other factors are also important metabolic regulators in contracting muscle (7), such as decreased energy storage (ATP and creatine phosphate content) (25), increases in metabolic rate, muscle blood flow, and ...
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 ...
Background: The yeast SNF1 protein kinase and the mammalian AMP-activated protein kinase are highly conserved heterotrimeric complexes that are metabolic master switches involved in the switch from fermentative/anaerobic to oxidative metabolism. They are activated by cellular stresses that deplete cellular ATP, and SNF1 is essential in the response to glucose starvation. In both cases, activation requires phosphorylation at a conserved threonine residue within the activation loop of the kinase domain, but identifying the upstream kinase(s) responsible for this has been a challenging, unsolved problem. Results: Using a library of strains that express 119 yeast protein kinases as GST fusions, we identified Elm1p as the sole kinase that could activate the kinase domain of AMP-activated protein kinase in vitro. Elm1p also activated the purified SNF1 complex, and this correlated with phosphorylation of Thr210 in the activation loop. Removal of the C-terminal domain increased the Elm1p kinase ...
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 ...
Metformin is a biguanide antihyperglycemic that is approved for the management of type 2 diabetes mellitus. The mechanism by which metformin enhance insulin sensitivity are not fully characterized. At a molecular level, metformin may increase the activity of the enzyme adenosine monophosphate-activated protein kinase Metformin appears to suppress hepatic glucose output, decreased intestinal absorption of glucose, increased insulin mediated glucose utilization in peripheral tissues and has an antilypolytic affect on fatty acid concentration reducing gluconeogenesis . It does not produce hypoglycemia in either normal subjects or patients with type 2 diabetes. It is rapidly absorbed from the small intestine and without metabolism largely excreted in the urine. It is available in a generic form as 500 mg, 850mg and 1000 mg tablets. The target dose of metformin is in the range of 1500 mg to 2550mg . Metformin is given with meals to reduce the gastrointestinal side-effects. The most common ...
Ghrelin is a stomach-derived peptide that increases food intake through the activation of hypothalamic AMP-activated protein kinase (AMPK). However, the molecular mechanisms initiated by the activation of the ghrelin receptor, which in turn lead to A
5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) is an established pharmacological activator of AMP-activated protein kinase (AMPK). Both, AICAR and AMPK were reported to attenuate inflammation. However, AICAR is known for many AMPK-independent effects, although the mechanisms remain incompletely understood. Here we report a potent suppression of lipopolysaccharide (LPS)-induced inflammatory gene expression by AICAR in primary human macrophages, which occurred independently of its conversion to AMPK-activating 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranosyl monophosphate. Although AICAR did not interfere with activation of cytosolic signalling cascades and nuclear translocation of nuclear factor - κB (NFκB) by LPS, it prevented the recruitment of NFκB and RNA polymerase II to target gene promoters. AICAR also inhibited signal transducer and activator of transcription 3 (STAT3)-dependent induction of interleukin (IL) IL-6 and IL-10 targets, while leaving STAT6 and HIF1α-dependent gene
Dive into the research topics of AMP-activated protein kinase activators can inhibit the growth of prostate cancer cells by multiple mechanisms. Together they form a unique fingerprint. ...
in Journal of Biological Chemistry (2011), 286(19), 16879-90. Extracellular Ca(2+) is essential for the development of stable epithelial tight junctions. We find that in the absence of extracellular Ca(2+), AMP-activated protein kinase (AMPK) activation and glycogen ... [more ▼]. Extracellular Ca(2+) is essential for the development of stable epithelial tight junctions. We find that in the absence of extracellular Ca(2+), AMP-activated protein kinase (AMPK) activation and glycogen synthase kinase (GSK)-3beta inhibition independently induce the localization of epithelial tight junction components to the plasma membrane. The Ca(2+)-independent deposition of junctional proteins induced by AMPK activation and GSK-3beta inhibition is independent of E-cadherin. Furthermore, the nectin-afadin system is required for the deposition of tight junction components induced by AMPK activation, but it is not required for that induced by GSK-3beta inhibition. Phosphorylation studies demonstrate that afadin is ...
The serine/threonine kinase LKB1 is a tumor suppressor gene mutated in the familial cancer condition Peutz-Jeghers syndrome (PJS), as well as in 30% of sporadic non-small cell lung cancer (NSCLC). One of the critical substrates of LKB1 is the AMP-activated protein kinase (AMPK). AMPK is a highly conserved sensor of cellular energy status found in all eukaryotic cells that restores metabolic homeostasis following stress. Thus LKB1 is a unique energy-state sensitive regulator of growth and metabolic reprogramming via its effects on AMPK. Our laboratory has performed a three-pronged screen to identify novel substrates of AMPK that may mediate its effects on metabolism and growth control. These studies have led to the identification of components of the mTOR signaling pathway (raptor, TSC2), the autophagy pathway (ULK1), and transcriptional regulators of metabolism (Srebp1, HDAC4/5/7) all as direct substrates of AMPK. Collectively, these studies uncovered novel conserved effectors of LKB1 and AMPK ...
THE BCA2 & AMPK PARADIGM: UNRAVELING THE CANCER CONNECTION By DANIELA (BUAC) VENTRO December 2013 Advisor: Dr. Q Ping Dou and Angelika M. Burger (deceased) Major: Cancer Biology Degree: Doctor of Philosophy Adenosine monophosphate-activated kinase (AMPK), a master regulator of cellular energy homeostasis, has emerged as a promising molecular target in the prevention of breast cancer, and phase II and III clinical trials using the FDA-approved, AMPK activating, anti-diabetic drug metformin are promising in this regard, but the question of why metformin is protective for some women but not others still remains. Breast Cancer Associated Gene 2 (BCA2/Rabring7/RNF115), a novel RING-finger ubiquitin E3 ligase, is overexpressed in |50% of breast tumors. Herein, I hypothesized that BCA2 is an endogenous inhibitor of AMPK activation in breast cancer cells and that BCA2 inhibition would therefore increase the efficacy of metformin. My hypothesis is strongly supported by the finding that BCA2 overexpression
From NCBI 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. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2013]. From UniProt: ...
Objective: To investigate the effect of lateral ventricle injection inhibitor nesfatin-1 on glycolipid metabolism and its relationship with hypothalamic AMPK expression. Methods: Nesfatin-1 was injected into the lateral ventricle of the rat by the brain stereotactic technique (nesfatin-1 group), and the sham operation group was injected with an equal volume of artificial cerebrospinal fluid and the control group had no interference factor. The rats were kept for 4 weeks and an automatic biochemical analyzer was used to detect blood sugar and blood lipid levels. The expression of AMPK mRNA in rat hypothalamus was detected by RT-PCR. The expression of AMPKα and phosphorylated AMPKα (pAMPKα) in the rat hypothalamus was detected by Western blot. Results: (1)According to the results of biochemical tests, compared to the control group, the level of FPG and TG in experimental group were significantly decreased (P ...
This AMPK (A1/B2/G2) recombinant human protein (full length) was expressed in insect cells. AMPK (A1/B2/G2) serine/threonine kinase or AMP-activated protein kinase (AMPK) exhibits a key role as a master regulator of cellular energy homeostasis. AMPK exists as a heterotrimeric complex composed of a c
Statins are known to modulate cell surface cholesterol (CSC) and AMP-activated protein kinase (AMPK) in nonneural cells; however no study demonstrates whether CSC and AMPK may regulate simvastatin induced neuritogenesis (SIN). We found that simvastatin (SIM) maintains CSC as shown by Fillipin III staining, Flotillin-2 protein expression / localization and phosphorylation of various receptor tyrosine kinases (RTKs) in the plasma membrane. Modulation of CSC revealed that SIN is critically dependent on this CSC. Simultaneously, phospho array for mitogen activated protein kinases (MAPKs) revealed PI3K / Akt as intracellular pathway which modulates lipid pathway by inhibiting AMPK activation. Though, SIM led to a transient increase in AMPK phosphorylation followed by a sudden decline; the effect was independent of PI3K. Strikingly, AMPK phosphorylation was regulated by protein phosphatase 2A (PP2A) activity which was enhanced upon SIM treatment as evidenced by increase in threonine phosphorylation. ...
Results HD feeding plus low-dose STZ injection successfully induced T2DM. Compared to normal control, diabetic mice manifested higher fasting-blood glucose level, lower glucose tolerance in OGTT examination (n=12, p,0.05), but there was no difference in plasma insulin levels. RSV alleviated MI/R injury in both normal and diabetic mice, as evidenced by decreased infarct size, cardiomyocytes apoptosis, caspase-3 activity, improved cardiac function (n=10, all p,0.05). Moreover, RSV treatment improved APN level, upregulated APN multimerisation both in plasma and adipose tissue, and increased DsbA-L expression in adipose tissue in diabetic mice (all p,0.01). Conversely, administration of AMPK inhibitor Compound C significantly attenuated the cardioprotective effects of RSV (all p,0.05).. ...
Prkaa2 - Prkaa2 (GFP-tagged) - Mouse protein kinase AMP-activated alpha 2 catalytic subunit (Prkaa2), (10ug) available for purchase from OriGene - Your Gene Company.
All living cells require energy, usually provided in the form of ATP, to carry out fundamental processes like movement and growth. Therefore, cells have to balance energy supply with the demand. AMP-activated protein kinase (AMPK) has emerged as a central component of a signalling pathway involved in regulating intracellular energy homeostasis. When ADP and AMP levels increase, concomitant with a fall in ATP levels, AMPK is activated by phosphorylation on threonine-172 within the catalytic a subunit by upstream kinases including LKB1 and calcium/calmodulin protein kinase kinase (CaMKK) ß. Once activated, AMPK responds by phosphorylating downstream targets, the net effect of which is to switch off ATP-consuming processes and switch on ATP-producing processes. When the levels of nucleotides are restored to normal physiological concentrations, AMPK is inactivated by an unknown protein phosphatase(s). Major advances have been made over the last five years in understanding the molecular mechanism of how
Cyclic adenosine monophosphate (cAMP, cyclic AMP, or 3,5-cyclic adenosine monophosphate) is a second messenger important in many biological processes. cAMP is a derivative of adenosine triphosphate (ATP) and used for intracellular signal transduction in many different organisms, conveying the cAMP-dependent pathway. It should not be confused with 5-AMP-activated protein kinase (AMP-activated protein kinase ...
Objective: To investigate the effect and mechanism of CTRP13 on hepatic sinusoidal capillarization induced by high glucose in rat liver sinusoidal endothelial cells (rLSECs).Results: CTRP13 was reduced in high glucose-treated rLSECs. High glucose increased LN and CAV-1 expression and inhibited CaMKKβ and AMPK phosphorylation. CTRP13 overexpression protected rLSECs against high glucose-induced increase of LN and CAV-1 expression. Moreover, CTRP13 overexpression increased high glucose-induced inhibition of CaMKKβ and AMPK activation in CTRP13-overexpressing rLSECs. Inhibition of CaMKKβ and AMPK disturbed the protective effects of CTRP13 in high glucose-induced increase of LN and CAV-1. Hepatic steatosis was enhanced and basement membrane was thickened in liver of diabetic fatty liver rats.Conclusions: Our data identified the protective role of CTRP13 in hepatic sinusoidal capillarization induced by high glucose via activating CAMKKβ/AMPK pathway. CTRP13 may be a potential target
PubMed journal article Cinnamon extract enhances glucose uptake in 3T3-L1 adipocytes and C2C12 myocytes by inducing LKB1-AMP-activated protein kinase signaling were found in PRIME PubMed. Download Prime PubMed App to iPhone, iPad, or Android
Author(s): Mo, Jung-Soon; Meng, Zhipeng; Kim, Young Chul; Park, Hyun Woo; Hansen, Carsten Gram; Kim, Soohyun; Lim, Dae-Sik; Guan, Kun-Liang | Abstract: YAP (Yes-associated protein) is a transcription co-activator in the Hippo tumour suppressor pathway and controls cell growth, tissue homeostasis and organ size. YAP is inhibited by the kinase Lats, which phosphorylates YAP to induce its cytoplasmic localization and proteasomal degradation. YAP induces gene expression by binding to the TEAD family transcription factors. Dysregulation of the Hippo-YAP pathway is frequently observed in human cancers. Here we show that cellular energy stress induces YAP phosphorylation, in part due to AMPK-dependent Lats activation, thereby inhibiting YAP activity. Moreover, AMPK directly phosphorylates YAP Ser 94, a residue essential for the interaction with TEAD, thus disrupting the YAP-TEAD interaction. AMPK-induced YAP inhibition can suppress oncogenic transformation of Lats-null cells with high YAP activity. Our study
HIGHLIGHTS: AMPK-dependent Raptor Ser792 phosphorylation does not influence mTORC1-S6K1 activation by intense muscle contraction. α2 -AMPK activity-deficient mice have lower contraction-stimulated protein synthesis Increasing glycogen activates mTORC1-S6K1 independently of AMPK α2 Normalizing muscle glycogen content rescues reduced protein synthesis in AMPK-deficient mice ABSTRACT: Objective The mammalian Target of Rapamycin Complex 1 (mTORC1)-S6K1 signalling pathway regulates muscle growth-related protein synthesis and is antagonized by AMP-activated protein kinase (AMPK) in multiple cell types. Resistance exercise stimulates skeletal muscle mTORC1-S6K1 and AMPK signalling and post-contraction protein synthesis. Glycogen inhibits AMPK and has been proposed as a pro-anabolic stimulus. The aim of this study was to investigate how muscle mTORC1-S6K1 signalling and protein synthesis respond to resistance exercise-mimicking contraction in the absence of AMPK and with glycogen-manipulation. Methods ...
Metabolix™ AMPK is an orthomolecular combination of ingredients that together contribute to AMPK activation with beneficial effects in Metabolic Syndrome.. Metabolic syndrome (MetS) is a cluster of health problems created by insulin resistance (IR) which include: fat accumulation (especially around the waist), high blood pressure, high triglycerides (blood lipids level), high blood sugar, and low good cholesterol (HDL). Together, they result in accelerated aging and an increased risk of coronary artery disease events such as heart attack, stroke, and diabetes. The good news is that apart from diet and exercise, scientific research has recently discovered that the enzyme 5′-AMP-activated protein kinase (AMPK) has a major role in the regulation of cellular lipid and protein metabolism. AMPK regulates glucose transport, lipid and protein synthesis, and fuel metabolism as well as other factors that have been linked to insulin resistance.. ...
5'-AMP-activated protein kinase subunit gamma-1 is an enzyme that in humans is encoded by the PRKAG1 gene. The protein encoded ... "Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding". The Biochemical Journal ... "Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding". The Biochemical Journal ... "An activating mutation in the gamma1 subunit of the AMP-activated protein kinase". FEBS Letters. 500 (3): 163-8. doi:10.1016/ ...
AMP-activated protein kinase. • PGC‐1α: peroxisome proliferator-activated receptor gamma coactivator-1α. • S6K1: p70S6 kinase. ... thereby triggering the activation of AMP-activated protein kinase (AMPK) which subsequently phosphorylates peroxisome ... the p70S6 kinase and the translation repressor protein 4EBP1).[94][96] The suppression of muscle protein breakdown following ... and inhibiting muscle protein breakdown (MPB).[94][95] The stimulation of muscle protein synthesis by resistance training ...
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 ...
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, ...
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. ...
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): 918-22. Bibcode:2012Sci... ... Acetylation of cellular proteins is a well-established phenomenon in the regulation of protein function at the post- ... Protein binding. 80-90%[1]. Metabolism. Liver, (CYP2C19 and possibly CYP3A), some is also hydrolysed to salicylate in the gut ...
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 ...
A specific method for activating AMP-activated protein kinase in intact cells?". European Journal of Biochemistry. 229 (2): 558 ... 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 ...
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 ...
Nutrient sensors of the mammalian species, in particular AMP-activated protein kinase (AMPK). AMPK has been suggested as a ... Clock genes are transcribed and translated into a protein product, and this protein accumulates and inhibits the promoter of ... Another nutrient sensor in cAMP-response element (CRE) binding protein (CREB) also play a role and may be involved as part of ... RGS16, a gene regulating G-protein coupled receptor signaling, attenuates FAA but is also not necessary for it. Up until the ...
PPARδ-AMP-activated protein kinase (AMPK) axis agonists (e.g. AICAR) are also banned. Meldonium was banned on 1 January 2016, ... Glucocorticoids are a class of corticosteroids that affect the metabolism of carbohydrates, fat, and proteins, and regulate ... 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), ...
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 (7): 1635-1640. ...
"Metformin and phenformin activate AMP-activated protein kinase in the heart by increasing cytosolic AMP concentration". ... March 2016). "HL156A, a novel AMP-activated protein kinase activator, is protective against peritoneal fibrosis in an in vivo ... October 2001). "Role of AMP-activated protein kinase in mechanism of metformin action". The Journal of Clinical Investigation. ... July 2002). "Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes". ...
In 2012, salicylic acid was found to activate AMP-activated protein kinase, which has been suggested as a possible explanation ... May 2012). "The ancient drug salicylate directly activates AMP-activated protein kinase". Science. 336 (6083): 918-22. Bibcode: ... 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; ...
... two molecules of cyclic AMP bind to the regulatory subunit of protein kinase A, which activates it allowing the catalytic ... This latter enzyme is itself activated by protein kinase A and deactivated by phosphoprotein phosphatase-1. Protein kinase A ... Epinephrine binds to a receptor protein that activates adenylate cyclase. The latter enzyme causes the formation of cyclic AMP ... The calcium ions activate phosphorylase kinase. This activates glycogen phosphorylase and inhibits glycogen synthase. ...
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 ...
AMP-activated protein kinase,. (3-metil-2-oksobutanoat dehidrogenaza (prenos acetila)) (EC 2.7.11.4) ... Protein kinaza C (EC 2.7.11.13). Protein kinaza C, Protein kinaza Cζ, PKC alfa, PRKCB1, PRKCD, PRKCE, PRKCH, PRKCG, PRKCI, ... Eric J. Toone (2006). Advances in Enzymology and Related Areas of Molecular Biology, Protein Evolution (Volume 75 изд.). Wiley- ... Receptor protein serin/treonin kinaza (EC 2.7.11.30). Koštani morfogenetski proteinski receptori (BMPR1, BMPR1A, BMPR1B, BMPR2 ...
AMP-activated protein kinase,. (3-metil-2-oksobutanoat dehidrogenaza (prenos acetila)) (EC 2.7.11.4). BCKDK, BCKDHA, BCKDHB ... Protein kinaza C (EC 2.7.11.13). Protein kinaza C, Protein kinaza Cζ, PKC alfa, PRKCB1, PRKCD, PRKCE, PRKCH, PRKCG, PRKCI, ... Eric J. Toone (2006). Advances in Enzymology and Related Areas of Molecular Biology, Protein Evolution (Volume 75 изд.). Wiley- ... Nicholas C. Price; Lewis Stevens (1999). Fundamentals of Enzymology: The Cell and Molecular Biology of Catalytic Proteins ( ...
AMPKα1 (PRKAA1; protein kinase, AMP-activated, alpha 1 catalytic subunit). *AMPKα2 (protein kinase, AMP-activated, alpha 2 ... The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent ... The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress ... LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. „Curr Biol". Nov 11;13. 22, s. 2004-8, 2003. PMID: ...
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, ...
"Noveld-Xylose Derivatives Stimulate Muscle Glucose Uptake by Activating AMP-Activated Protein Kinase α". Journal of Medicinal ... Increases the Rate of Glucose Uptake in L6 Myotubes and Augments Insulin Secretion from Pancreatic Beta-Cells by Activating ...
... 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 AMP-activated protein kinase, which responds to an increase in AMP ... Hardie DG, Scott JW, Pan DA, Hudson ER (July 2003). "Management of cellular energy by the AMP-activated protein kinase system ... Hardie DG (February 1992). "Regulation of fatty acid and cholesterol metabolism by the AMP-activated protein kinase". ...
"Pharmacological inhibition of AMP-activated protein kinase provides neuroprotection in stroke". J. Biol. Chem. 280 (21): 20493- ...
"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 ...
Cyclic AMP activates protein kinase A. Protein kinase A phosphorylates and partially activates phosphorylase kinase. Adrenaline ... Calcium ions bind to calmodulin, which leads to further activation of phosphorylase kinase. Phosphorylase kinase phosphorylates ... This trimeric G protein dissociates to Gs alpha and Gs beta/gamma subunits. Gs alpha stimulates adenylyl cyclase, thus ... Adrenaline binds to β2 receptors on liver cells, which changes conformation and helps Gs, a heterotrimeric G protein, exchange ...
Jibb, LA; Richards, JG (2008). "AMP-activated protein kinase activity during metabolic rate depression in the hypoxic goldfish ... 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 ...
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 ...
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): 860-7. ... Vega RB, Harrison BC, Meadows E, Roberts CR, Papst PJ, Olson EN, McKinsey TA (October 2004). "Protein kinases C and D mediate ... "Activation of the myocyte enhancer factor-2 transcription factor by calcium/calmodulin-dependent protein kinase-stimulated ...
AMP-activated protein kinase,. (3-metil-2-oksobutanoat dehidrogenaza (prenos acetila)) (EC 2.7.11.4) ... Protein kinaza C (EC 2.7.11.13). Protein kinaza C, Protein kinaza Cζ, PKC alfa, PRKCB1, PRKCD, PRKCE, PRKCH, PRKCG, PRKCI, ... "Protein kinase C and lipid signaling for sustained cellular responses" (ABSTRACT). FASEB J. 9 (7): 484-96. PMID 7737456. ... "The extended protein kinase C superfamily". Biochem. J. 332 ( Pt 2): 281-92. PMC 1219479. PMID 9601053. ...
cAMP binds to and releases an active form of protein kinase A (PKA). Next, PKA phosphorylates phosphorylase kinase, which, in ... Glycogen phosphorylase b is not always inactive in muscle, as it can be activated allosterically by AMP. An increase in AMP ... AMP activates glycogen phosphorylase b by changing its conformation from a tense to a relaxed form. This relaxed form has ... In the liver, glucagon activates another G-protein-linked receptor that triggers a different cascade, resulting in the ...
Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... protein kinase activity. • kinase activity. • protein serine/threonine kinase activity. • cyclin-dependent protein serine/ ... The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is highly similar to the gene ... Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene ...
... eryptosis is observed in red blood cells lacking the cGMP-dependent protein kinase type I or the AMP-activated protein kinase ... Protein 4.1R-based macromolecular complex - proteins interacting with Protein 4.1R. *Protein 4.1R - weak expression of Gerbich ... PIP2 enhances the binding of protein band 4.1R to glycophorin C but decreases its interaction with protein band 3, and thereby ... Structural role - The following membrane proteins establish linkages with skeletal proteins and may play an important role in ...
AANAT is activated through a protein kinase A system in which cyclic AMP (cAMP) is involved. The activation of AANAT leads to ... The presence of the protein RIBEYE and other proteins in both pinealocytes and sensory cells (both photoreceptors and hair ... The presence of proteins such as Munc13-1 indicates that they are important in neurotransmitter release. At night, synaptic ... The characteristic protein of synaptic ribbons is RIBEYE, as revealed by light and electron microscopy. In lower vertebrates, ...
G protein-coupled receptor kinase. *AMP-activated protein kinase. Monomeric. *ARFs. *Rabs ... the GTPase activating proteins (GAPs). Inhibitors[edit]. Another class of regulatory proteins, the Guanosine nucleotide ... The inactive form of GTPases (GDP-form) are activated by a class of proteins called Guanosine nucleotide exchange factors (GEFs ... GTP-binding protein regulators regulate G proteins in several different ways. Small GTPases act as molecular switches in ...
Hardie DG, Hawley SA (December 2001). "AMP-activated protein kinase: the energy charge hypothesis revisited". Bioessays 23 (12 ... Lin X, Ayrapetov M, Sun G (2005). "Characterization of the interactions between the active site of a protein tyrosine kinase ... Scheeff E, Bourne P (2005). "Structural evolution of the protein kinase-like superfamily". PLoS Comput Biol 1 (5): e49. doi: ... Saylor P, Wang C, Hirai T, Adams J (1998). "A second magnesium ion is critical for ATP binding in the kinase domain of the ...
Francesconi A, Duvoisin RM (2000). „Opposing effects of protein kinase C and protein kinase A on metabotropic glutamate ... 1998). „GTPase activating specificity of RGS12 and binding specificity of an alternatively spliced PDZ (PSD-95/Dlg/ZO-1) domain ... Grupe II i III receptora su vezana za inhibiciju kaskade cikličnog AMP, ali se razlikuju u njihovoj specifičnosti za agoniste. ... Metabotropni glutamatni receptor 1 (GRM1) je ljudski gen koji kodira mGluR1 protein.[1][2][3] ...
AMP-activated protein kinase,. (3-metil-2-oksobutanoat dehidrogenaza (prenos acetila)) (EC 2.7.11.4) ... Protein kinaza C (EC 2.7.11.13). Protein kinaza C, Protein kinaza Cζ, PKC alfa, PRKCB1, PRKCD, PRKCE, PRKCH, PRKCG, PRKCI, ... Receptor protein serin/treonin kinaza (EC 2.7.11.30). Koštani morfogenetski proteinski receptori (BMPR1, BMPR1A, BMPR1B, BMPR2 ... Više od 125 od 500+ poznatih ljudskih protein kinaza su serin/treonin kinaze (STK).[1] ...
"The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress" ... This approach was used to characterize the substrate specificity of a large number of protein kinases. The kinase specificity ... and that this phosphatidylinositol-3-kinase (PI-3-kinase) is activated by growth factors to produce novel 3'-phosphorylated ... May 1993). "Phosphoinositide 3-kinase is activated by phosphopeptides that bind to the SH2 domains of the 85-kDa subunit". J. ...
Also, it may be activated by a cAMP-dependent protein kinase (PKA). This pathway is significantly less effective than the first ... which is necessary for lipid mobilization in response to cyclic AMP, which itself is provided by the activation of Gs protein- ... protein binding. • hydrolase activity. • protein kinase binding. • serine hydrolase activity. Cellular component. • cytoplasm. ... It may be activated by two mechanisms.[14] *In the first, phosphorylated perilipin A causes it to move to the surface of the ...
These ROS drive cancer cell proliferation by activating kinases that drive cell cycle progression growth factors at low ... The LDHBx protein is seven amino acids longer than the LDHB (LDH-H) protein. This amino acid extension is generated by ... AMP, and Pi. The subsequent glycolytic flux, specifically production of NADH and pyruvate, exceeds the capacity for pyruvate ... LDHC is a testes-specific LDH protein, that is encoded by the LDHC gene. LDHBx is a peroxisome-specific LDH protein. LDHBx is ...
... roles of membrane structure and electrostatics in lipid-protein and protein-protein interactions". Biochimica et Biophysica ... The conformational transition from MsbA-closed-apo to MsbA-AMP-PNP involves two steps, which are more likely concerted: a ~10° ... Matte A, Tari LW, Delbaere LT (Apr 1998). "How do kinases transfer phosphoryl groups?". Structure. 6 (4): 413-9. doi:10.1016/ ... possibly related to the outward transport of the lipid platelet activating factor (PAF). It has also been reported that ABCB1 ...
Bound to serum proteinsEdit. The majority of thiamine in serum is bound to proteins, mainly albumin. Approximately 90% of total ... Bacterial thiaminases are cell surface enzymes that must dissociate from the membrane before being activated; the dissociation ... AMP (EC 2.7.6.2). ThDP is a coenzyme for several enzymes that catalyze the transfer of two-carbon units and in particular the ... by a thiamine-phosphate kinase (ThMP + ATP → ThDP + ADP, EC 2.7.4.16). In most bacteria and in eukaryotes, ThMP is hydrolyzed ...
Buhl AM, Osawa S, Johnson GL (1995). "Mitogen-activated protein kinase activation requires two signal inputs from the human ... phospholipase C-activating G-protein coupled receptor signaling pathway. • retina development in camera-type eye. • Ras protein ... protein complex binding. • signal transducer activity. • protein binding. • GTPase activity. • GTPase binding. • G-protein ... 1omw: Crystal Structure of the complex between G Protein-Coupled Receptor Kinase 2 and Heterotrimeric G Protein beta 1 and ...
AMOTL2: encoding protein Angiomotin-like protein 2. *ARHGAP31: Rho GRPase activating protein 31 ... ARPP-21: Cyclic AMP-regulated phosphoprotein, 21 kDa. *AZI2: encoding protein 5-azacytidine-induced protein 2 ... PIK3CA: phosphoinositide-3-kinase, catalytic, alpha polypeptide. *PROSER1: Proline and serine rich protein 1 ... C3orf14-Chromosome 3 open reading frame 14: predicted DNA binding protein.. *C3orf23: encoding protein Uncharacterized protein ...
"The AMP-activated protein kinase α2 catalytic subunit controls whole-body insulin sensitivity". The Journal of Clinical ... "The AMP-activated protein kinase α2 catalytic subunit controls whole-body insulin sensitivity". The Journal of Clinical ... "The AMP-activated protein kinase α2 catalytic subunit controls whole-body insulin sensitivity". The Journal of Clinical ... The AMP-activated protein kinase α2 catalytic subunit controls whole-body insulin sensitivity ,journal=The Journal of Clinical ...
... mitogen-activated-protein kinase-activating protein kinase) has a preference for Ser40, but also phosphorylates Ser19 about ... "Direct phosphorylation of brain tyrosine hydroxylase by cyclic AMP-dependent protein kinase: mechanism of enzyme activation". ... kinase and MAP-kinase-activated kinases 1 and 2". European Journal of Biochemistry / FEBS. 217 (2): 715-22. doi:10.1111/j.1432- ... that are phosphorylated by a variety of protein kinases.[12][25] Ser40 is phosphorylated by the cAMP-dependent protein kinase.[ ...
Hardie DG, Hawley SA (Detsember 2001). "AMP-activated protein kinase: the energy charge hypothesis revisited". BioEssays 23 (12 ... Üha enam hakatakse aga kasutama sellist energiahulka, mis arvestab lisaks ATP ja ADP kogusele ka AMP kogust. Selle reaktsiooni ... Rakud kasutavad ATP ja AMP koguste vahelist suhet mitmeks otstarbeks. Esiteks selleks, et teha kindlaks, kui palju energiat, ... ATP + H2O → AMP + PPi ΔG˚ = −45,6 kJ/mol (−10,9 kcal/mol) ...
"Biochemical characterization of the human cyclin-dependent protein kinase activating kinase. Identification of p35 as a novel ... AMP. The A and B transferases are the foundation of the human ABO blood group system. Both A and B transferases are ... A prominent kinase is cyclin-dependent kinase (or CDK), which comprises a sub-family of protein kinases. As their name implies ... Zhu X, Sen J, Stevens L, Goltz JS, Stein D (Sep 2005). "Drosophila pipe protein activity in the ovary and the embryonic ...
... nuclear located protein kinase C and cyclic AMP-dependent protein kinase". 》Frontiers in Bioscience》 13 (13): 1206-26. doi: ... May 2006). "Kdo2-Lipid A of Escherichia coli, a defined endotoxin that activates macrophages via TLR-4". 》Journal of Lipid ... Parodi AJ, Leloir LF (April 1979). "The role of lipid intermediates in the glycosylation of proteins in the eucaryotic cell". 》 ... The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis". 》Journal ...
阿司匹林在體內分解為水楊酸,而水楊酸本身則有抗炎、退燒、鎮痛等作用。2012年發現水楊酸還能激活AMP活化蛋白激酶(英語:AMP-activated protein kinase),這是水楊酸和阿司匹林藥效的一種可能的解釋。[134][135] 阿司匹林 ... The Ancient Drug Salicylate Directly Activates AMP-Activated Protein Kinase. Science. 2012, 336 (6083): 918-922. PMC 3399766. ... REG1(英語:REG1) · 去纖苷(英語:Defibrotide) · 雷馬曲
Viollet B, Andreelli F, Jørgensen SB, et al (January 2003). "The AMP-activated protein kinase alpha2 catalytic subunit controls ... Viollet B, Andreelli F, Jørgensen SB, et al (January 2003). "The AMP-activated protein kinase alpha2 catalytic subunit controls ... Viollet B, Andreelli F, Jørgensen SB, et al (January 2003). "The AMP-activated protein kinase alpha2 catalytic subunit controls ... cite journal ,author=Viollet B; Andreelli F; Jørgensen SB ''et al'' ,title=The AMP-activated protein kinase alpha2 catalytic ...
... p38 mitogen-activated protein kinases (p38 Mpk), and cAMP response element-binding protein (CREB) which when activated ... production of cyclic AMP [cAMP]);[5] e) G proteins types to which they link and activate, i.e. those containing the Gs alpha ... activating prostanoids. classification[5]. G protein linkage[2]. pathways[2] Prostaglandin DP1 receptor. DP1. PGD2,,PGE2,PGF2α, ... cell signaling agents and for activating protein kinase C (PKC) secondary messengers; and Extracellular signal-regulated ...
... leading to the activation of the AMP-activated protein kinase (AMPK). AMPK is the main kinase regulator of ACC, able to ... Protein kinase A also has the ability to phosphorylate ACC, with a much greater ability to phosphorylate ACC2 than ACC1. ... Control of Acetyl CoA Carboxylase. The AMP regulated kinase triggers the phosphorylation of the enzyme (thus inactivating it) ... When insulin binds to its receptors on the cellular membrane, it activates a phosphatase enzyme called protein phosphatase 2A ( ...
AMP-activated protein kinase,. (3-metil-2-oksobutanoat dehidrogenaza (prenos acetila)) (EC 2.7.11.4) ... 1997). „Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proc. Natl. Acad. Sci. U.S ... 1997). „Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2". EMBO J. ENGLAND. 16 (8): 1909- ... 2003). „The N and C termini of the splice variants of the human mitogen-activated protein kinase-interacting kinase Mnk2 ...
Identification of four sites phosphorylated in intact cells and in vitro by cyclic AMP-dependent protein kinase and p34cdc2". ... "Serine 25 of oncoprotein 18 is a major cytosolic target for the mitogen-activated protein kinase". The Journal of Biological ... Regulation of stathmin is cell cycle dependent and controlled by the cell's protein kinases in response to specific cell ... Maucuer A, Camonis JH, Sobel A (April 1995). "Stathmin interaction with a putative kinase and coiled-coil-forming protein ...
cAMP can then act as a second messenger that goes on to interact with and activate protein kinase A (PKA). PKA can ... Gαs activates the cAMP-dependent pathway by stimulating the production of cyclic AMP (cAMP) from ATP. This is accomplished by ... Whereas G proteins are activated by G protein-coupled receptors, they are inactivated by RGS proteins (for "Regulator of G ... A group of proteins called Regulator of G protein signalling (RGSs), act as GTPase-activating proteins (GAPs), are specific for ...
The AMP-activated protein kinase (AMPK) is a metabolic-stress-sensing protein kinase that regulates metabolism in response to ... AMP-activated protein kinase, super metabolic regulator.. Kemp BE1, Stapleton D, Campbell DJ, Chen ZP, Murthy S, Walter M, ... Protein-Serine-Threonine Kinases/genetics. *Protein-Serine-Threonine Kinases/metabolism. *Protein-Serine-Threonine Kinases/ ...
Activation of yeast Snf1 and mammalian AMP-activated protein kinase by upstream kinases. Seung-Pyo Hong, Fiona C. Leiper, ... The Snf1/AMP-activated protein kinase (AMPK) family of kinases is important for metabolic stress responses in eukaryotes ( ... Activation of yeast Snf1 and mammalian AMP-activated protein kinase by upstream kinases ... Activation of yeast Snf1 and mammalian AMP-activated protein kinase by upstream kinases ...
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 ...
The kinases are heterotrimers that comprise a catalytic subunit and regulatory subunits that sense cellular energy levels. When ... The SNF1/AMP-activated protein kinase (AMPK) family maintains the balance between ATP production and consumption in all ... AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy Nat Rev Mol Cell Biol. 2007 Oct;8(10):774-85. doi: ... The SNF1/AMP-activated protein kinase (AMPK) family maintains the balance between ATP production and consumption in all ...
"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". ...
It is activated by stresses causing ATP depletion and, once activated, maintains energy homeostasis by phosphorylating targets ... that activate catabolism and inhibit energy-consuming processes. Evidence derived from non-mammali … ... AMP-activated protein kinase: also regulated by ADP? Trends Biochem Sci. 2011 Sep;36(9):470-7. doi: 10.1016/j.tibs.2011.06.004 ... We review recent findings showing that AMPK is activated by ADP as well as AMP, and discuss the mechanism by which binding of ...
A specific method for activating AMP-activated protein kinase in intact cells? Eur. J. Biochem. 1995. 229:558-565. View this ... AMP-activated protein kinase is activated by low glucose in cell lines derived from pancreatic beta cells, and may regulate ... Characterization of the AMP-activated protein kinase kinase from rat liver and identification of threonine 172 as the major ... AMP-activated protein kinase (AMPK); 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR); kinase-dead AMPKα2 transgenic ...
AMP-activated protein kinase (AMPK) is viewed as a fuel sensor for glucose and lipid metabolism. To better understand the ... The AMP-activated protein kinase α2 catalytic subunit controls whole-body insulin sensitivity. ... The AMP-activated protein kinase α2 catalytic subunit controls whole-body insulin sensitivity. ...
"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 ...
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, ...
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. ...
... 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 ...
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 · ...
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. ...
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 ...
Markers of brown-like (beige) adipogenesis were measured and the involvement of AMP-activated protein kinase (AMPK) α1 was ... Resveratrol significantly increased mRNA and/or protein expression of brown adipocyte markers, including uncoupling protein 1 ( ... UCP1), PR domain-containing 16, cell death-inducing DFFA-like effector A, elongation of very long-chain fatty acids protein 3, ... peroxisome proliferator-activated receptor-γ coactivator 1α, cytochrome c and pyruvate dehydrogenase, in differentiated iWAT ...
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 ...
New targets of AMP-activated protein kinase L. Hue; L. Hue 1 ... The discovery of the AMP-activated protein kinase (AMPK) more ... New targets of AMP-activated protein kinase. Biochem Soc Trans 1 February 2003; 31 (1): 213-215. doi: https://doi.org/10.1042/ ... Measurement of tumour protein synthesis in vivo in human colorectal and breast cancer and its variability in separate biopsies ... All conditions known to increase this ratio activate AMPK, whose major role is to act as an emergency signal to conserve ATP. ...
... domain and a peptide optimized for phosphorylation by AMP-Activated Protein Kinase (AMPK), which has previously been exploited ... can serve as a readout for a highly sensitive two-step AMPK AlphaScreen kinase assay with exceptional signal-to-noise ratio. ... While many methods exist to quantitatively determine protein kinase activities, 32P-based radioactive assays remain the ... AMP-activated protein kinase (AMPK); Forkhead-associated (FHA) domain; kinase assay; AlphaScreen AMP-activated protein kinase ( ...
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 ...
... 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. ...
Protein. Similar proteins. Species. Score. Length. Source. G3Q2F9. 5-AMP-activated protein kinase beta-2 non-catalytic subunit ... Protein kinase, AMP-activated, beta 1 non-catalytic subunit, aImported. ,p>Information which has been imported from another ... tr,G3Q2F9,G3Q2F9_GASAC Protein kinase, AMP-activated, beta 1 non-catalytic subunit, a OS=Gasterosteus aculeatus OX=69293 PE=4 ... 5-AMP-activated protein kinase subunit beta-2. OPIHO. 275. 5-AMP-activated protein kinase subunit beta-2 (Fragment). ...
AMP-activated/SNF1 protein kinases: Conserved guardians of cellular energy. Nat. Rev. Mol. Cell Biol. 8, 774 (2007). doi: ... Functional domains of the α1 catalytic subunit of the AMP-activated protein kinase. J. Biol. Chem. 273, 35347 (1998). doi: ... Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy ... Adenosine monophosphate-activated protein kinase (AMPK) is a conserved sensor of intracellular energy activated in response to ...
... improves energy status and inhibits AMP-activated protein kinase signalling pathways in weaned piglets challenged with ... 14 Sanli, T, Steinberg, GR, Singh, G, et al. (2014) AMP-activated protein kinase (AMPK) beyond metabolism: a novel genomic ... 41 Hardie, DG & Hawley, SA (2001) AMP-activated protein kinase: the energy charge hypothesis revisited. Bioessays 23, 1112-1119 ... 47 Hardie, DG (2003) Minireview: the AMP-activated protein kinase cascade: the key sensor of cellular energy status. ...
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 ...
PRKAB1, protein kinase AMP-activated non-catalytic subunit beta 1. Orthology source: HomoloGene, HGNC ... IPR039160 5-AMP-activated protein kinase subunit beta. IPR032640 AMP-activated protein kinase, glycogen-binding domain ... protein coding gene. Chr5:116013586-116024508 (-). 129S1/SvImJ MGP_129S1SvImJ_G0029978. protein coding gene. Chr5:118948579- ... protein coding gene. Chr5:128254162-128265084 (-). DBA/2J MGP_DBA2J_G0029791. protein coding gene. Chr5:114287245-114298027 (-) ...
AMP-activated protein kinase (AMPK) plays a key role as a master regulator of cellular energy homeostasis. The kinase is ... AMP-activated protein kinase regulates HNF4alpha transcriptional activity by inhibiting dimer formation and decreasing protein ... AMP-activated Protein Kinase (AMPK) Signaling (Homo sapiens). From WikiPathways. Revision as of 16:01, 15 March 2011 by ... Viana R, Aguado C, Esteban I, Moreno D, Viollet B, Knecht E, Sanz P; Role of AMP-activated protein kinase in autophagy and ...
... 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 ...
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. ...
... protein kinase A; PKC, protein kinase C; MAPK, mitogen-activated protein kinase; CREB, CRE-binding protein; ATF, activating ... The Involvement of Tyrosine Kinases, Cyclic AMP/Protein Kinase A, and p38 Mitogen-Activated Protein Kinase in IL-13-Mediated ... The Involvement of Tyrosine Kinases, Cyclic AMP/Protein Kinase A, and p38 Mitogen-Activated Protein Kinase in IL-13-Mediated ... The Involvement of Tyrosine Kinases, Cyclic AMP/Protein Kinase A, and p38 Mitogen-Activated Protein Kinase in IL-13-Mediated ...
  • AMP-activated protein kinase (AMPK), an energy sensor, can regulate protein and lipid metabolism responding to alterations in energy supply. (medscape.com)
  • The AMP-activated protein kinase (AMPK) is a metabolic-stress-sensing protein kinase that regulates metabolism in response to energy demand and supply by directly phosphorylating rate-limiting enzymes in metabolic pathways as well as controlling gene expression. (nih.gov)
  • The Snf1/AMP-activated protein kinase (AMPK) family plays fundamental roles in cellular responses to metabolic stress in eukaryotes. (pnas.org)
  • Snf1 and AMPK are the downstream components of kinase cascades, but the upstream kinase(s) have remained elusive. (pnas.org)
  • Moreover, Tos3p phosphorylates mammalian AMPK on the equivalent residue and activates the enzyme, suggesting functional conservation of the upstream kinases between yeast and mammals. (pnas.org)
  • We further show that the closely related mammalian LKB1 kinase, which is associated with Peutz-Jeghers cancer-susceptibility syndrome, phosphorylates and activates AMPK in vitro . (pnas.org)
  • The Snf1/AMP-activated protein kinase (AMPK) family of kinases is important for metabolic stress responses in eukaryotes (reviewed in refs. (pnas.org)
  • In mammals, AMPK is activated by multiple stresses that lead to an increase in the cellular AMP:ATP ratio and is also activated by leptin ( 3 ) and metformin, a drug used to treat type 2 diabetes ( 4 ). (pnas.org)
  • The Snf1 kinase comprises the catalytic subunit Snf1p (α subunit of AMPK), Snf4p (γ subunit of AMPK), and one of three β subunits. (pnas.org)
  • Snf1 is activated by phosphorylation of the activation-loop threonine residue ( 8 , 11 , 19 , 20 ), as is also the case for AMPK ( 21 ). (pnas.org)
  • Despite intensive efforts, the identities of the upstream kinases that phosphorylate Snf1 and AMPK have proved elusive. (pnas.org)
  • We further show that Tos3p phosphorylates and activates AMPK in vitro , suggesting that the mammalian upstream kinase(s) are related to these yeast kinases. (pnas.org)
  • We therefore searched for closely related mammalian kinases and found that the LKB1 tumor suppressor kinase ( 25 , 26 ) activates AMPK in vitro . (pnas.org)
  • The AMP-activated protein kinase (AMPK) is a member of a metabolite-sensing protein kinase family that is found in all eukaryotes. (nih.gov)
  • The SNF1/AMP-activated protein kinase (AMPK) family maintains the balance between ATP production and consumption in all eukaryotic cells. (nih.gov)
  • 5' AMP-activated protein kinase or AMPK or 5' adenosine monophosphate-activated protein kinase is an enzyme (EC 2.7.11.31) that plays a role in cellular energy homeostasis, largely to activate glucose and fatty acid uptake and oxidation when cellular energy is low. (wikipedia.org)
  • In response to binding AMP and ADP, the net effect of AMPK activation is stimulation of hepatic fatty acid oxidation, ketogenesis, stimulation of skeletal muscle fatty acid oxidation and glucose uptake, inhibition of cholesterol synthesis, lipogenesis, and triglyceride synthesis, inhibition of adipocyte lipogenesis, inhibition of adipocyte lipolysis, and modulation of insulin secretion by pancreatic beta-cells. (wikipedia.org)
  • It should not be confused with cyclic AMP-activated protein kinase (protein kinase A). AMPK is a heterotrimeric protein complex that is formed by α, β, and γ subunits. (wikipedia.org)
  • Specifically, the γ subunit includes four particular Cystathionine beta synthase (CBS) domains, giving AMPK its ability to sensitively detect shifts in the AMP:ATP ratio. (wikipedia.org)
  • It is in this catalytic domain where AMPK becomes activated when phosphorylation takes place at threonine-172 by an upstream AMPK kinase (AMPKK). (wikipedia.org)
  • The following human genes encode AMPK subunits: α - PRKAA1, PRKAA2 β - PRKAB1, PRKAB2 γ - PRKAG1, PRKAG2, PRKAG3 The crystal structure of mammalian AMPK regulatory core domain (α C terminal, β C terminal, γ) has been solved in complex with AMP, ADP or ATP. (wikipedia.org)
  • AMPK is regulated allosterically mostly by competitive binding on its gamma subunit between ATP (which allows phosphatase access to T172) and AMP or ADP (each of which blocks access to phosphatases). (wikipedia.org)
  • It thus appears that AMPK is a sensor of AMP/ATP or ADP/ATP ratios and thus cell energy level. (wikipedia.org)
  • Regulation of AMPK by CaMKK2 requires a direct interaction of these two proteins via their kinase domains. (wikipedia.org)
  • The interaction of CaMKK2 with AMPK only involves the alpha and beta subunits of AMPK (AMPK gamma is absent from the CaMKK2 complex), thus rendering regulation of AMPK in this context to changes in calcium levels but not AMP or ADP. (wikipedia.org)
  • AMPK may be inhibited or activated by various tissue-specific ubiquitinations. (wikipedia.org)
  • When AMPK phosphorylates acetyl-CoA carboxylase 1 (ACC1) or sterol regulatory element-binding protein 1c (SREBP1c), it inhibits synthesis of fatty acids, cholesterol, and triglycerides, and activates fatty acid uptake and β-oxidation. (wikipedia.org)
  • AMPK stimulates glucose uptake in skeletal muscle by phosphorylating Rab-GTPase-activating protein TBC1D1, which ultimately induces fusion of GLUT1 vesicles with the plasma membrane. (wikipedia.org)
  • It is the catalytic subunit of the 5'-prime-AMP-activated protein kinase (AMPK). (wikipedia.org)
  • The kinase activity of AMPK is activated by the stimuli that increase the cellular AMP/ATP ratio. (wikipedia.org)
  • AMP-activated protein kinase (AMPK) is viewed as a fuel sensor for glucose and lipid metabolism. (jci.org)
  • The aim of this study was to investigate the effect of nicotine on hypothalamic AMP-activated protein kinase (AMPK) and its effect on energy balance. (diabetesjournals.org)
  • An important mediator of all of these effects is hypothalamic AMP-activated protein kinase (AMPK), a cellular gauge that controls whole-body energy balance and is activated in conditions of low energy ( 14 , 15 ). (diabetesjournals.org)
  • When activated, AMPK optimizes energy utilization by increasing energy-producing and reducing energy-wasting processes at the whole-body level. (diabetesjournals.org)
  • Activated AMPK is also an important regulator of fatty acid biosynthesis, suppressing de novo lipogenesis by phosphorylation and inactivation of acetyl-CoA carboxylase (ACC) ( 7 , 8 , 14 , 15 , 17 , 18 ). (diabetesjournals.org)
  • 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. (diabetesjournals.org)
  • 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. (diabetesjournals.org)
  • Cellular protein synthesis is believed to be antagonistically regulated by mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) signaling pathways. (springer.com)
  • In the present study, we examined the relationship between mTOR/p70 S6 kinase (p70S6K) and AMPK in response to mechanical stretch. (springer.com)
  • 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. (clinicaltrials.gov)
  • Adenosine monophosphate-activated protein kinase (AMPK) is a crucial regulator of energy metabolic homeostasis and thus a major survival factor in a variety of metabolic stresses and also in the aging process. (springer.com)
  • Interestingly, many target proteins of AMPK are so-called longevity factors, e.g. (springer.com)
  • AMPK is a serine/threonine kinase which has been highly conserved during evolution. (springer.com)
  • AMPK is activated via allosteric regulation of increased AMP concentration and by the phosphorylation of α subunit (Thr172) via the upstream kinases serine/threonine kinase 11 (LKB1), Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ), and transforming growth factor-β-activated kinase 1. (springer.com)
  • One major role of AMPK signaling is to respond to metabolic requirements either by stimulating energy production including glucose and lipid catabolism or by inhibiting energy consuming pathways, e.g., synthesis of protein, fatty acids, and cholesterol. (springer.com)
  • The specific signal pathways of AMP-activated protein kinase (AMPK), eNOS/Akt, and heme oxygenase-1 (HO-1) were also assessed. (hindawi.com)
  • Markers of brown-like (beige) adipogenesis were measured and the involvement of AMP-activated protein kinase (AMPK) α1 was assessed using conditional knockout. (nature.com)
  • The 5′-AMP (adenosine monophosphate)-activated protein kinase (AMPK) coordinates metabolic function with energy availability by responding to changes in intracellular ATP (adenosine triphosphate) and AMP concentrations. (sciencemag.org)
  • Here, we report crystal structures at 2.9 and 2.6 Å resolution for ATP- and AMP-bound forms of a core αβγ adenylate-binding domain from the fission yeast AMPK homolog. (sciencemag.org)
  • The discovery of the AMP-activated protein kinase (AMPK) more than a decade ago has shed much light on the cellular response to stresses characterized by a fall in the concentration of ATP and an increase in the AMP/ATP ratio. (portlandpress.com)
  • All conditions known to increase this ratio activate AMPK, whose major role is to act as an emergency signal to conserve ATP. (portlandpress.com)
  • Metformin also attenuated oxidative stress and malondialdehyde-containing protein levels, with corresponding induction of antioxidative defenses in OLs exposed to cytokines via AMPK activation. (wellnessresources.com)
  • Here, we demonstrate that the interaction between the yeast Rad53 Forkhead-associated (FHA) domain and a peptide optimized for phosphorylation by AMP-Activated Protein Kinase (AMPK), which has previously been exploited for the generation of intracellular phosphorylation sensors, can serve as a readout for a highly sensitive two-step AMPK AlphaScreen kinase assay with exceptional signal-to-noise ratio. (mdpi.com)
  • ATP-consumption during re-esterification of FAs after lipolysis may also activate AMPK (3), such that regulation of lipolysis by AMPK is likely to be dependent on the duration and mode of AMPK activation. (clinsci.org)
  • Anti-inflammatory actions of AMPK in adipose tissue In lean adipose tissue, small adipocytes and alternatively activated macrophages secrete adipocytokines such as IL-10 and adiponectin, which maintain an anti-inflammatory environment. (clinsci.org)
  • Production of these adipocytokines is promoted by activated AMPK. (clinsci.org)
  • Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. (uniprot.org)
  • 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. (uniprot.org)
  • Adenosine monophosphate-activated protein kinase (AMPK) is a conserved sensor of intracellular energy activated in response to low nutrient availability and environmental stress. (sciencemag.org)
  • In a screen for conserved substrates of AMPK, we identified ULK1 and ULK2, mammalian orthologs of the yeast protein kinase Atg1, which is required for autophagy. (sciencemag.org)
  • Finally, Asn administration decreased the mRNA abundance of intestinal AMP-activated protein kinase-α1 ( AMPKα1 ), AMPKα2 , silent information regulator 1 ( SIRT1 ) and PPARγ coactivator-1α ( PGC1α ), and reduced intestinal AMPKα phosphorylation. (cambridge.org)
  • the current model states that binding of AMP to the gamma subunit leads to conformational changes that allosterically activate AMPK and render phosphorylated-Thr172 unavailable for inhibitory dephosphorylation. (wikipathways.org)
  • AMPK inhibits mTOR signaling pathway by activating Tsc2 and downstream of Tsc2 by inhibiting Raptor component of mTOR complex 1 [note that this effect is opposite to Tsc2 phosphorylation and inactivation by PI3K-Akt signaling downstream of insulin]. (wikipathways.org)
  • As a note, drugs used in the treatment of insulin resistance and diabetes can activate AMPK. (wikipathways.org)
  • AMP-activated protein kinase (AMPK) plays a key role as a master regulator of cellular energy homeostasis. (wikipathways.org)
  • Binding of AMP to the γ subunit allosterically activates the complex, making it a more attractive substrate for its major upstream AMPK kinase, LKB1. (wikipathways.org)
  • Several studies indicate that signaling through adiponectin, leptin and CAMKKβ may also be important in activating AMPK. (wikipathways.org)
  • AMPK negatively regulates several proteins central to ATP consuming processes such as TORC2, glycogen synthase, SREBP-1 and TSC2, resulting in the downregulation or inhibition of gluconeogenesis, glycogen, lipid and protein synthesis. (wikipathways.org)
  • Akt activates the mammalian target of rapamycin by regulating cellular ATP level and AMPK activity. (wikipathways.org)
  • Protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1), also known as AMPK α1, is an energy sensor that plays a key role in the regulation of cellular energy metabolism. (atlasgeneticsoncology.org)
  • AMPK α1 is the catalytic subunit of the heterotrimeric AMPK protein with a length of 548 amino acids. (atlasgeneticsoncology.org)
  • The human AMPK α1 gene has 9 transcripts: PRKAA1-201 (1134 bp), PRKAA1-202 (1918 bp), PRKAA1-204 (5088 bp) that code for a protein. (atlasgeneticsoncology.org)
  • In response to an increase in the AMP/ATP ratio, AMPK gets activated. (atlasgeneticsoncology.org)
  • AMP binds to the non-catalytic gamma subunit of the AMPK protein and induces phosphorylation of Thr-183 (Lizcano et al. (atlasgeneticsoncology.org)
  • There are several known AMPK kinases (AMPKKs). (atlasgeneticsoncology.org)
  • STK11 (LKB1), complexed with STRADA and CAB39 (MO25), is the major upstream regulator of the AMPK, which phosphorylates the AMP bound protein (Shackelford and Shaw, 2009). (atlasgeneticsoncology.org)
  • Ca2+/calmodulin-dependent protein kinase kinase β ( CAMKK2 or CaMKKβ) is also known to be an upstream kinase of AMPK (Sundararaman et al. (atlasgeneticsoncology.org)
  • 2016). TGF-beta-activated kinase-1 ( MAP3K7 or TAK1) may also phosphorylate AMPK α or at least play a role in its activation as loss of TAK1 leads to impaired AMPK activation (Xie et al. (atlasgeneticsoncology.org)
  • The AMPK α1 protein consists of several domains (Figure 1). (atlasgeneticsoncology.org)
  • AMP-activated protein kinase (AMPK) activity increases in response to depletion of cellular energy stores, and this enzyme has been implicated in the stimulation of glucose uptake into skeletal muscle and the inhibition of liver gluconeogenesis. (diabetesjournals.org)
  • We recently reported that AMPK is activated by metformin in cultured rat hepatocytes, mediating the inhibitory effects of the drug on hepatic glucose production. (diabetesjournals.org)
  • AMP-activated protein kinase (AMPK) is a heterotrimeric enzyme composed of a catalytic subunit (α) and two regulatory subunits (β and γ) ( 9 , 10 ). (diabetesjournals.org)
  • AMPK works as an intracellular fuel gauge that becomes activated by decreases in the ATP/ADP and phosphocreatine (PCr)/creatine ratios through mechanisms involving phosphorylation by one or more upstream AMPK kinases, allosteric activation, and a decrease in the inhibitory action of phosphatases ( 9 , 12 , 13 ). (diabetesjournals.org)
  • AICAR cannot stimulate muscle glucose uptake in mice carrying a kinase-dead AMPK mutant in muscle ( 19 ). (diabetesjournals.org)
  • Previous studies have shown that ATP treatment leads to AMP-activated protein kinase (AMPK) activation. (frontiersin.org)
  • Our results showed that AMPK signaling was activated in murine macrophages upon ATP treatment, which was accompanied by inflammasome activation and pyroptosis as evidenced by rapid cell membrane rupture as well as mature interleukin (IL)-1β and active caspase-1p10 release. (frontiersin.org)
  • AMP-activated protein kinase (AMPK) is an enzyme that senses and regulates cellular energy balance thus playing a key role in homeostasis. (bl.uk)
  • AMPK is primarily activated by phosphorylation at Thr-172 on the activation loop in the kinase domain. (bl.uk)
  • A number of mutations in the γ subunit, which interfere with the normal function of AMPK and cause Wolff-Parkinson- White (WPW) syndrome, have also assessed for changes in nucleotide binding affinities and potential implications for the regulation of kinase activity. (bl.uk)
  • This protein constitutes a regulatory subunit of the AMP-activated protein kinase (AMPK). (atlasgeneticsoncology.org)
  • The heterotrimeric protein AMPK senses low intracellular energy levels upon increased in the AMP/ATP ratio. (atlasgeneticsoncology.org)
  • Among these substrates is the tuberin protein, the product of the tuberous sclerosis complex 2 gene ( TSC2 ) that upon activation by AMPK represses the activity of the mammalian target of rapamycin, mTOR . (atlasgeneticsoncology.org)
  • LKB1 is a serine/threonin kinase that phosphorylates and activates AMPK. (atlasgeneticsoncology.org)
  • The AMP-activated protein kinase (AMPK) is a Ser/Thr kinase that is activated in response to low-energy states to coordinate multiple signaling pathways to maintain cellular energy homeostasis. (jneurosci.org)
  • Furthermore, we found that eukaryotic elongation factor 2 (eEF2) and its kinase eEF2K are key downstream effectors that mediate the detrimental effects of hyperactive AMPK in AD pathophysiology. (jneurosci.org)
  • One of the signaling molecules that could be a therapeutic target for AD is the AMP-activated protein kinase (AMPK). (jneurosci.org)
  • The AMP-activated protein kinase (AMPK) is an important cellular energy sensor. (frontiersin.org)
  • An essential actor in the phospho-dependent metabolic reorganization during energy stress is the AMP-activated protein kinase (AMPK) ( 2 ). (frontiersin.org)
  • It has been recently shown that AMPK can interrelate with enzymes regulating protein O-GlcNAcylation. (frontiersin.org)
  • AMPK is a heterotrimeric protein composed of one catalytic subunit α (existing in two isoforms, α1, and α2) and two regulatory subunits, β (β1 and β2) and γ (γ1, γ2, and γ3) ( 8 ). (frontiersin.org)
  • BPE treatment decreased triglyceride accumulation in both 3T3-L1 adipocytes and HepG2 hepatocytes by activating AMP-activated protein kinase (AMPK) signaling and regulating the expression of lipid metabolism-related proteins. (biomedsearch.com)
  • BPE also activated AMPK signaling and altered the expression of lipid metabolism-related proteins in white adipose tissue and liver. (biomedsearch.com)
  • Taken together, these findings indicate that BPE attenuates HFD-induced obesity by activating AMPK and regulating lipid metabolism, suggesting a potent anti-obesity agent. (biomedsearch.com)
  • AMPK (AMP-activated protein kinase) is a key regulator of cellular and whole-body energy balance. (clinsci.org)
  • AMPK phosphorylates and regulates many proteins concerned with nutrient metabolism, largely acting to suppress anabolic ATP-consuming pathways while stimulating catabolic ATP-generating pathways. (clinsci.org)
  • The adenosine monophosphate (AMP)-activated protein kinase (AMPK) has a crucial role in maintaining cellular energy homeostasis. (rupress.org)
  • This study shows that human and mouse T lymphocytes express AMPKα1 and that this is rapidly activated in response to triggering of the T cell antigen receptor (TCR). (rupress.org)
  • However, TCR and Ca 2+ stimulation of AMPK required the activity of Ca 2+ -calmodulin-dependent protein kinase kinases (CaMKKs), whereas AMPK activation induced by increased AMP/ATP ratios did not. (rupress.org)
  • The rapid activation of AMPK in response to Ca 2+ signaling in T lymphocytes thus reveals that TCR triggering is linked to an evolutionally conserved serine kinase that regulates energy metabolism. (rupress.org)
  • In this respect, recent studies have suggested that CaMKKs also have the potential to activate the AMP-activated protein kinase (AMPK), a protein kinase with a crucial role in maintaining cellular energy homeostasis ( 12 - 14 ). (rupress.org)
  • AMPK can be activated by an increased intracellular AMP/ATP ratio, which is a marker of falling cellular energy status, and acts to restore energy balance by inhibiting ATP-consuming processes and stimulating ATP-generating pathways ( 15 ). (rupress.org)
  • The stimulation of AMPK by an increase in the AMP/ATP ratio requires the phosphorylation of Thr-172 by the kinase LKB1 ( 16 , 17 ). (rupress.org)
  • Three enzymes, namely AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC) and malonyl-CoA decarboxylase (MCD), appear to be extremely important in this process. (portlandpress.com)
  • In addition, it is suggested that AMPK also phosphorylates and activates MCD, promoting degradation of malonyl-CoA levels. (portlandpress.com)
  • In ischaemia, AMPK is rapidly activated and inhibits ACC, subsequently decreasing malonyl-CoA levels and increasing fatty acid oxidation rates. (portlandpress.com)
  • The AMP-activated protein kinase (AMPK) was initially identified as the kinase that phosphorylates the 3-hydroxy 3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme for cholesterol biosynthesis. (ahajournals.org)
  • As the name suggests, the AMPK is activated by increased intracellular concentrations of AMP, and is generally described as a "metabolite-sensing kinase" and when activated initiates steps to conserve cellular energy. (ahajournals.org)
  • To date the AMPK in endothelial cells has been implicated in the regulation of fatty acid oxidation, small G protein activity and nitric oxide production as well as inflammation and angiogenesis. (ahajournals.org)
  • The AMP-activated protein kinase (AMPK) is a heterotrimeric serine/threonine protein kinase consisting of the catalytic subunit (α) and 2 regulatory subunits (β and γ) that exist as multiple isoforms and splice variants, resulting in the generation of 12 possible heterotrimeric combinations. (ahajournals.org)
  • As its name suggests, the AMPK is activated in many different cell types by increased intracellular concentrations of AMP and is generally referred to as a "metabolite-sensing kinase. (ahajournals.org)
  • Each subunit within the heterotrimeric AMPK complex has a distinct structure and function and their interaction is necessary for the modulation of kinase activity. (ahajournals.org)
  • For example, whereas the AMP-insensitive α1 isoform predominates in adipose tissue and skeletal muscle, cardiomyocytes express much higher amounts of the AMPKα2. (ahajournals.org)
  • An increasing body of evidence has linked AMP-activated protein kinase (AMPK) and malonyl coenzyme A (CoA) to the regulation of energy balance. (garvan.org.au)
  • Thus, factors that activate AMPK and decrease the concentration of malonyl CoA in peripheral tissues, such as exercise, decrease triglyceride accumulation in the adipocyte and other cells. (garvan.org.au)
  • AMP-activated protein kinase (AMPK) is a multifunctional kinase that negatively regulates the mechanistic target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) signaling, two signaling pathways linked to pain promotion after injury, such as surgical incision. (aspetjournals.org)
  • AMPK can be activated directly using positive allosteric modulators, as well as indirectly through the upregulation of upstream kinases, such as liver kinase B1 (LKB1), which is a mechanism of action of metformin. (aspetjournals.org)
  • Because AMPK phosphorylation is required for kinase activity, we interpret our findings as evidence that indirect AMPK activators are more effective for treating pain hypersensitivity after incision because they can drive increased p-AMPK through upstream kinases like LKB1. (aspetjournals.org)
  • Our work focused on whether direct or indirect AMP-activated protein kinase (AMPK) activators would show greater efficacy for inhibiting incisional pain, and we also tested for potential sex differences. (aspetjournals.org)
  • Objective- Transforming growth factor-β-activated kinase 1 (TAK1) is a mitogen-activated protein 3-kinase and an AMP-activated protein kinase (AMPK) kinase in some cell types. (ahajournals.org)
  • TAK1 inhibition and downregulation also inhibited VEGF-stimulated phosphorylation of several kinases, including AMPK. (ahajournals.org)
  • In a DER dose-dependent manner, levels of Thr 172 phosphorylated AMP-activated protein kinase (AMPK) increased in mammary carcinomas with a concomitant increase in phosphorylated acetyl-CoA-carboxylase, a direct target of AMPK, the phosphorylation of which is regarded as an indicator of AMPK activity. (aacrjournals.org)
  • We hypothesized that DER would activate an ancient intracellular fuel sensor, AMP-activated protein kinase (AMPK), and, in concert with DER effects on IGF-I signaling that are mediated via protein kinase B (Akt), would work to down-regulate the activity of the mammalian target of rapamycin (mTOR). (aacrjournals.org)
  • Measurement of AMPK activation served as a primary end point for this work because a growing body of evidence indicates that AMPK functions as a fuel sensor in many tissues and organs where it inhibits anabolic pathways when cellular ATP levels are reduced and when AMP increases in response to limited energy availability ( 13 ). (aacrjournals.org)
  • We showed previously that α-lipoic acid (ALA) activates AMP-activated protein kinase (AMPK) and reduces lipid accumulation in skeletal muscle of obese rats. (ahajournals.org)
  • Here, we investigated whether ALA improves endothelial dysfunction in obese rats by activating AMPK in endothelial cells. (ahajournals.org)
  • Incubation of human aortic endothelial cells with ALA activated AMPK and protected cells from linoleic acid-induced apoptosis. (ahajournals.org)
  • ALA improves vascular dysfunction by normalizing lipid metabolism and activating AMPK in endothelial cells. (ahajournals.org)
  • 5,6 We showed in rodents recently that chronic ALA treatment significantly reduced body weight gain primarily by decreasing food intake, and that this effect was mediated by the effect of ALA to decrease AMP-activated protein kinase (AMPK) activity in the hypothalamus. (ahajournals.org)
  • 8,9 When activated, AMPK increases glucose uptake and fatty acid oxidation 8,9 and decreases lipid accumulation in the tissues. (ahajournals.org)
  • 10 In contrast to the effect of ALA to inhibit AMPK in the hypothalamus, ALA activated AMPK in skeletal muscle, resulting in enhanced fatty acid oxidation and reduced lipid accumulation. (ahajournals.org)
  • Because LKB1 activates AMP-activated protein kinase (AMPK), which can negatively regulate mTOR, AMPK activation might be desirable for cancer therapy. (aacrjournals.org)
  • However, no known compounds activate AMPK independently of LKB1 in vivo , and the usefulness of activating AMPK in LKB1-mutant cancers is unknown. (aacrjournals.org)
  • Here, we show that lipid-based Akt inhibitors, phosphatidylinositol ether lipid analogues (PIA), activate AMPK independently of LKB1. (aacrjournals.org)
  • PIAs activated AMPK in LKB1-mutant non-small cell lung cancer (NSCLC) cell lines with similar concentration dependence as that required to inhibit Akt. (aacrjournals.org)
  • To assess whether another kinase capable of activating AMPK, CaMKKβ, contributed to PIA-induced AMPK activation, we used an inhibitor of CaMKK, STO-609. (aacrjournals.org)
  • Treatment of LKB1-mutant NSCLC xenografts with PIA decreased tumor volume by ∼50% and activated AMPK. (aacrjournals.org)
  • LKB1 activates AMP-activated protein kinase (AMPK) when the intracellular AMP/ATP ratio is increased ( 6 - 9 ). (aacrjournals.org)
  • AMPK is a heterotrimeric protein composed of α-catalytic, and β- and γ-regulatory subunits. (aacrjournals.org)
  • Conditions that deplete intracellular energy activate AMPK by direct binding of AMP to four tandem repeats of cystathionine-β synthase sequences located in the γ (regulatory) subunit ( 10 ). (aacrjournals.org)
  • The AMPK/mTOR signaling pathway was found to be activated in propofol-induced autophagosome accumulation. (medscimonit.com)
  • We found that dietary BBE ameliorates hyperglycemia and insulin sensitivity via activation of AMP-activated protein kinase (AMPK). (biomedsearch.com)
  • AMPK was activated in white adipose tissue (WAT), skeletal muscle, and the liver of diabetic mice fed BBE. (biomedsearch.com)
  • The AMP-activated protein kinase (AMPK) cascade is a sensor of cellular energy status. (biologists.org)
  • AMP activates the system by binding to two tandem domains on the γ subunits of AMPK, and this is antagonized by high concentrations of ATP. (biologists.org)
  • AMP binding causes activation by a sensitive mechanism involving phosphorylation of AMPK by the tumour suppressor LKB1. (biologists.org)
  • Once activated, AMPK switches on catabolic pathways that generate ATP while switching off ATP-consuming processes. (biologists.org)
  • The LKB1→AMPK→TSC2 pathway negatively regulates the target of rapamycin (TOR), and this appears to be responsible for limiting protein synthesis and cell growth, and protecting against apoptosis, during cellular stresses such as glucose starvation. (biologists.org)
  • In mammalian cells, it has recently become clear that the AMP-activated protein kinase (AMPK) system plays a crucial role. (biologists.org)
  • ADP is converted into AMP by adenylate kinase and this, combined with the fall in ATP, will activate AMPK. (biologists.org)
  • In the present study, we show that activation of AMP-activated protein kinase (AMPK) using A769662 led to a concomitant induction of EMT in multiple cancer cell types, as observed by enhanced expression of mesenchymal markers, decrease in epithelial markers, and increase in migration and invasion. (biologists.org)
  • AMP-activated protein kinase (AMPK) is an evolutionarily conserved stress-sensing kinase that becomes activated under a variety of stresses, including hypoxia, ischemia and nutrient deprivation, leading to a change in the ATP:AMP ratio ( Steinberg and Kemp, 2009 ). (biologists.org)
  • AMPK is the downstream component of a protein kinase cascade important in the regulation of cellular and whole body metabolism. (gla.ac.uk)
  • In addition, the present investigation demonstrates that the upstream AMPK kinase CaMKK is responsible for these VEGF-mediated effects. (gla.ac.uk)
  • While AMPK was necessary for VEGF-stimulated endothelial cell proliferation direct activation of the kinase was insufficient to induce this process. (gla.ac.uk)
  • The AMP-activated protein kinase (AMPK), consisting of catalytic alpha subunit and regulatory subunits beta and gamma, has a pivotal function in energy homoeostasis. (thebiogrid.org)
  • The energy sensor AMP-activated protein kinase (AMPK) signals neuronal death in glaucoma through inhibition of the mammalian target of rapamycin (mTOR). (arvojournals.org)
  • The AMP-activated protein kinase (AMPK) is a key intracellular energy sensor that is activated when endogenous ATP levels decline and AMP increases, as in nutrient deprivation and hypoxia. (arvojournals.org)
  • Active AMPK inhibits the mammalian target of rapamycin (mTOR), a key regulator of cell growth and protein synthesis. (arvojournals.org)
  • Subtraction hybridization after the exposure of keratinocytes to ultraviolet radiation identified a differentially expressed cDNA that encodes a protein of 630 amino acid residues possessing significant similarity to the catalytic domain of the sucrose-non-fermenting protein kinase (SNF1)/AMP-activated protein kinase (AMPK) family of serine/threonine protein kinases. (mcw.edu)
  • Northern blotting and reverse-transcriptase-mediated PCR demonstrated that mRNA transcripts for the SNF1/AMPK-related kinase (SNARK) were widely expressed in rodent tissues. (mcw.edu)
  • SNARK activity was significantly increased by AMP and 5-amino-4-imidazolecarboxamide riboside (AICAriboside) in rat keratinocyte cells, implying that SNARK might be activated by an AMPK kinase-dependent pathway. (mcw.edu)
  • We have been investigating the relationship between the activation of hypoxia-inducible factor 1 (HIF-1), the primary transcriptional regulator of the mammalian response to hypoxia, and 5′-AMP-activated protein kinase (AMPK), another regulatory system important for controlling cellular energy metabolism. (asm.org)
  • In the present study, we used mouse embryo fibroblasts nullizygous for HIF-1α or AMPK expression to show that AMPK is rapidly activated in vitro by both physiological and pathophysiological low-oxygen conditions, independently of HIF-1 activity. (asm.org)
  • Finally, we used transformed derivatives of wild-type and HIF-1α- or AMPKα-null mouse embryo fibroblasts to determine whether AMPK is activated in vivo. (asm.org)
  • We obtained evidence that AMPK is activated in authentic hypoxic tumor microenvironments and that this activity overlaps with regions of hypoxia detected by a chemical probe. (asm.org)
  • While exploring cellular mechanisms of ATP regulation, we observed that 5′-AMP-activated protein kinase (AMPK) activity was induced in both cell types, particularly under conditions of hypoxia and glucose deprivation. (asm.org)
  • AMPK activity is defined by a class of evolutionarily conserved serine/threonine kinases that are sensitive to various environmental stresses, especially those that perturb cellular energy status (reviewed in references 9 , 19 , and 47 ). (asm.org)
  • In terms of a role in ATP regulation, decreased cellular ATP levels promote AMPK activation through the allosteric binding of AMP, which in effect enables AMPK to sense increases in the cellular [AMP]/[ATP] ratio. (asm.org)
  • Rationale: The AMP-activated protein kinase (AMPK) is stimulated by hypoxia, and although the AMPK alpha 1 catalytic subunit has been implicated in angiogenesis, little is known about the role played by the AMPK alpha 2 subunit in vascular repair. (uni-muenchen.de)
  • Indeed, apoptosis was increased in hypoxic neutrophils from AMPK alpha 2(Delta MC) mice, fewer monocytes were recruited, and gene array analysis revealed attenuated expression of proangiogenic proteins in ischemic AMPK alpha 2(Delta MC) hindlimbs. (uni-muenchen.de)
  • Also, fewer proteins were regulated by hypoxia in neutrophils from AMPK alpha 2(Delta MC) mice. (uni-muenchen.de)
  • Variation in genes coding for AMP-activated protein kinase (AMPK) and breast cancer risk in the European Prospective Investigation on Cancer (EPIC). (diva-portal.org)
  • AMP-activated protein kinase (AMPK) is an energy sensing/signalling intracellular protein which is activated by an increase in the cellular AMP:ATP ratio after ATP depletion. (diva-portal.org)
  • Once activated, AMPK inhibits fatty acid synthesis and the Akt-mTOR pathway, and activates the p53-p21 axis. (diva-portal.org)
  • The AMP-activated protein kinase (AMPK) system acts as a sensor of cellular energy status that is conserved in all eukaryotic cells. (semanticscholar.org)
  • The AMPK (AMP-activated protein kinase)-related kinases MARK (microtubule-associated protein-regulating kinase/microtubule affinity-regulating kinase) and BRSK (brain-specific kinase) have been implicated in tau phosphorylation, but are insensitive to activation by cellular stress. (biochemj.org)
  • In primary mouse cortical neurons, CaMKKβ (Ca 2+ /calmodulin-dependent protein kinase kinase β) activation of AMPK in response to Aβ (amyloid-β peptide)-(1-42) leads to increased phosphorylation of tau at Ser 262 /Ser 356 and Ser 396 . (biochemj.org)
  • These findings identify a pathway in which Aβ-(1-42) activates CaMKKβ and AMPK via the NMDA receptor, suggesting the possibility that AMPK plays a role in the pathophysiological phosphorylation of tau. (biochemj.org)
  • The aim of this study was to investigate if (1) macrophage AMP-activated kinase (AMPK) regulates cellular CHOP accumulation and (2) whole-body Ampk deletion leads to neointimal disruption. (ahajournals.org)
  • In isolated or cultured macrophages, Ampkα1 deletion markedly increased apoptosis and CHOP, whereas pharmacological activation of AMPK dramatically reduced CHOP protein level via promoting CHOP degradation by proteasome. (ahajournals.org)
  • Insulin-stimulated glucose uptake is increased in white but not red muscle of insulin-resistant high-fat-fed (HF) rats after administration of the AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR). (garvan.org.au)
  • Previously, we and others showed that laforin and malin form a functional complex that regulates multiple aspects of glycogen metabolism, and that the interaction between laforin and malin is enhanced by conditions activating AMPK (AMP-activated protein kinase). (biochemj.org)
  • AMP-activated protein kinase (AMPK) plays an important role in controlling energy homeostasis and is envisioned as a promising target to treat metabolic disorders. (inserm.fr)
  • In the heart, AMPK is involved in short-term regulation and in transcriptional control of proteins involved in energy metabolism. (inserm.fr)
  • The AMP-activated protein kinase (AMPK) is a metabolic stress-sensing αβγ heterotrimer responsible for energy homeostasis. (monash.edu)
  • The expression levels of LC3-II, an autophagy-related protein, and AMP-activated protein kinase (AMPK), an autophagy inducer, were reduced in the cells infected with WT WNV, while the reduction was not observed in the cells infected with WNV with the mutations in C protein. (prolekare.cz)
  • In the cells expressing C protein, AMPK was co-precipitated with C protein and mutations in L51 and A52 reduced the interaction. (prolekare.cz)
  • Taken together, ubiquitination and degradation of AMPK by C protein resulted in the inhibition of autophagy and the accumulation of protein aggregates, which contributes to the development of neurological disease. (prolekare.cz)
  • In addition, we will quantify AMPK activity in fat cell lysates from the same patients to clarify whether metformin regulates this kinase in adipocytes. (isrctn.com)
  • AMP -activated protein kinase or AMPK is an enzyme that plays a role in cellular energy homeostasis. (diff.org)
  • AMPK is a heterotrimeric protein complex that is formed by α, β, and γ subunits. (diff.org)
  • The crystal structure of mammalian AMPK regulatory core domain (α C terminal, β C terminal, γ) has been solved in complex with AMP, ADP or ATP. (diff.org)
  • Furthermore, we demonstrate that signaling through the mitogen-activated protein kinase kinase (MEK)→extracellular signal-regulated kinase 1/2 (ERK1/2) cascade plays a crucial role in controlling the proper localization of AMPK. (diff.org)
  • The Role of 5-AMP-Activated Protein Kinase (AMPK) in Diabetic Nephropathy: A New Direction? (eurekaselect.com)
  • The AMP-activated protein kinase (AMPK) is a heterotrimeric protein that serves as an energy regulator for the cell. (eurekaselect.com)
  • K. Wyatt McMahon, Dora I. Zanescu, Vineeta Sood, Elmus G. Beale and Sharma S. Prabhakar, " The Role of 5-AMP-Activated Protein Kinase (AMPK) in Diabetic Nephropathy: A New Direction? (eurekaselect.com)
  • The glycogen-binding domain may target AMPK to glycogen so that other factors like glycogen-bound debranching enzyme or protein phosphatases can directly affect AMPK activity. (sdsc.edu)
  • 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. (sdsc.edu)
  • 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. (sdsc.edu)
  • Site 3 (AMP, ADP or ATP 2) is the weakest nucleotide-binding site on the gamma subunit, yet it is exquisitely sensitive to changes in nucleotide levels and this allows AMPK to respond rapidly to changes in cellular energy status. (sdsc.edu)
  • The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). (nih.gov)
  • 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. (nih.gov)
  • Furthermore, TMZ-induced enhancement of autophagy could be related to increased AMP-activated protein kinase (AMPK) phosphorylation and decreased Mammalian target of rapamycin (mTOR) phosphorylation, which was abolished by an AMPK-specific inhibitor (com C). Our data provide evidence that TMZ pretreatment protects against H/R injury by promoting autophagic flux through the AMPK signaling pathway. (ovid.com)
  • AMP-activated protein kinase (AMPK) is an attractive therapeutic target for managing metabolic diseases. (northwestern.edu)
  • A class of pharmacological activators, including Merck 991, binds the AMPK ADaM site, which forms the interaction surface between the kinase domain (KD) of the -subunit and the carbohydrate-binding module (CBM) of the -subunit. (northwestern.edu)
  • Here, we report the development of two new 991-derivative compounds, R734 and R739, which potently activate AMPK in a variety of cell types, including 2 -specific skeletal muscle cells. (northwestern.edu)
  • This mode of activation is reminiscent of that of ADP, which activates AMPK by binding to the nucleotide-binding sites in the -subunit, more than 60 Å away from the ADaM site. (northwestern.edu)
  • These structures and associated analyses identified a novel conformational state of the AMPK autoinhibitory domain associated with partial kinase activity and provide new insights into phosphorylation-dependent activation loop stabilization in AMPK. (northwestern.edu)
  • AMP-activated protein kinase (AMPK) activity has been found decreased in visceral adipose tissue of insulin-resistant patients. (biomedcentral.com)
  • Abstract In the present study, we have examined the potential ability of 5′-AMP-activated protein kinase (AMPK) to modulate NADPH oxidase activity in human neutrophils. (cf.ac.uk)
  • AMPK activated with either 5′-aminoimidazole-4-carboxamide ribonucleoside (AICAR) or with 5′-AMP significantly attenuated both phorbol 12-myristate 13-acetate (PMA) and formyl methionyl leucyl phenylalanine-stimulated superoxide anion (O2−) release by human neutrophils, consistently with a reduced translocation to the cell membrane and phosphorylation of a cytosolic component of NADPH oxidase, namely p47phox. (cf.ac.uk)
  • Present data demonstrate for the first time that the activation of AMPK, in states of low cellular energy charge (such as under high levels of 5′-AMP) or other signals, could be a factor contributing to reduce the host defense mechanisms. (cf.ac.uk)
  • The additive increase of mitochondrial markers observed in the white quadriceps may be explained by a combined effect of two separate mechanisms: high fat diet-induced post transcriptional increase in PGC-α protein and AMPK mediated increase in PGC-α protein via a transcriptional mechanism. (byu.edu)
  • Elevated AMP activates AMP-activated protein kinase (AMPK). (marquette.edu)
  • Normal and pathological stressors engage the AMP-activated protein kinase (AMPK) signaling axis to protect the cell from energetic pressures. (tdl.org)
  • AMP-activated protein kinase (AMPK) is induced by the exhaustion of cellular energy and activates adaptive alterations in cellular metabolism, which is the basis for cell survival during different environmental stresses. (usda.gov)
  • AMP-activated protein kinase (AMPK) is a heterotrimeric protein composed of a catalytic alpha subunit, a noncatalytic beta subunit, and a noncatalytic regulatory gamma subunit. (nih.gov)
  • The authors found that the gene encoding the gamma2 subunit of AMP-activated protein kinase (AMPK) strongly correlated with Zaire Ebolavirus transduction in the tumor cell panel. (nih.gov)
  • Activation of AMP-activated kinase (AMPK) in skeletal muscle increases glucose uptake, fatty acid oxidation, and mitochondrial biogenesis by increasing gene expression in these pathways. (qxmd.com)
  • Using primary muscle cells and mice deficient in PGC-1alpha, we found that the effects of AMPK on gene expression of glucose transporter 4, mitochondrial genes, and PGC-1alpha itself are almost entirely dependent on the function of PGC-1alpha protein. (qxmd.com)
  • Metformin increases the PGC-1alpha protein and oxidative enzyme activities possibly via AMPK phosphorylation in skeletal muscle in vivo. (qxmd.com)
  • Essential to activation of AMPK is its phosphorylation at Thr-172 by an upstream kinase, AMPKK, whose identity in mammalian cells has remained elusive. (pnas.org)
  • Here we present biochemical and genetic evidence indicating that the LKB1 serine/threonine kinase, the gene inactivated in the Peutz-Jeghers familial cancer syndrome, is the dominant regulator of AMPK activation in several mammalian cell types. (pnas.org)
  • We show that LKB1 directly phosphorylates Thr-172 of AMPKα in vitro and activates its kinase activity. (pnas.org)
  • LKB1-deficient murine embryonic fibroblasts show nearly complete loss of Thr-172 phosphorylation and downstream AMPK signaling in response to a variety of stimuli that activate AMPK. (pnas.org)
  • Reintroduction of WT, but not kinase-dead, LKB1 into these cells restores AMPK activity. (pnas.org)
  • AMP-activated protein kinase (AMPK) is the primary regulator of the cellular response to lowered ATP levels in eukaryotic cells ( 1 , 2 ). (pnas.org)
  • AMPK is activated by stimuli that include pathological stresses, such as oxidative damage, osmotic shock, hypoxia, and glucose deprivation, as well as physiological stimuli, such as exercise, muscle contraction, and hormones including leptin and adiponectin ( 1 ). (pnas.org)
  • AMPK exists in cells as a heterotrimeric complex composed of a catalytic kinase subunit (α) and two regulatory subunits (β and γ). (pnas.org)
  • AMP binding has been proposed to induce a conformational change in the heterotrimeric AMPK that allows it to serve as a better substrate for an upstream activating kinase(s). (pnas.org)
  • Phosphorylation of a single invariant threonine residue in the activation loop of the catalytic subunit (Thr-172 in human AMPKα1) has been shown to be required to activate all known AMPK homologues ( 1 ). (pnas.org)
  • A number of laboratories have reported biochemical purification of a kinase activity, AMPK kinase (AMPKK), that is capable of phosphorylating Thr-172 ( 6 - 8 ). (pnas.org)
  • One of those signaling pathways involves a protein called AMP-activated protein kinase (AMPK), a type of protein that modifies and regulates the function of other proteins. (alz.org)
  • Potent reversible AMP-activated protein kinase (AMPK) activator (EC 50 = 0.8 µM). (hellobio.com)
  • Activates AMPK allosterically and inhibits AMPK dephosphorylation. (hellobio.com)
  • Burnett PE, Barrow RK, Cohen NA, Snyder SH, Sabatini DM (1998) RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1. (springer.com)
  • Dennis PB, Pullen N, Kozma SC, Thomas G (1996) The principal rapamycin-sensitive p70(s6 k) phosphorylation sites, T-229 and T-389, are differentially regulated by rapamycin-insensitive kinase kinases. (springer.com)
  • Absence of this inhibitory region renders the protein independent of AMP but still requires phosphorylation of the activation loop (Crute et al. (atlasgeneticsoncology.org)
  • The activation of arginase was preceded by a transient increase in intracellular cAMP, tyrosine kinase phosphorylation, and p38 mitogen-activated protein kinase (MAPK) activation. (jimmunol.org)
  • Binding of AMP results in allosteric activation, inducing phosphorylation on Thr-172 of the AMPKa regulatory subunit (PRKAA) by LKB1 in complex with STE20-related adapter-alpha (STRAD alpha). (atlasgeneticsoncology.org)
  • The protein kinase Akt/PKB is stimulated by the phosphorylation of two regulatory residues, Thr 309 of the activation segment and Ser 474 of the hydrophobic motif (HM), that are structurally and functionally conserved within the AGC kinase family. (rcsb.org)
  • The activated state of the kinase was generated by phosphorylating Thr 309 using PDK1 and mimicking Ser 474 phosphorylation either with the S474D substitution or by replacing the HM of PKB with that of PIFtide, a potent mimic of a phosphorylated HM. (rcsb.org)
  • Comparison with the inactive PKB structure indicates that the role of Ser 474 phosphorylation is to promote the engagement of the HM with the N-lobe of the kinase domain, promoting a disorder-to-order transition of the alphaC helix. (rcsb.org)
  • Similar to protein phosphorylation, O-linked β-N-acetylglucosamine (O-GlcNAc) addition on Ser/Thr residues is a dynamic PTM that regulates many cellular processes including stress response ( 3 , 4 ), transcriptional activity ( 5 , 6 ), and epigenetic regulation ( 7 ). (frontiersin.org)
  • Alleviation of this intrinsic inhibition by interaction with the γ subunit is required for kinase activation, as is the phosphorylation of the α-subunit on Thr172 (reviewed elsewhere 2 ). (ahajournals.org)
  • Levels of phosphorylated mammalian target of rapamycin (mTOR) decreased with increasing DER, and down-regulation of mTOR activity was verified by a decrease in the phosphorylation state of two mTOR targets, 70-kDa ribosomal protein S6 kinase (p70S6K) and eukaryote initiation factor 4E binding protein 1 (4E-BP1). (aacrjournals.org)
  • Coincident with changes in mTOR phosphorylation, levels of activated protein kinase B (Akt) were also reduced. (aacrjournals.org)
  • Although AMP binding does not seem to directly promote LKB1 phosphorylation of T172 in the activation loop, it blocks dephosphorylation and inactivation by phosphatase PP2C ( 11 ). (aacrjournals.org)
  • Activation in response to increases in AMP involves phosphorylation by an upstream kinase, the tumor suppressor LKB1. (semanticscholar.org)
  • 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside and metformin inhibit hepatic glucose phosphorylation by an AMP-activated protein kinase-independent effect on glucokinase translocation. (semanticscholar.org)
  • Insulin antagonizes ischemia-induced Thr172 phosphorylation of AMP-activated protein kinase alpha-subunits in heart via hierarchical phosphorylation of Ser485/491. (semanticscholar.org)
  • Both kinases are activated by phosphorylation on a threonine residue within the activation loop segment of the catalytic subunit. (semanticscholar.org)
  • Effect of dietary [alpha]-lipoic acid on growth, body composition, muscle pH, and AMP-activated protein kinase phosphorylation in mice. (usda.gov)
  • Furthermore, AICAR also strongly reduced PMA-dependent H2O2 release, and induced the phosphorylation of c-jun N-terminal kinase 1 (p46), p38 mitogen-activated protein kinase and extracellular signal-regulated kinase. (cf.ac.uk)
  • The β subunit regulates the subcellular localization of the kinase ( 17 ) and mediates interactions with downstream targets ( 18 ). (pnas.org)
  • The kinases are heterotrimers that comprise a catalytic subunit and regulatory subunits that sense cellular energy levels. (nih.gov)
  • failed verification] As AMP binds both Bateman domains the γ subunit undergoes a conformational change which exposes the catalytic domain found on the α subunit. (wikipedia.org)
  • 5'-AMP-activated protein kinase catalytic subunit alpha-1 is an enzyme that in humans is encoded by the PRKAA1 gene. (wikipedia.org)
  • ATP and AMP bind competitively to a single site in the γ subunit, with their respective phosphate groups positioned near function-impairing mutants. (sciencemag.org)
  • both AMP and ATP bind in a mutually exclusive manner to the Bateman (CBS) domains of the gamma subunit. (wikipathways.org)
  • 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. (bl.uk)
  • The AMPKbeta subunit is the mammalian homolog of the S. cerevisiae Sip1p/Sip2p/Gal83p family of proteins that interact with the AMPKa homolog, Snf1p, and are involved in glucose regulation of gene expression. (atlasgeneticsoncology.org)
  • Mutations at the PRAAG2 (encoding the gamma2 subunit of AMP-activated protein kinase) causes glycogen overload, Wolff-Parkinson-White syndrome, arrhythmias, and heart failure. (atlasgeneticsoncology.org)
  • In its inactivated, nonphosphorylated state the kinase domain within the catalytic α subunit interacts with an autoinhibitory region in the same subunit. (ahajournals.org)
  • Site 3 is likely to be responsible for protection of a conserved threonine in the activation loop of the alpha catalytic subunit through conformational changes induced by binding of AMP or ADP. (sdsc.edu)
  • Two C-terminal cyclic nucleotide binding (CNB) domains cooperatively bind two molecules of cAMP, resulting in a conformational change of the R subunit that releases the active catalytic kinase subunit(s) from the inhibitory pseudo-substrate or substrate site of PKAR. (nature.com)
  • Because of the presence of cystathionine β synthase (CBS) domains, which can act as nucleoside-binding motifs in other proteins, as well as naturally occurring activating mutations, the γ subunit has been proposed to mediate direct binding of AMP ( 1 ). (pnas.org)
  • The protein encoded by this gene belongs to the serine/threonine protein kinase family. (wikipedia.org)
  • The N-terminal kinase domain carries out the serine/threonine kinase function. (atlasgeneticsoncology.org)
  • In this context, a previous study has identified phosphatidylinositol-3,4,5-bisphosphate (PIP 3 ), the product of phosphatidylinositol 3-kinases (PI3Ks), and PIM serine kinases as important regulators of T lymphocyte metabolism ( 18 ). (rupress.org)
  • LKB1 , or serine/threonine kinase 11 (STK11), is a tumor suppressor gene located on the short arm of chromosome 19 ( 1 ). (aacrjournals.org)
  • TSC2 is also regulated by the serine/threonine kinase Akt, which phosphorylates TSC2 at T1462, leading to its inactivation ( 15 ). (aacrjournals.org)
  • These direct phosphorylations of the PGC-1alpha protein at threonine-177 and serine-538 are required for the PGC-1alpha-dependent induction of the PGC-1alpha promoter. (qxmd.com)
  • The LKB1 serine/threonine kinase is a divergent yet evolutionarily well conserved kinase that most closely resembles CAMKK in its catalytic domain. (pnas.org)
  • It is well established that a high cAMP level is required to maintain prophase I arrest, whereas mitogen activated protein kinase (MAPK) activity is needed for later metaphase II arrest of the oocyte. (marquette.edu)
  • LKB1 and AMP-activated protein kinase control of mTOR signalling and growth. (wikipathways.org)
  • On the basis of these results, we propose a model to explain the apparent paradox that LKB1 is a tumor suppressor, yet cells lacking LKB1 are resistant to cell transformation by conventional oncogenes and are sensitive to killing in response to agents that elevate AMP. (pnas.org)
  • When energy status is compromised, the system activates catabolic pathways and switches off protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. (nih.gov)
  • It does so by inhibiting anabolic processes and by activating pathways producing ATP. (portlandpress.com)
  • Its activation under energetic stress is known to activate energy-producing pathways and to inactivate energy-consuming pathways, promoting ATP preservation and cell survival. (frontiersin.org)
  • In this study, we tested the hypothesis that DER exerts effects on intracellular energy sensing pathways, resulting in alterations of phosphorylated proteins that play a key role in the regulation of cancer. (aacrjournals.org)
  • All three kinases phosphorylate recombinant Snf1p on the activation-loop threonine. (pnas.org)
  • 5' AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle. (diabetesjournals.org)
  • Activation of AMP-activated protein kinase reduces hyperglycemia-induced mitochondrial reactive oxygen species production and promotes mitochondrial biogenesis in human umbilical vein endothelial cells," Diabetes , vol. 55, no. 1, pp. 120-127, 2006. (hindawi.com)
  • Endothelium-selective activation of AMP-activated protein kinase prevents diabetes mellitus-induced impairment in vascular function and reendothelialization via induction of heme oxygenase-1 in mice," Circulation , vol. 126, no. 10, pp. 1267-1277, 2012. (hindawi.com)
  • Recently, it has been demonstrated that LPS can directly bind to and activate caspase-11 when LPS is released into the cytosol from engulfed bacteria via as-yet-unrecognized routes or by artificial transfection into the cytosol ( 4 ), which subsequently leads to the non-classical NLRP3 inflammasome activation ( 3 , 5 ). (frontiersin.org)
  • The alphaC helix, by interacting with pThr 309, restructures and orders the activation segment, generating an active kinase conformation. (rcsb.org)
  • In the present study, Lai et al conclude that activation of sirtuin-3 (SIRT3) and AMP-activated protein kinase in skeletal muscle is crucial for the observed effects associated with nitrate and nitrite treatment. (ahajournals.org)
  • In our opinion, this could rather suggest that the effect of inorganic nitrite on SIRT3 and AMP-activated protein kinase activation is due to attenuation of oxidative stress, which is in agreement with recently published studies. (ahajournals.org)
  • 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. (biochemsoctrans.org)
  • Dietary anthocyanin-rich bilberry extract ameliorates hyperglycemia and insulin sensitivity via activation of AMP-activated protein kinase in diabetic mice. (biomedsearch.com)
  • The mechanisms of metformin action have yet to be fully elucidated, although recent data have implicated AMP-kinase activation as a potential mediator of metformin action in hepatocytes and skeletal myocytes. (isrctn.com)
  • Surprisingly, we found that they have only minor effects on direct kinase activity of the recombinant 121 isoform yet robustly enhance protection against activation loop dephosphorylation. (northwestern.edu)
  • cAMP declines during meiotic resumption by the activation of phosphodiesterase (PDE), which converts cAMP into AMP. (marquette.edu)
  • In certain cell types, Thr172 can be phosphorylated by calmodulin-dependent protein kinase kinases (CAmKK), in turn activated by calcium. (wikipathways.org)
  • Calcium/calmodulin-dependent protein kinase kinase (CAMKK) has been demonstrated to serve as a surrogate AMPKK in vitro , although some of its biochemical properties suggest it may not be a bona fide AMPKK in vivo ( 9 ). (pnas.org)
  • Lawrence JC Jr (2001) mTOR-dependent control of skeletal muscle protein synthesis. (springer.com)
  • mTOR is a bona fide target in cancer treatment and prevention because it regulates cellular growth and protein synthesis through downstream targets such as 4E-BP1, S6K, and S6 (reviewed in ref. 16 ). (aacrjournals.org)
  • Results showed that IL-13 increased arginase activity through de novo synthesis of the arginase I mRNA and protein. (jimmunol.org)
  • The dynamics of adenylate kinase-catalyzed phosphotransfer regulates multiple intracellular and extracellular energy-dependent and nucleotide signaling processes, including excitation-contraction coupling, hormone secretion, cell and ciliary motility, nuclear transport, energetics of cell cycle, DNA synthesis and repair, and developmental programming. (mdpi.com)
  • The signals that control Snf1 activity in response to glucose levels are not understood, although the AMP:ATP ratio may have a role under some conditions ( 11 ). (pnas.org)
  • The kinase is activated in response to stresses that deplete cellular ATP supplies such as low glucose, hypoxia, ischemia and heat shock. (wikipathways.org)
  • 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. (biochemsoctrans.org)
  • 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. (biochemsoctrans.org)
  • Together, these findings suggest that enhanced glucose absorption and/or glycolytic activity mediated by HIF-1 in response to hypoxia activates c-Jun/AP-1, as well as other targets of c-Jun N-terminal kinases. (asm.org)
  • 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). (semanticscholar.org)
  • The SNF1 protein kinase complex plays an essential role in regulating gene expression in response to the level of extracellular glucose in budding yeast. (semanticscholar.org)
  • AMP-activated protein kinase, super metabolic regulator. (nih.gov)
  • these are typically energy metabolic enzymes and proteins involved in transcriptional regulation. (springer.com)
  • 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)
  • 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 concept of improved AMP-activated protein kinase signaling by the nitrate-nitrite-NO pathway supports recent studies in rat vascular smooth muscle cells and isolated rat hearts 3 and in mouse liver in a model of the metabolic syndrome. (ahajournals.org)
  • δ-Opioid receptors stimulate the metabolic sensor AMP-activated protein kinase through coincident signaling with G(q/11)-coupled receptors. (semanticscholar.org)
  • Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. (sickkids.ca)
  • Adenylate kinase and downstream AMP signaling is an integrated metabolic monitoring system which reads the cellular energy state in order to tune and report signals to metabolic sensors. (mdpi.com)
  • A network of adenylate kinase isoforms (AK1-AK7) are distributed throughout intracellular compartments, interstitial space and body fluids to regulate energetic and metabolic signaling circuits, securing efficient cell energy economy, signal communication and stress response. (mdpi.com)
  • Metabolomic analyses indicate that cellular, interstitial and blood AMP levels are potential metabolic signals associated with vital functions including body energy sensing, sleep, hibernation and food intake. (mdpi.com)
  • Yeast SNF1 is functionally related to mammalian AMP-activated protein kinase and regulates acetyl-CoA carboxylase in vivo. (semanticscholar.org)
  • Whenever the cellular ATP:ADP ratio falls, owing to a stress that inhibits ATP production or increases ATP consumption, this is amplified by adenylate kinase into a much larger increase in the AMP:ATP ratio. (biologists.org)
  • Downregulation of AMP-activated protein kinase by Cidea-mediated ubiquitination and degradation in brown adipose tissue. (thebiogrid.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)
  • AMP-activated protein kinase and ATP-citrate lyase are two distinct molecular targets for ETC-1002, a novel small molecule regulator of lipid and carbohydrate metabolism. (sickkids.ca)
  • Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. (drugbank.com)
  • AID is required for allosteric regulation via AMP. (atlasgeneticsoncology.org)
  • Protein kinase A (PKA), the main effector of cAMP in eukaryotes, is a paradigm for the mechanisms of ligand-dependent and allosteric regulation in signalling. (nature.com)
  • 7500 members that confers ligand-dependent allosteric regulation to a diverse range of proteins 2 . (nature.com)
  • Translation inhibition during the induction of apoptosis: RNA or protein degradation? (portlandpress.com)
  • Isoflurane Protects Against Human Endothelial Cell Apoptosis by Inducing Sphingosine Kinase-1 via ER. (biomedsearch.com)
  • 2. Kobayashi S, Orba Y, Yamaguchi H, Kimura T, Sawa H. Accumulation of ubiquitinated proteins is related to West Nile virus-induced neuronal apoptosis. (prolekare.cz)
  • AMP-activated protein kinase and autophagy. (inserm.fr)
  • Ubiquitin accumulation in autophagy-deficient mice is dependent on the Nrf2-mediated stress response pathway: a potential role for protein aggregation in autophagic substrate selection. (prolekare.cz)
  • In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1. (drugbank.com)
  • Can inhibit the non-autophagy complex by phosphorylating PIK3C3 and can activate the pro-autophagy complex by phosphorylating BECN1 (By similarity). (drugbank.com)
  • In yeast, genetic approaches have failed to yield mutations in the cognate gene, suggesting that multiple kinases activate Snf1. (pnas.org)
  • p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence. (uniprot.org)
  • section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. (uniprot.org)
  • 1998). A UBA-like auto-inhibitory domain (AID) is present between the α-RIM sensor loop and the kinase domain. (atlasgeneticsoncology.org)
  • Beyond AICA riboside: in search of new specific AMP-activated protein kinase activators. (hellobio.com)
  • immunoprecipitated SNARK exhibited phosphotransferase activity with the synthetic peptide substrate HMRSAMSGLHLVKRR (SAMS) as a kinase substrate. (mcw.edu)
  • We have here identified three yeast kinases, Pak1p, Tos3p, and Elm1p, that activate Snf1 kinase in vivo . (pnas.org)
  • In the yeast Saccharomyces cerevisiae , the Snf1 kinase is also required for stress responses, notably the adaptation of cells to carbon stress. (pnas.org)
  • We have explored the possibility that Tos3p and Pak1p activate Snf1 kinase. (pnas.org)
  • We present evidence that Tos3p and Pak1p, together with a third closely related kinase, Elm1p, are required for Snf1 function in vivo and show that these three kinases phosphorylate and activate Snf1 in vitro . (pnas.org)
  • It belongs to a highly conserved eukaryotic protein family and its orthologues are SNF1 in yeast, and SnRK1 in plants. (wikipedia.org)
  • SNF1 shares structural and functional similarities with mammalian AMP-activated protein kinase. (semanticscholar.org)
  • It consists of three proteins (subunits) that together make a functional enzyme, conserved from yeast to humans. (wikipedia.org)
  • 1996). "Characterization of AMP-activated protein kinase beta and gamma subunits. (wikipedia.org)
  • the β subunits provide a structural link between the other subunits and also contain a specialized sequence that binds to glycogen, whereas the γ subunits contain the binding sites that enable AMP to activate the complex. (ahajournals.org)
  • Although the mammalian kinase is the only example that is well characterized at the biochemical level, genes encoding orthologues of the α, β and γ subunits are found in all eukaryotic species whose genome sequences have been determined. (biologists.org)
  • Snf4p stimulates kinase activity by counter-acting autoinhibition by the Snf1p regulatory domain ( 16 ). (pnas.org)
  • Together, these data demonstrate for the first time that IL-13 down-regulates NO production through arginase induction via cAMP/PKA, tyrosine kinase, and p38 MAPK signalings and underline the importance of arginase in the immunosuppressive activity of IL-13 in activated macrophages. (jimmunol.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)
  • In white quadriceps, there was a cumulative effect of treatments on LCAD, cytochrome c, and PGC-α protein, as well as on citrate synthase and β-HAD activity. (byu.edu)
  • Mitochondrial biogenesis and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) deacetylation by physical activity: intact adipocytokine signaling is required. (qxmd.com)
  • Interactions between ROS and AMP kinase activity in the regulation of PGC-1alpha transcription in skeletal muscle cells. (qxmd.com)
  • AMPKbeta1 protein expression is highest in the liver, and testis and low in kidney and skeletal muscle. (atlasgeneticsoncology.org)
  • alpha-Lipoic acid increases energy expenditure by enhancing adenosine monophosphate-activated protein kinase-peroxisome proliferator-activated receptor-gamma coactivator-1alpha signaling in the skeletal muscle of aged mice. (qxmd.com)
  • However, if the reaction catalysed by adenylate kinase (2ADP ↔ ATP + AMP) is maintained close to equilibrium (which appears to be the case in most eukaryotic cells), one can easily show that the AMP:ATP ratio varies as the square of the ADP:ATP ratio ( Hardie and Hawley, 2001 ). (biologists.org)
  • There are many transcriptional regulators, including PR domain-containing 16 (PRDM16), peroxisome proliferator-activated receptor-γ (PPARγ) coactivator 1α (PGC1α), CCAAT/enhancer-binding protein α and PPARγ, as well as various secreted mediators, such as bone morphogenetic protein 7, Irisin, fibroblast growth factor 21, atrial and brain natriuretic peptides, that can induce the formation of brown-like adipocytes. (nature.com)
  • The pro-inflammatory environment drives macrophage polarization towards the classically activated M1 state, and they tend to accumulate around necrotic adipocytes, forming crown-like structures. (clinsci.org)
  • Resveratrol significantly increased mRNA and/or protein expression of brown adipocyte markers, including uncoupling protein 1 (UCP1), PR domain-containing 16, cell death-inducing DFFA-like effector A, elongation of very long-chain fatty acids protein 3, peroxisome proliferator-activated receptor-γ coactivator 1α, cytochrome c and pyruvate dehydrogenase, in differentiated iWAT stromal vascular cells (SVCs), suggesting that resveratrol induced brown-like adipocyte formation in vitro . (nature.com)
  • 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)
  • EMT can be stimulated by a plethora of cues such as hypoxia, signaling through TGFβ, receptor tyrosine kinases, Notch and Wnt ( Polyak and Weinberg, 2009 ). (biologists.org)
  • AMP-activated protein kinase is required for exercise-induced peroxisome proliferator-activated receptor co-activator 1 translocation to subsarcolemmal mitochondria in skeletal muscle. (qxmd.com)
  • An exclusive from Hello Bio, Cmpd101 is a novel, potent, selective G-protein coupled receptor kinase 2 and 3 inhibitor. (hellobio.com)
  • PGC-1{alpha} is required for AICAR-induced expression of GLUT4 and mitochondrial proteins in mouse skeletal muscle. (qxmd.com)
  • Hence, the synonym cAMP-dependent protein kinase is commonly used. (nature.com)
  • Recently, mass spectrometric analysis of yeast protein complexes indicated that Tos3p (YGL179C) copurifies with Snf4p ( 22 ), and Pak1p (unrelated to p21-activated kinase) copurifies with Snf1p and with Snf4p ( 23 ). (pnas.org)
  • Inflammasomes are large multimeric protein complexes present in the cytosol of immune cells to sense and respond to pathogen infection or tissue injury. (frontiersin.org)
  • Boesenbergia pandurata Attenuates Diet-Induced Obesity by Activating AMP-Activated Protein Kinase and Regulating Lipid Metabolism. (biomedsearch.com)
  • Effects of high-fat diet and AMP-activated protein kinase modulation on the regulation of whole-body lipid metabolism. (umassmed.edu)
  • AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP. (sickkids.ca)
  • 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)
  • 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. (biochemsoctrans.org)
  • Binding of one AMP to a Bateman domain cooperatively increases the binding affinity of the second AMP to the other Bateman domain. (wikipedia.org)
  • AMP-activated protein kinase connects cellular energy metabolism to KATP channel function. (harvard.edu)
  • Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. (sickkids.ca)
  • The induction of arginase was abolished by a protein kinase A (PKA) inhibitor, KT5720, and was down-regulated by tyrosine kinase inhibitors and a p38 MAPK inhibitor, SB203580. (jimmunol.org)
  • Furthermore, the induction of arginase was insensitive to the protein kinase C and p44/p42 MAPK kinase inhibitors. (jimmunol.org)
  • Dufner A, Thomas G (1999) Ribosomal S6 kinase signaling and the control of translation. (springer.com)
  • The eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation. (sickkids.ca)
  • Expression of capsid (C) protein induced the accumulation, while mutations at residues L51 and A52 in C protein abrogated the accumulation. (prolekare.cz)
  • Although the viral replication was not affected, the accumulation of ubiquitinated proteins in brain and neurological symptoms were attenuated in the mouse inoculated with WNV with the mutations in C protein as compared with that with WT WNV. (prolekare.cz)
  • Reihill, J. , Ewart, M. , Hardie, D. and Salt, I. (2007) AMP-activated protein kinase mediates VEGF-stimulated endothelial NO production. (gla.ac.uk)