Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Protein Kinase C: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.Cyclic AMP-Dependent Protein Kinases: A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Calcium-Calmodulin-Dependent Protein Kinases: A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.Calcium-Calmodulin-Dependent Protein Kinase Type 2: A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Calcium-Calmodulin-Dependent Protein Kinase Type 1: A monomeric calcium-calmodulin-dependent protein kinase subtype that is expressed in a broad variety of mammalian cell types. Its expression is regulated by the action of CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE. Several isoforms of this enzyme subtype are encoded by distinct genes.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Cyclic GMP-Dependent Protein Kinases: A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Kinetics: The rate dynamics in chemical or physical systems.Mitogen-Activated Protein Kinases: A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).Paramecium tetraurelia: A species of ciliate protozoa. It is used in biomedical research.MAP Kinase Signaling System: An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.p38 Mitogen-Activated Protein Kinases: A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.Phosphatidylinositol 3-Kinases: Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Cell Line: Established cell cultures that have the potential to propagate indefinitely.eIF-2 Kinase: A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Cyclic GMP: Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Protein Kinase C-alpha: A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.Mitogen-Activated Protein Kinase 1: A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.Cyclic AMP-Dependent Protein Kinase Catalytic Subunits: Specific enzyme subunits that form the active sites of the type I and type II cyclic-AMP protein kinases. Each molecule of enzyme contains two catalytic subunits.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Cyclic AMP-Dependent Protein Kinase Type II: A cyclic AMP-dependent protein kinase subtype primarily found in particulate subcellular fractions. They are tetrameric proteins that contain two catalytic subunits and two type II-specific regulatory subunits.Mitogen-Activated Protein Kinase Kinases: A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.Nucleotides, CyclicMitogen-Activated Protein Kinase 3: A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.Protein Kinase C-delta: A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.Bucladesine: A cyclic nucleotide derivative that mimics the action of endogenous CYCLIC AMP and is capable of permeating the cell membrane. It has vasodilator properties and is used as a cardiac stimulant. (From Merck Index, 11th ed)Colforsin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.Isoquinolines: A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)Calcium-Binding Proteins: Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.JNK Mitogen-Activated Protein Kinases: A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Phosphoprotein Phosphatases: A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)-L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor.AMP-Activated Protein Kinases: Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Cyclic GMP-Dependent Protein Kinase Type I: A cyclic GMP-dependent protein kinase subtype that is expressed in SMOOTH MUSCLE tissues and plays a role in regulation of smooth muscle contraction. Two isoforms, PKGIalpha and PKGIbeta, of the type I protein kinase exist due to alternative splicing of its mRNA.1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine: A specific protein kinase C inhibitor, which inhibits superoxide release from human neutrophils (PMN) stimulated with phorbol myristate acetate or synthetic diacylglycerol.PhosphoproteinsSerine: 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.Cyclic AMP-Dependent Protein Kinase RIalpha Subunit: A type I cAMP-dependent protein kinase regulatory subunit that plays a role in confering CYCLIC AMP activation of protein kinase activity. It has a lower affinity for cAMP than the CYCLIC-AMP-DEPENDENT PROTEIN KINASE RIBETA SUBUNIT.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.8-Bromo Cyclic Adenosine Monophosphate: A long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase.Receptors, Cyclic AMP: Cell surface proteins that bind cyclic AMP with high affinity and trigger intracellular changes which influence the behavior of cells. The best characterized cyclic AMP receptors are those of the slime mold Dictyostelium discoideum. The transcription regulator CYCLIC AMP RECEPTOR PROTEIN of prokaryotes is not included nor are the eukaryotic cytoplasmic cyclic AMP receptor proteins which are the regulatory subunits of CYCLIC AMP-DEPENDENT PROTEIN KINASES.Protamine Kinase: An aspect of protein kinase (EC 2.7.1.37) in which serine residues in protamines and histones are phosphorylated in the presence of ATP.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Benzylamines: Toluenes in which one hydrogen of the methyl group is substituted by an amino group. Permitted are any substituents on the benzene ring or the amino group.Protein Kinase C-epsilon: A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.src-Family Kinases: A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.Protein Kinase C beta: PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.Calcium-Calmodulin-Dependent Protein Kinase Type 4: A monomeric calcium-calmodulin-dependent protein kinase subtype that is primarily expressed in neuronal tissues; T-LYMPHOCYTES and TESTIS. The activity of this enzyme is regulated by its phosphorylation by CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Cyclic GMP-Dependent Protein Kinase Type II: A cyclic GMP-dependent protein kinase subtype that is expressed predominantly in INTESTINES, BRAIN, and KIDNEY. The protein is myristoylated on its N-terminus which may play a role its membrane localization.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Molecular Weight: The sum of the weight of all the atoms in a molecule.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.CDC2 Protein Kinase: Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Sulfonamides: A group of compounds that contain the structure SO2NH2.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.1-Methyl-3-isobutylxanthine: A potent cyclic nucleotide phosphodiesterase inhibitor; due to this action, the compound increases cyclic AMP and cyclic GMP in tissue and thereby activates CYCLIC NUCLEOTIDE-REGULATED PROTEIN KINASESCell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Casein Kinase II: A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.Phosphatidylserines: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to a serine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and serine and 2 moles of fatty acids.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.MAP Kinase Kinase Kinases: Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).Calcium Signaling: Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.RNA, Double-Stranded: RNA consisting of two strands as opposed to the more prevalent single-stranded RNA. Most of the double-stranded segments are formed from transcription of DNA by intramolecular base-pairing of inverted complementary sequences separated by a single-stranded loop. Some double-stranded segments of RNA are normal in all organisms.Extracellular Signal-Regulated MAP Kinases: A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.3',5'-Cyclic-AMP Phosphodiesterases: Enzymes that catalyze the hydrolysis of CYCLIC AMP to form adenosine 5'-phosphate. The enzymes are widely distributed in animal tissue and control the level of intracellular cyclic AMP. Many specific enzymes classified under this heading demonstrate additional spcificity for 3',5'-cyclic IMP and CYCLIC GMP.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.p21-Activated Kinases: A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.Cyclic AMP Response Element-Binding Protein: A protein that has been shown to function as a calcium-regulated transcription factor as well as a substrate for depolarization-activated CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASES. This protein functions to integrate both calcium and cAMP signals.MAP Kinase Kinase 1: An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Proto-Oncogene Proteins c-akt: A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Magnesium: A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.Ribosomal Protein S6 Kinases: A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.Sirtuins: A homologous family of regulatory enzymes that are structurally related to the protein silent mating type information regulator 2 (Sir2) found in Saccharomyces cerevisiae. Sirtuins contain a central catalytic core region which binds NAD. Several of the sirtuins utilize NAD to deacetylate proteins such as HISTONES and are categorized as GROUP III HISTONE DEACETYLASES. Several other sirtuin members utilize NAD to transfer ADP-RIBOSE to proteins and are categorized as MONO ADP-RIBOSE TRANSFERASES, while a third group of sirtuins appears to have both deacetylase and ADP ribose transferase activities.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Plant Proteins: Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which VEGETABLE PROTEINS is available.Cyclic AMP Receptor Protein: A transcriptional regulator in prokaryotes which, when activated by binding cyclic AMP, acts at several promoters. Cyclic AMP receptor protein was originally identified as a catabolite gene activator protein. It was subsequently shown to regulate several functions unrelated to catabolism, and to be both a negative and a positive regulator of transcription. Cell surface cyclic AMP receptors are not included (CYCLIC AMP RECEPTORS), nor are the eukaryotic cytoplasmic cyclic AMP receptor proteins, which are the regulatory subunits of CYCLIC AMP-DEPENDENT PROTEIN KINASES.DiglyceridesDNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Phorbol 12,13-Dibutyrate: A phorbol ester found in CROTON OIL which, in addition to being a potent skin tumor promoter, is also an effective activator of calcium-activated, phospholipid-dependent protein kinase (protein kinase C). Due to its activation of this enzyme, phorbol 12,13-dibutyrate profoundly affects many different biological systems.Egtazic Acid: A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.Sirtuin 1: A sirtuin family member found primarily in the CELL NUCLEUS. It is an NAD-dependent deacetylase with specificity towards HISTONES and a variety of proteins involved in gene regulation.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.MAP Kinase Kinase 4: A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.Casein Kinases: A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.Theophylline: A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLYL CYCLASES and cyclic AMP.Cell Line, Tumor: A cell line derived from cultured tumor cells.Staurosporine: An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)Phorbol Esters: Tumor-promoting compounds obtained from CROTON OIL (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.Muscle, Smooth, Vascular: The nonstriated involuntary muscle tissue of blood vessels.MaleimidesIndoles: 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.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Isoproterenol: Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Pyruvate Kinase: ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.Swine: Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).Glycogen Synthase Kinase 3: A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.Phosphotransferases (Alcohol Group Acceptor): A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Creatine Kinase: A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.Arabidopsis Proteins: Proteins that originate from plants species belonging to the genus ARABIDOPSIS. The most intensely studied species of Arabidopsis, Arabidopsis thaliana, is commonly used in laboratory experiments.DNA-Activated Protein Kinase: A serine-threonine protein kinase that, when activated by DNA, phosphorylates several DNA-binding protein substrates including the TUMOR SUPPRESSOR PROTEIN P53 and a variety of TRANSCRIPTION FACTORS.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Adenosine Monophosphate: Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.Flavonoids: A group of phenyl benzopyrans named for having structures like FLAVONES.Hippocampus: A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.3-Phosphoinositide-Dependent Protein Kinases: Highly conserved protein-serine threonine kinases that phosphorylate and activate a group of AGC protein kinases, especially in response to the production of the SECOND MESSENGERS, phosphatidylinositol 3,4,-biphosphate (PtdIns(3,4)P2) and phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3).AMP Deaminase: An enzyme that catalyzes the deamination of AMP to IMP. EC 3.5.4.6.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.Arabidopsis: A plant genus of the family BRASSICACEAE that contains ARABIDOPSIS PROTEINS and MADS DOMAIN PROTEINS. The species A. thaliana is used for experiments in classical plant genetics as well as molecular genetic studies in plant physiology, biochemistry, and development.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Phosphodiesterase Inhibitors: Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.Mice, Inbred C57BLCell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Saccharomyces cerevisiae Proteins: Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.rho-Associated Kinases: A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.Androstadienes: Derivatives of the steroid androstane having two double bonds at any site in any of the rings.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.3T3 Cells: Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.Alkaloids: Organic nitrogenous bases. Many alkaloids of medical importance occur in the animal and vegetable kingdoms, and some have been synthesized. (Grant & Hackh's Chemical Dictionary, 5th ed)Imidazoles: Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).Subcellular Fractions: Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163)Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Cell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system.Phosphoserine: The phosphoric acid ester of serine.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Carbazoles: Benzo-indoles similar to CARBOLINES which are pyrido-indoles. In plants, carbazoles are derived from indole and form some of the INDOLE ALKALOIDS.Mitogen-Activated Protein Kinase 8: A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Precipitin Tests: Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.I-kappa B Kinase: A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Trifluoperazine: A phenothiazine with actions similar to CHLORPROMAZINE. It is used as an antipsychotic and an antiemetic.Thymidine Kinase: An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21.Calcimycin: An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems.Ribosomal Protein S6 Kinases, 90-kDa: A family of ribosomal protein S6 kinases that are structurally distinguished from RIBOSOMAL PROTEIN S6 KINASES, 70-KDA by their apparent molecular size and the fact they contain two functional kinase domains. Although considered RIBOSOMAL PROTEIN S6 KINASES, members of this family are activated via the MAP KINASE SIGNALING SYSTEM and have been shown to act on a diverse array of substrates that are involved in cellular regulation such as RIBOSOMAL PROTEIN S6 and CAMP RESPONSE ELEMENT-BINDING PROTEIN.Receptors, N-Methyl-D-Aspartate: A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.

Intracellular signalling: PDK1--a kinase at the hub of things. (1/7238)

Phosphoinositide-dependent kinase 1 (PDK1) is at the hub of many signalling pathways, activating PKB and PKC isoenzymes, as well as p70 S6 kinase and perhaps PKA. PDK1 action is determined by colocalization with substrate and by target site availability, features that may enable it to operate in both resting and stimulated cells.  (+info)

The MAP kinase ERK2 inhibits the cyclic AMP-specific phosphodiesterase HSPDE4D3 by phosphorylating it at Ser579. (2/7238)

The extracellular receptor stimulated kinase ERK2 (p42(MAPK))-phosphorylated human cAMP-specific phosphodiesterase PDE4D3 at Ser579 and profoundly reduced ( approximately 75%) its activity. These effects could be reversed by the action of protein phosphatase PP1. The inhibitory state of PDE4D3, engendered by ERK2 phosphorylation, was mimicked by the Ser579-->Asp mutant form of PDE4D3. In COS1 cells transfected to express PDE4D3, challenge with epidermal growth factor (EGF) caused the phosphorylation and inhibition of PDE4D3. This effect was blocked by the MEK inhibitor PD98059 and was not apparent using the Ser579-->Ala mutant form of PDE4D3. Challenge of HEK293 and F442A cells with EGF led to the PD98059-ablatable inhibition of endogenous PDE4D3 and PDE4D5 activities. EGF challenge of COS1 cells transfected to express PDE4D3 increased cAMP levels through a process ablated by PD98059. The activity of the Ser579-->Asp mutant form of PDE4D3 was increased by PKA phosphorylation. The transient form of the EGF-induced inhibition of PDE4D3 is thus suggested to be due to feedback regulation by PKA causing the ablation of the ERK2-induced inhibition of PDE4D3. We identify a novel means of cross-talk between the cAMP and ERK signalling pathways whereby cell stimuli that lead to ERK2 activation may modulate cAMP signalling.  (+info)

Phosphorylation of the DNA repair protein APE/REF-1 by CKII affects redox regulation of AP-1. (3/7238)

The DNA repair protein apurinic endonuclease (APE/Ref-1) exerts several physiological functions such as cleavage of apurinic/apyrimidinic sites and redox regulation of the transcription factor AP-1, whose activation is part of the cellular response to DNA damaging treatments. Here we demonstrate that APE/Ref-1 is phosphorylated by casein kinase II (CKII). This was shown for both the recombinant APE/Ref-1 protein (Km=0.55 mM) and for APE/Ref-1 expressed in COS cells. Phosphorylation of APE/Ref-1 did not alter the repair activity of the enzyme, whereas it stimulated its redox capability towards AP-1, thus promoting DNA binding activity of AP-1. Inhibition of CKII mediated phosphorylation of APE/Ref-1 blocked mutagen-stimulated increase in AP-1 binding. It also abrogated the induction of c-Jun protein and rendered cells more sensitive to induced DNA damage. Thus, phosphorylation of APE/Ref-1 appears to be involved in regulating the different physiological activities of the enzyme. CKII mediated phosphorylation of APE/Ref-1 and concomitant increase in AP-1 binding activity appears to be a novel mechanism of cellular stress response, forcing transcription of AP-1 target gene(s) the product(s) of which may exert protective function.  (+info)

A novel interaction mechanism accounting for different acylphosphatase effects on cardiac and fast twitch skeletal muscle sarcoplasmic reticulum calcium pumps. (4/7238)

In cardiac and skeletal muscle Ca2+ translocation from cytoplasm into sarcoplasmic reticulum (SR) is accomplished by different Ca2+-ATPases whose functioning involves the formation and decomposition of an acylphosphorylated phosphoenzyme intermediate (EP). In this study we found that acylphosphatase, an enzyme well represented in muscular tissues and which actively hydrolyzes EP, had different effects on heart (SERCA2a) and fast twitch skeletal muscle SR Ca2+-ATPase (SERCA1). With physiological acylphosphatase concentrations SERCA2a exhibited a parallel increase in the rates of both ATP hydrolysis and Ca2+ transport; in contrast, SERCA1 appeared to be uncoupled since the stimulation of ATP hydrolysis matched an inhibition of Ca2+ pump. These different effects probably depend on phospholamban, which is associated with SERCA2a but not SERCA1. Consistent with this view, the present study suggests that acylphosphatase-induced stimulation of SERCA2a, in addition to an enhanced EP hydrolysis, may be due to a displacement of phospholamban, thus to a removal of its inhibitory effect.  (+info)

PrKX is a novel catalytic subunit of the cAMP-dependent protein kinase regulated by the regulatory subunit type I. (5/7238)

The human X chromosome-encoded protein kinase X (PrKX) belongs to the family of cAMP-dependent protein kinases. The catalytically active recombinant enzyme expressed in COS cells phosphorylates the heptapeptide Kemptide (LRRASLG) with a specific activity of 1.5 micromol/(min.mg). Using surface plasmon resonance, high affinity interactions were demonstrated with the regulatory subunit type I (RIalpha) of cAMP-dependent protein kinase (KD = 10 nM) and the heat-stable protein kinase inhibitor (KD = 15 nM), but not with the type II regulatory subunit (RIIalpha, KD = 2.3 microM) under physiological conditions. Kemptide and autophosphorylation activities of PrKX are strongly inhibited by the RIalpha subunit and by protein kinase inhibitor in vitro, but only weakly by the RIIalpha subunit. The inhibition by the RIalpha subunit is reversed by addition of nanomolar concentrations of cAMP (Ka = 40 nM), thus demonstrating that PrKX is a novel, type I cAMP-dependent protein kinase that is activated at lower cAMP concentrations than the holoenzyme with the Calpha subunit of cAMP-dependent protein kinase. Microinjection data clearly indicate that the type I R subunit but not type II binds to PrKX in vivo, preventing the translocation of PrKX to the nucleus in the absence of cAMP. The RIIalpha subunit is an excellent substrate for PrKX and is phosphorylated in vitro in a cAMP-independent manner. We discuss how PrKX can modulate the cAMP-mediated signal transduction pathway by preferential binding to the RIalpha subunit and by phosphorylating the RIIalpha subunit in the absence of cAMP.  (+info)

Prior exposure to neurotrophins blocks inhibition of axonal regeneration by MAG and myelin via a cAMP-dependent mechanism. (6/7238)

MAG is a potent inhibitor of axonal regeneration. Here, inhibition by MAG, and myelin in general, is blocked if neurons are exposed to neurotrophins before encountering the inhibitor; priming cerebellar neurons with BDNF or GDNF, but not NGF, or priming DRG neurons with any of these neurotrophins blocks inhibition by MAG/myelin. Dibutyryl cAMP also overcomes inhibition by MAG/myelin, and cAMP is elevated by neurotrophins. A PKA inhibitor present during priming abrogates the block of inhibition. Finally, if neurons are exposed to MAG/myelin and neurotrophins simultaneously, but with the Gi protein inhibitor, inhibition is blocked. We suggest that priming neurons with particular neurotrophins elevates cAMP and activates PKA, which blocks subsequent inhibition of regeneration and that priming is required because MAG/myelin activates a Gi protein, which blocks increases in cAMP. This is important for encouraging axons to regrow in vivo.  (+info)

Mechanisms for generating the autonomous cAMP-dependent protein kinase required for long-term facilitation in Aplysia. (7/7238)

The formation of a persistently active cAMP-dependent protein kinase (PKA) is critical for establishing long-term synaptic facilitation (LTF) in Aplysia. The injection of bovine catalytic (C) subunits into sensory neurons is sufficient to produce protein synthesis-dependent LTF. Early in the LTF induced by serotonin (5-HT), an autonomous PKA is generated through the ubiquitin-proteasome-mediated proteolysis of regulatory (R) subunits. The degradation of R occurs during an early time window and appears to be a key function of proteasomes in LTF. Lactacystin, a specific proteasome inhibitor, blocks the facilitation induced by 5-HT, and this block is rescued by injecting C subunits. R is degraded through an allosteric mechanism requiring an elevation of cAMP coincident with the induction of a ubiquitin carboxy-terminal hydrolase.  (+info)

Marker genes of decidualization: activation of the decidual prolactin gene. (8/7238)

Decidualization of human endometrial stromal (ES) cells in vitro is induced by cAMP analogues and ligands that elevate cellular cAMP levels in a manner resembling the gonadotrophins, prostaglandin E2 and relaxin (RLX). This differentiation process is marked by the onset of decidual prolactin (PRL) production in the late luteal phase of the cycle. Using transfection assays and a primary ES cell culture system, we have demonstrated that decidual PRL gene transcription is driven by an alternative upstream promoter (dPRL), approximately 6 kb upstream of the pituitary transcription start site. In primary cell cultures, RLX not only acutely but also permanently elevated cellular cAMP levels and induced PRL secretion after 6 days. Northern and Western blot analyses revealed all regulatory subunit isoforms (RIalpha, RIbeta, RIIalpha, RIIbeta) and catalytic subunits Calpha and Cbeta of protein kinase A (PKA) in ES cells. Transcript levels of PKA subunit isoforms are not altered during decidualization, but in decidualized ES cells exposed to elevated cellular cAMP levels by stimulation with RLX for >6 days, RIalpha protein levels were significantly reduced, whereas levels of all other forms remained unchanged. Reducing the availability of R subunits changed the R:C subunit ratio in favour of C and increased kinase activity. In transient transfections of undifferentiated ES cells, the dPRL promoter was activated by 8-Br-cAMP and by C subunit (Cbeta) of PKA. This induction, and the differentiation-dependent activity of the dPRL promoter in transfected decidualized cells, was effectively abolished by the co-expression of protein kinase inhibitor (PKI). A fragment of 332 bp of 5'-flanking region of the dPRL transcription start site was sufficient to mediate full inducibility by cAMP. cAMP activation of the dPRL promoter in ES cells was biphasic as an initial weak induction within 12 hours was followed by a subsequent, much more intense induction after 12 hours. The secondary induction was not seen with a control construct driven by a consensus cAMP response element (CRE) linked to a minimal promoter. The early response of the dPRL promoter depended upon a non-palindromic CRE at position -12 and mutation of this sequence led to omission of the early, but not of the delayed, induction. The major activation of the dPRL promoter depended upon a different region between position -332 and -270 since its deletion significantly reduced inducibility by cAMP. Its action was probably indirect as its kinetics differed from classic CRE-mediated responses, and it was specific to ES cells.  (+info)

*Neuronal memory allocation

Nguyen, P. V., & Woo, N. H. (2003). Regulation of hippocampal synaptic plasticity by cyclic AMP-dependent protein kinases. ... For example, the cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) pathways appear to participate in neuronal ... cyclic AMP responsive element-binding protein) in this process. Certain synapses on recruited neurons are more likely to ... The dendritic branch is the preferred integrative unit for protein synthesis-dependent LTP. Neuron 69, 132-146 (2011). Harvey, ...

*GP1BB

"Platelet glycoprotein Ib beta is phosphorylated on serine 166 by cyclic AMP-dependent protein kinase". J. Biol. Chem. 264 (26 ... GP1BB protein, human at the US National Library of Medicine Medical Subject Headings (MeSH) This article incorporates text from ... Du X, Harris SJ, Tetaz TJ, Ginsberg MH, Berndt MC (July 1994). "Association of a phospholipase A2 (14-3-3 protein) with the ... Du X, Harris SJ, Tetaz TJ, Ginsberg MH, Berndt MC (1994). "Association of a phospholipase A2 (14-3-3 protein) with the platelet ...

*BRSK2

"BRSK2 is activated by cyclic AMP-dependent protein kinase A through phosphorylation at Thr260". Biochemical and Biophysical ... BR serine/threonine-protein kinase 2 is an enzyme that in humans is encoded by the BRSK2 gene. GRCh38: Ensembl release 89: ... "LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1". The EMBO Journal. 23 (4): 833- ... "Entrez Gene: BRSK2 BR serine/threonine kinase 2". Human BRSK2 genome location and BRSK2 gene details page in the UCSC Genome ...

*HDAC8

"Negative regulation of histone deacetylase 8 activity by cyclic AMP-dependent protein kinase A". Mol. Cell. Biol. 24 (2): 765- ... The protein encoded by this gene belongs to class I of the histone deacetylase/acuc/apha family. It has histone deacetylase ... HDAC8 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH) This article incorporates text from ... Gantt SL, Gattis SG, Fierke CA (2006). "Catalytic activity and inhibition of human histone deacetylase 8 is dependent on the ...

*PRKACG

cAMP-dependent protein kinase catalytic subunit gamma is an enzyme that in humans is encoded by the PRKACG gene. Cyclic AMP- ... 1998). "Effects of [D-Ala1] peptide T-NH2 and HIV envelope glycoprotein gp120 on cyclic AMP dependent protein kinases in normal ... "Characterization of the cAMP-dependent protein kinase catalytic subunit Cgamma expressed and purified from sf9 cells". Protein ... "Entrez Gene: PRKACG protein kinase, cAMP-dependent, catalytic, gamma". Marx, S O; Reiken S; Hisamatsu Y; Jayaraman T; Burkhoff ...

*Tyrosine hydroxylase

"Direct phosphorylation of brain tyrosine hydroxylase by cyclic AMP-dependent protein kinase: mechanism of enzyme activation". ... that are phosphorylated by a variety of protein kinases. Ser40 is phosphorylated by the cAMP-dependent protein kinase. Ser19 ( ... is phosphorylated by the calcium-calmodulin-dependent protein kinase. MAPKAPK2 (mitogen-activated-protein kinase-activating ... "Molecular cloning of cDNA coding for brain-specific 14-3-3 protein, a protein kinase-dependent activator of tyrosine and ...

*Glycogen synthase

... two sites on glycogen synthetase phosphorylated by cyclic AMP-dependent protein kinase and their dephosphorylation by protein ... "A reinvestigation of the phosphorylation of rabbit skeletal-muscle glycogen synthase by cyclic-AMP-dependent protein kinase. ... protein kinase A (PKA), and casein kinase 2 (CK2). Each of these protein kinases lead to phosphorylated and catalytically ... Insulin stimulates glycogen synthase by inhibiting glycogen synthase kinases or/and activating protein phosphatase 1 (PP1) ...

*SOX9

Huang W, Zhou X, Lefebvre V, de Crombrugghe B (2000). "Phosphorylation of SOX9 by cyclic AMP-dependent protein kinase A ... SOX9 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH) SOX9 human gene location in the UCSC ... Transcription factor SOX-9 is a protein that in humans is encoded by the SOX9 gene. SOX-9 recognizes the sequence CCTTGAG along ... 1998). "Direct interaction of SRY-related protein SOX9 and steroidogenic factor 1 regulates transcription of the human anti- ...

*Dopamine receptor D1

This G-protein coupled receptor is Gs/a coupled and indirectly activates cyclic AMP-dependent protein kinase, stimulating the ... Dopamine receptor D1, also known as DRD1, is a protein that in humans is encoded by the DRD1 gene. Based upon Northern blot and ... "Regulation of transport of the dopamine D1 receptor by a new membrane-associated ER protein". Nat. Cell Biol. 3 (5): 492-8. doi ...

*PFKFB3

Expression of the promoter is shown to be induce by phorbol esters and cyclic-AMP-dependent protein kinase signaling. The four ... due to phosphorylation of Ser-460 by PKA or AMP-dependent protein kinase. The high '2-Kase' activity of PFKFB3 is also due to ... "Nuclear Targeting of 6-Phosphofructo-2-kinase (PFKFB3) Increases Proliferation via Cyclin-dependent Kinases". Journal of ... Manes NP, El-Maghrabi MR (June 2005). "The kinase activity of human brain 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase ...

*Stathmin

Identification of four sites phosphorylated in intact cells and in vitro by cyclic AMP-dependent protein kinase and p34cdc2". ... 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 ... "Serine 25 of oncoprotein 18 is a major cytosolic target for the mitogen-activated protein kinase". The Journal of Biological ...

*PRKX

... encodes a serine threonine protein kinase that has similarity to the catalytic subunit of cyclic AMP dependent protein kinases ... Huang S, Li Q, Alberts I, Li X (2016). "PRKX, a Novel cAMP-Dependent Protein Kinase Member, Plays an Important Role in ... Protein kinase, X-linked is a protein that in humans is encoded by the PRKX gene. This gene ... a phylogenetically and functionally distinct cAMP-dependent protein kinase, activates renal epithelial cell migration and ...

*RUNX1T1

"MTG8 proto-oncoprotein interacts with the regulatory subunit of type II cyclic AMP-dependent protein kinase in lymphocytes". ... Protein CBFA2T1 is a protein that in humans is encoded by the RUNX1T1 gene. The protein encoded by this gene is a putative zinc ... with serine/threonine protein kinases and heat shock protein HSP90 in human hematopoietic cell lines". Jpn. J. Cancer Res. 90 ( ... "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. doi:10.1038/ ...

*Merlin (protein)

"Cyclic AMP-dependent protein kinase phosphorylates merlin at serine 518 independently of p21-activated kinase and promotes ... protein kinase A, and p21 activated kinases. Work in Drosophila identified Merlin as an upstream regulator of the Hippo tumor ... Merlin is a member of the ERM family of proteins including ezrin, moesin, and radixin, which are in the protein 4.1 superfamily ... Merlin (also called Neurofibromin 2 or schwannomin) is a cytoskeletal protein. In humans, it is a tumor suppressor protein ...

*GSK-3

Separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase". Eur J Biochem. 107 (2): 519-27. doi:10.1111/j. ... Glycogen synthase kinase 3 is a serine/threonine protein kinase that mediates the addition of phosphate molecules onto serine ... "Structural insight into nucleotide recognition in tau-protein kinase I/glycogen synthase kinase 3 beta". Acta Crystallogr. D. ... The inactivation of GSK3B by various protein kinases also affects the adaptive immune response by inducing cytokine production ...

*PRKAR1A

Guild BC, Strominger JL (1984). "HLA-A2 antigen phosphorylation in vitro by cyclic AMP-dependent protein kinase. Sites of ... sequence formed by the fusion of ret tyrosine kinase and the regulatory subunit RI alpha of cyclic AMP-dependent protein kinase ... "A kinase anchoring protein (AKAP) interaction and dimerization of the RIalpha and RIbeta regulatory subunits of protein kinase ... cAMP-dependent protein kinase type I-alpha regulatory subunit is an enzyme that in humans is encoded by the PRKAR1A gene. cAMP ...

*CAMK2A

Phosphorylation by cyclic AMP-dependent protein kinase, protein kinase C, and calcium/calmodulin protein kinase; identification ... The product of this gene belongs to the Serine/Threonine protein kinases family, and to the Ca2+/calmodulin-dependent protein ... "Entrez Gene: CAMK2A calcium/calmodulin-dependent protein kinase (CaM kinase) II alpha". Walikonis RS, Oguni A, Khorosheva EM, ... cyclin-dependent kinase 5 activators p35 and p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II ...

*CACNB2

... of the sites phosphorylated by cyclic AMP-dependent protein kinase on the beta 2 subunit of L-type voltage-dependent calcium ... Voltage-dependent L-type calcium channel subunit beta-2 is a protein that in humans is encoded by the CACNB2 gene. Mutation in ... Bünemann M, Gerhardstein BL, Gao T, Hosey MM (1999). "Functional regulation of L-type calcium channels via protein kinase A- ... GeneReviews/NIH/NCBI/UW entry on Brugada syndrome CACNB2 protein, human at the US National Library of Medicine Medical Subject ...

*PRKAR2A

... type-II regulatory subunit of cyclic-AMP-dependent protein kinase by glycogen synthase kinase 3 and glycogen synthase kinase 5 ... "Ezrin is a cyclic AMP-dependent protein kinase anchoring protein". The EMBO Journal. 16 (1): 35-43. doi:10.1093/emboj/16.1.35. ... "A-kinase anchoring protein AKAP220 binds to glycogen synthase kinase-3beta (GSK-3beta ) and mediates protein kinase A-dependent ... Beebe SJ, Salomonsky P, Holroyd C, Becker D (Dec 1993). "Differential expression of cyclic AMP-dependent protein kinase ...

*Susan S. Taylor

... or cyclic AMP-dependent protein kinase. 1992: Elected to the American Academy of Arts and Sciences 1996: Elected to the ... She is known for her research on protein kinases, particularly protein kinase A. She was elected to the Institute of Medicine ... Taylor's research group has focused on the structure and function of protein kinases, particularly protein kinase A, since ... "Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase". Science. 253 (5018): ...

*ITPKA

It is also a substrate for the cyclic AMP-dependent protein kinase, calcium/calmodulin- dependent protein kinase II, and ... Lin AN, Barnes S, Wallace RW (1990). "Phosphorylation by protein kinase C inactivates an inositol 1,4,5-trisphosphate 3-kinase ... calmodulin-dependent protein kinase II phosphorylation mechanism". EMBO J. 16 (8): 1943-52. doi:10.1093/emboj/16.8.1943. PMC ... 2006). "Down-regulation of 1D-myo-inositol 1,4,5-trisphosphate 3-kinase A protein expression in oral squamous cell carcinoma". ...

*PREX1

Mayeenuddin LH, Garrison JC (Jan 2006). "Phosphorylation of P-Rex1 by the cyclic AMP-dependent protein kinase inhibits the ... 5-trisphosphate-dependent Rac exchanger 1 protein is a protein that in humans is encoded by the PREX1 gene. The protein encoded ... 2007). "Membrane translocation of P-Rex1 is mediated by G protein betagamma subunits and phosphoinositide 3-kinase". J. Biol. ... 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs ...

*Molecular and epigenetic mechanisms of alcoholism

Misra, K. and Pandey, S.C. (2006). The decreased cyclic-AMP dependent-protein kinase A function in the nucleus accumbens: a ... Some of the kinase families currently linked to alcoholism are Ca2+/calmodulin-dependent protein kinases (CaMKs), protein ... Ethanol enhances growth factor activation of mitogen-activated protein kinases by a protein kinase C-dependent mechanism. Proc ... Ethanol exposure alters the phosphorylation of cyclic AMP responsive element binding protein and cyclic AMP responsive element ...

*PRKACB

1998). "Effects of [D-Ala1] peptide T-NH2 and HIV envelope glycoprotein gp120 on cyclic AMP dependent protein kinases in normal ... Rabbi MF, al-Harthi L, Saifuddin M, Roebuck KA (1998). "The cAMP-dependent protein kinase A and protein kinase C-beta pathways ... "Evidence for two additional isoforms of the endogenous protein kinase inhibitor of cAMP-dependent protein kinase in mouse". J. ... 2003). "Mutants of protein kinase A that mimic the ATP-binding site of protein kinase B (AKT)". J. Mol. Biol. 329 (5): 1021-34 ...

*Scaffold protein

A-kinase anchor proteins (AKAPs), which target cyclic AMP-dependent protein kinase (PKA) to various sites in the cell. This ... Locasale, J.W., A.S. Shaw, and A.K. Chakraborty, Scaffold proteins confer diverse regulatory properties to protein kinase ... In three-kinase signaling cascades, scaffolds bind all three kinases, enhancing kinase specificity and restricting signal ... "Ste5 tethers multiple protein kinases in the MAP kinase cascade required for mating in S. cerevisiae". Cell. 78 (3): 499-512. ...

*Olfactory receptor neuron

The activated OR in turn activates the intracellular G-protein, GOLF (GNAL), adenylate cyclase and production of cyclic AMP ( ... "Phosphorylation and inhibition of olfactory adenylyl cyclase by CaM kinase II in Neurons: a mechanism for attenuation of ... "Molecular cloning and characterization of a calmodulin-dependent phosphodiesterase enriched in olfactory sensory neurons". Proc ... The surface of these cilia is covered with olfactory receptors, a type of G protein-coupled receptor. Each olfactory receptor ...
Cardiac myocyte ryanodine receptors (sarcoplasmic reticulum [SR] Ca release channel; cardiac ryanodine receptor [RyR2]) are localized in the junctional SR, in close proximity to L-type Ca channels (LTCCs) embedded in the membranes of the transverse (T)-tubules. This signaling microdomain has been termed the couplon,1 because it is here that excitation-contraction coupling takes place. As the heart fills with blood during diastole, RyR2 is stabilized in a closed state, allowing Ca uptake by the SR Ca ATPase to pump Ca from the cytoplasm into the SR, providing the primary source of Ca to activate the contractile apparatus during the next heart beat (systole). During systole, the cardiac action potential depolarizes the T-tubules and causes the opening of LTCCs. Ca influx through LTCCs elevates the [Ca] within the cytoplasmic space between the T-tubular and SR membrane, which promotes Ca binding to neighboring RyR2s, inducing some to open. Ca then moves out of the SR lumen into the subsarcolemmal, ...
Adenosine suppresses protein kinase A- and C-induced enhancement of glutamate release in the hippocampus.: Cultured hippocampal neurons from neonatal rats were
The data described above demonstrate a local PDE feedback regulation in cardiac myocytes whereby β1AR signals activate PDE4B3 via PKA-mediated phosphorylation. PKA-activated PDE4B, in turn, reduces the local steady-state cAMP concentration in a confined subsarcolemmal domain. The functional consequences of interrupting this feedback include increased PKA-mediated phosphorylation of Cav1.2 and RyR2, which is necessary for fine-tuning of ECC, a finding consistent with the cardiac phenotype of PDE4BKO mice (Leroy et al., 2011). Functional data on intracellular Ca2+ levels and contraction rate confirm the altered cAMP/PKA signaling in PDE4BKO myocytes. These conclusions are based on measurements of βAR-induced cAMP accumulation at the plasma membrane of PDE4BKO myocytes, the effects of acute PDE4B-selective inhibition in wild-type myocytes, the β1AR-dependent activation of PDE4B and the altered PKA-mediated phosphorylation of some, but not all substrates involved in Ca2+ homeostasis and ...
Voltage-gated sodium channels, which initiate action potentials in mammalian brain neurons, are modulated functionally by cAMP-dependent protein kinase A (PKA), resulting in reduced sodium current amplitude. Comparing brain and muscle sodium channels, we show that only the brain channel is modulated by PKA. The brain sodium channel I-II linker is both necessary and sufficient for PKA modulation, as shown by exchanging the I-II linker regions of the two channels. PKA consensus sites in the brain channel I-II linker were eliminated by deletion and site-specific mutagenesis. The mutant channels demonstrated decreased levels of phosphorylation when metabolically labeled in oocytes with [gamma-32P]-ATP, and they did not respond with a reduction in current magnitude after PKA induction. Modulation of the brain channel by PKA phosphorylation was mimicked by adding fixed negative charges at the PKA consensus sites, suggesting that the decrease in current was a direct result of the negative charge at one ...
We have previously shown that the protein kinase inhibitor β (PKIβ) form of the cAMP-dependent protein kinase inhibitor exists in multiple isoforms, some of which are specific inhibitors of the cAMP-dependent protein kinase, whereas others also inhibit the cGMP-dependent enzyme [Kumar, Van Patten and Walsh (1997), J. Biol. Chem. 272, 20011-20020]. We have now demonstrated that the switch from a cAMP-dependent protein kinase (PKA)-specific inhibitor to one with dual specificity arises as a consequence of alternate gene splicing. We have confirmed using bacterially produced pure protein that a single inhibitor species has dual specificity for both PKA and cGMP-dependent protein kinase (PKG), inhibiting each with very high and closely similar inhibitory potencies. The gene splicing converted a protein with 70 amino acids into one of 109 amino acids, and did not change the inhibitory potency to PKA, but changed it from a protein that had no detectable PKG inhibitory activity to one that now ...
cAMP-dependent protein kinase complex, cytoplasm, nucleus, cAMP-dependent protein kinase activity, mitochondrion organization, protein kinase A signaling, protein phosphorylation, Ras protein signal transduction
Mediates cAMP-dependent signaling triggered by receptor binding to GPCRs. PKA activation regulates diverse cellular processes such as cell proliferation, the cell cycle, differentiation and regulation of microtubule dynamics, chromatin condensation and decondensation, nuclear envelope disassembly and reassembly, as well as regulation of intracellular transport mechanisms and ion flux. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis ...
Protein kinases are able to recognize their appropriate targets in a complex milieu of cellular protein. This process must be carried out with high fidelity to ensure proper signal transduction in eukaryotic cells (Hunter 2000). In this study, we attempted to obtain insight into this recognition by examining PKA variants that exhibit a stable association with substrates. This binding provided a facile assay that allowed us to identify domains in both enzyme and substrates that were important for PKA phosphorylation. The substrate domains identified were physically removed from the sites of phosphorylation and were required for efficient recognition by PKA both in vivo and in vitro. To the best of our knowledge, these studies are the first to show that such distal sequence elements in substrates are required for phosphorylation by PKA. These observations may help explain why only a fraction of proteins that contain a PKA consensus site are phosphorylated by this enzyme in vivo (Budovskayaet al. ...
The first indication that PKA-mediated phosphorylation of the β2AR might do more than simply "desensitize" the receptor by inhibiting its coupling to Gs was provided by Okamoto et al. (1991). They demonstrated that a short peptide derived from the third cytoplasmic loop of the β2AR effectively activated purified Gs but only very weakly activated Gi in vitro. This peptide contains one of the two consensus PKA phosphorylation sites found in the receptor. When the peptide was phosphorylated by PKA, its ability to activate Gs was dramatically reduced, whereas its ability to activate Gi was reciprocally increased.. These results are essentially identical to findings in recent in vitro reconstitution studies with the intact recombinant human β2AR and recombinant Gsand Gi (Zamah et al., 2002). Reconstituted native β2AR mediates robust activation of Gs but not Gi. When the receptor is phosphorylated in vitro by PKA, Gscoupling is reduced, but Gi activation is markedly enhanced. The results are ...
The major objective of the present study was to further our understanding of the molecular mechanisms by which perturbations of the cAMP pathway regulate PKA subunit expression in neural cells. Indeed, the cAMP-induced down-regulation of PKA subunits described here contrasts with the findings reported for non-neural systems. In Sertoli cells, an extensively studied model system for PKA regulation (reviewed in Skålhegg and Taskén, 1997), activation of the cAMP pathway elevates PKA subunit protein levels along with a 2- to 4-fold increase in RIα, RIIα and Cα mRNA and a 50-fold increase in RIIβ mRNA. This up-regulation of mRNA levels involved both increased transcription and increased mRNA stability. In mouse epithelial cells (Lange-Carter and Malkinson, 1991), elevated levels of cAMP resulted in a similar increase in RIIβ mRNA but a decrease in mRNA for RIα and no change in that for RIIα. Earlier studies have suggested cAMP stimulated proteolytic degradation of C, but not R, subunits in ...
42 of the Chromas software package (Conor McCarthy, Southport, Australia). For all analyses, data obtained PLX3397 purchase with the forward and reverse primers were combined and aligned to the consensus sequence obtained from the BLAST GenBank database http://​www.​ncbi.​nlm.​nih.​gov/​nuccore/​166706780?​report=​genbank. Figure 1 Sequencing of the KRAS gene in DNA isolated from NSCLC tissues. (A) Wild type-(12Gly-GGT, 13Gly-GGC), (B) Mutant- (12Asp-GAT). Pyrosequencing In the pyrosequencing method for DNA sequence analysis [16, 17], inorganic phosphate released in the course of nucleotide incorporation serves as the initial substrate in a sequence of four. successive enzymatic reactions. This result in the emission of light, which functions as a signal that is proportional to the number of nucleotides incorporated. In this project, the PyroMark K-ras assay test (Biotage, Uppsala, Sweden) was used for primary amplification P005091 cost and pyrosequencing of both the 12th and ...
Second, the biological response to a second messenger can depend on the scaffolding complex that binds enzymes that synthesize or degrade the second messenger, and effectors (Figure 1B). There are numerous examples of this mode of operation in cells. A-kinase anchoring proteins (AKAPs) are known to localize cAMP-dependent protein kinase (PKA) to different subcellular compartments in the cell, thereby ensuring phosphorylation of PKA targets in the correct cellular vicinity.16 Some AKAPs have also been found to associate with cAMP-hydrolyzing PDE isoforms, thereby providing a mechanism for fine-tuning local cAMP levels and downstream effects of PKA.17 The PDE4D splice variant PDE4D3 binds to muscle-selective AKAP (mAKAP), and this association results in low cAMP levels and prevents PKA activation under basal conditions. Following stimulation of cAMP synthesis, however, PKA is activated and phosphorylates mAKAP. These phosphorylation events result in a more efficient PDE4D3 action, and provides a ...
In our work we develop and analyze an ordinary differential equation. model that describes the cyclic adenosine monophosphate (cAMP) --Protein Kinase A (PKA) pathway in budding yeast. In particular our. model describes the effect of glucose stimulation on the concentration of cAMP in the short term,. and the effect of stress in the long term. We develop this model in. order to understand two specific experimental results, reported by. Ma et al. (1999) and Garmendia-Torres et al. (2007). In order to describe the. surprising results published by Ma et al. (1999) we make a key assumption. that three enzymes within the cAMP-PKA network compete with one. another for activation by PKA. This assumption sets our model apart. from previous models of the cAMP-PKA network.. Our model focuses on two forms of negative feedback that. drive oscillations in the concentration of cAMP. Under high or low. stress conditions (for example, following glucose stimulation) our model reduces to a single ...
|P>PKA (Protein Kinase-A) is an enzyme that regulates processes as diverse as growth, development, memory, and metabolism. In its inactivated state, PKA exists as a tetrameric complex of two Catalytic subunits (PKA-C) and a Regulatory (PKA-R) subunit dimer. To date, [...]
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
1BKX: A binary complex of the catalytic subunit of cAMP-dependent protein kinase and adenosine further defines conformational flexibility.
In the hippocampus, the cAMP dependent protein kinase (PKA) plays critical roles in neurotransmission, cell excitability, and synaptic plasticity.All of these p...
cAMP-dependent protein kinase (PKA), ubiquitous in mammalian cells, regulates a plethora of cell processes including development, differentiation, memory, and m...
TY - JOUR. T1 - Protein kinase A-anchoring inhibitor peptides arrest mammalian sperm motility. AU - Vijayaraghavan, Srinivasan. AU - Goueli, Said A.. AU - Davey, Michael. AU - Carr, Daniel. PY - 1997/2/21. Y1 - 1997/2/21. N2 - Cyclic AMP-dependent protein kinase (PKA) is anchored at specific subcellular sites through the interaction of the regulatory subunit (R) with protein kinase A-anchoring proteins (AKAPs) via an amphipathic helix binding motif. Synthetic peptides containing this amphipathic helix domain competitively disrupt PKA binding to AKAPs and cause a loss of PKA modulation of cellular responses. In this report we use S-Ht31, a cell-permeant anchoring inhibitor peptide, to study the role of PKA anchoring in sperm. Our analysis of three species of mammalian sperm detected three isoforms of PKA (RIIα, RIIβ, and RIβ) and one 110-kDa AKAP. The addition of S-Ht31 to bovine caudal epididymal sperm inhibits motility in a time- and concentration-dependent manner. A control peptide, ...
Looking for online definition of cAMP-dependent protein kinase in the Medical Dictionary? cAMP-dependent protein kinase explanation free. What is cAMP-dependent protein kinase? Meaning of cAMP-dependent protein kinase medical term. What does cAMP-dependent protein kinase mean?
In the present study we demonstrated that IL-13, a Th2 cell-derived cytokine, is a potent arginase activator, and its induction of arginase contributes significantly to the suppression of NO production in LPS-activated macrophages. The increase in arginase activity is a result of de novo synthesis of arginase I mRNA and protein. Studies on the signaling molecules involved in arginase activation show that a surge in intracellular cAMP and the subsequent activation of PKA are obligatory for arginase induction. In addition, tyrosine kinases and p38 MAPK play a role in IL-13-induced arginase activation. To provide a perspective on our observations and conclusions, the results from the present study are discussed below in reference to previous findings regarding the signaling pathways involved in arginase activation and NO regulation by arginase.. In the present study despite the basal level of arginase I gene expression being detected in resting macrophages, arginase protein expression and enzyme ...
Lawler OA, Miggin SM, Kinsella BT (2001). "Protein kinase A-mediated phosphorylation of serine 357 of the mouse prostacyclin receptor regulates its coupling to G(s)-, to G(i)-, and to G(q)-coupled effector signaling.". J. Biol. Chem. 276 (36): 33596-607. PMID 11443126. doi:10.1074/jbc.M104434200. ...
TY - JOUR. T1 - Characterization of the bovine lens plasma membrane substrates for cAMP‐dependent protein kinase. AU - LOUIS, Charles F.. AU - JOHNSON, Ross. AU - JOHNSON, Keith. AU - TURNQUIST, Janet. PY - 1985/7. Y1 - 1985/7. N2 - cAMP‐dependent protein kinase, derived from either calf lens or bovine heart, promotes the phosphorylation of three lens plasma membrane proteins of molecular mass 28 kDa, 26 kDa and 18 kDa. Correlation of the maximal level of phosphorylation of these components with the Coomassie blue staining intensity of fractionated lens membranes suggests that the phosphorylation of the 28 kDa and 18 kDa components may be approximately stoichiometric. The protein kinase substrates could be dephosphorylated by a cardiac sarcoplasmic‐reticulum‐bound protein phosphatase activity. The 26 kDa component comigrated with MP26, the major lens membrane component that has been localized to the lens fiber cell junction. Treatment of phosphorylated lens membranes with chymotrypsin ...
The protein encoded by this gene is a regulatory subunit of cyclic AMP-dependent protein kinase A (PKA), which is involved in the signaling pathway of the second messenger cAMP. Two regulatory and two catalytic subunits form the PKA holoenzyme, disbands after cAMP binding. The holoenzyme is involved in many cellular events, including ion transport, metabolism, and transcription. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Aug 2015 ...
The occurrence of endogenous substrate proteins for Ca2+-dependent protein kinase, augmented by either phospholipid or calmodulin, and for cyclic AMP-dependent protein kinase was examined in homogenates and subcellular fractions of mouse pancreatic islets. Islet protein phosphorylation was enhanced by Ca2+-calmodulin; the major endogenous substrates in the homogenate were two proteins of Mr 53000 and 100000. The Mr-100000 phosphoprotein was localized to a 27000g-supernatant fraction, whereas the Mr-53000 phosphoprotein was present in a 27000g particulate fraction of mouse islets. In the presence of Ca2+, phosphatidylserine stimulated phosphorylation of 15 proteins, of Mr 17000-190000, in a 27000g-supernatant fraction. No effects of Ca2+ plus phosphatidylserine were observed in a 27000g particulate fraction of mouse islets. Examination of cyclic AMP-dependent protein phosphorylation revealed five substrate proteins, of Mr 23000-72000, present in the 27000g supernatant of mouse islets. No common ...
TY - JOUR. T1 - Cloning, characterization, and expression of the gene for the catalytic subunit of cAMP-dependent protein kinase in Caenorhabditis elegans. T2 - Identification of highly conserved and unique isoforms generated by alternative splicing. AU - Gross, Robert E.. AU - Bagchi, Srilata. AU - Lu, Xiangyi. AU - Rubin, Charles S.. PY - 1990. Y1 - 1990. N2 - The nematode Caenorhabditis elegans expresses substantial amounts of several forms (Mr values = 39,000-41,000) of the catalytic subunit (C) of cAMP-dependent protein kinase. Approximately 65% of the total cAMP-dependent phosphotransferase activity is recovered in particulate fractions of homogenates prepared from asynchronous populations of C. elegans. The C subunit is expressed at a low level in cytosolic and particulate compartments during embryogenesis. As the nematodes progress from late embryonic stages to the newly hatched, first larval (L1) stage, C subunit content increases 15-fold. High levels of C subunits are observed in ...
cAMP-dependent protein kinase inhibitor beta is a protein that in humans is encoded by the PKIB gene. The protein encoded by this gene is a member of the cAMP-dependent protein kinase inhibitor family. Studies of a similar protein in rat suggest that this protein may interact with the catalytic subunit of cAMP-dependent protein kinase and act as a competitive inhibitor. At least three alternatively spliced transcript variants encoding the same protein have been reported. GRCh38: Ensembl release 89: ENSG00000135549 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000019876 - Ensembl, May 2017 "Human PubMed Reference:". "Mouse PubMed Reference:". Zheng L, Yu L, Tu Q, Zhang M, He H, Chen W, Gao J, Yu J, Wu Q, Zhao S (Jan 2001). "Cloning and mapping of human PKIB and PKIG, and comparison of tissue expression patterns of three members of the protein kinase inhibitor family, including PKIA". Biochem J. 349 (Pt 2): 403-7. doi:10.1042/0264-6021:3490403. PMC 1221161 . PMID 10880337. "Entrez Gene: ...
Moen, Line Victoria; Ramberg, Håkon Andre; Zhao, Sen; Grytli, Helene Hartvedt; Sveen, Anita; Berge, Viktor; Skotheim, Rolf I.; Tasken, Kristin Austlid & Skålhegg, Bjørn Steen (2017). Observed correlation between the expression levels of catalytic subunit, C?2, of cyclic adenosine monophosphate-dependent protein kinase and prostate cancer aggressiveness. Urologic Oncology. ISSN 1078-1439. 35(3), s 111.e1- 111.e8 . doi: 10.1016/j.urolonc.2016.10.002 Vis sammendrag Background As an intracellular human pathogen, Mycobacterium tuberculosis (Mtb) is facing multiple stressful stimuli inside the macrophage and the granuloma. Understanding Mtb responses to stress is essential to identify new virulence factors and pathways that play a role in the survival of the tubercle bacillus. The main goal of this study was to map the regulatory networks of differentially expressed (DE) transcripts in Mtb upon various forms of genotoxic stress. We exposed Mtb cells to oxidative (H2O2 or paraquat), nitrosative ...
Cyclic AMP is a ubiquitous intracellular second messenger involved in the regulation of a wide variety of cellular processes, a majority of which act through the cAMP - protein kinase A (PKA) signalling pathway and involve PKA phosphorylation of specific substrates. PKA phosphorylation events are typically spatially restricted and temporally well controlled. A-kinase anchoring proteins (AKAPs) directly bind PKA and recruit it to specific subcellular loci targeting the kinase activity towards particular substrates, and thereby provide discrete spatiotemporal control of downstream phosphorylation events. AKAPs also scaffold other signalling molecules into multi-protein complexes that function as crossroads between different signalling pathways. Targeting AKAP coordinated protein complexes with high-affinity peptidomimetics or small molecules to tease apart distinct protein-protein interactions (PPIs) therefore offer important means to disrupt binding of specific components of the complex to better
Background The cAMP-dependent protein kinase (PKA) signaling transduction pathway has been shown to play an important role in the modulation of several ethanol (EtOH)-induced behavioral actions. In vivo, short-term exposure to EtOH up-regulates the cAMP-signaling cascade. Interestingly, different Ca2+-dependent cAMP-PKA cascade mediators play a critical role in the neurobehavioral response to EtOH, being of special relevance to the Ca2+-dependent adenylyl cyclases 1 and 8. We hypothesize an intracellular PKA activation elicited by EtOH administration, which may be regulated by a Ca2+-dependent mechanism as an early cellular response. Thus, the present work aims to explore the role of Ca2+ (internal and external) on the EtOH-activated PKA cascade. Methods Swiss male mice received an intraperitoneal injection of EtOH (0 or 4 g/kg), and brains were dissected following a temporal pattern (7, 15, 30, 45, 90, or 120 minutes). Either the enzymatic PKA activity or its fingerprint was analyzed on ...
Similarly to AA-dependent calcium entry, NO-activated calcium signals triggered by direct application of NO donors are significantly affected on pretreatment with PKI (Fig. 5B and C).. We do not know the identity of AA- and NO-activated channel(s) in B-TECs, although some candidates can be considered. TRPV1 and TRPV4 (both expressed in B-TEC) 5 are regulated by fatty acids, including AA, and their metabolites. They are also modulated by NO through S-nitrosylation and sensitized by PKA phosphorylation (37-40). TRPC3 and TRPC6 are activated by fatty acids and substrate for nitrosylation as well, and the cAMP/PKA pathway could enhance their insertion into the plasma membrane (34). Finally, in m3-HEK cell line, the so-called arachidonate-regulated channels require PKA phosphorylation and are composed of Orai1 and Orai3 proteins (35, 41).. B-TECs could express two (or more than two) types of calcium-permeable, PKA-dependent ion channels: one activated by AA and another by NO. Such hypothesis is in ...
ウサギ・ポリクローナル抗体 ab96186 交差種: Ms,Hu 適用: WB,ICC/IF…cAMP Protein Kinase Catalytic subunit抗体一覧…画像、プロトコール、文献などWeb上の情報が満載のアブカムの Antibody…
In this issue of Acta Physiologica, Benz et al. study the role of one important protein in the cyclic AMP signaling pathway, the A-kinase anchoring (AKAP)12. The downstream effects stemming from cAMP release are tightly controlled and activate a profusion of signaling pathways. However, many of these different processes function with largely the same major constituent proteins, including adenylate cyclases, kinases, phosphatases, and phosphodiesterases. cAMP-dependent protein kinase (PKA), which is the main intracellular target for cAMP, is widely found in these signaling assemblies, and is present at high concentrations in many tissues, playing varied roles in the regulation of molecular processes. Unexpectedly, despite its ubiquity there are only four isoforms of PKA regulatory subunit with which to impart functional and locational specificity ...
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
Doherty, P J.; Tsao, J; Schimmer, B P.; Mumby, M C.; and Beavo, J A., "Alteration of the regulatory subunit of type 1 camp-dependent protein kinase in mutant y1 adrenal cells resistant to 8-bromoadenosine 3:5-monophosphate." (1982). Subject Strain Bibliography 1982. 2372 ...
Both types of reciprocal antagonistic A2A-D2 receptor interactions coexist in the same cells. In fact, under normal conditions, there is a strong tonic activation of D2 receptors that blocks the ability of A2A receptors to signal through the cAMP-PKA pathway. Conversely, the antagonistic A2A-D2 receptor interaction determines the ability of A2A receptors to control the inhibitory role of D2 receptors in neuronal excitability and neurotransmitter release (Ferré et al., 2008).. In line with our previous studies (Calabresi et al., 1993; Picconi et al., 2004; Tozzi et al., 2007), we found that the application of D2 receptor agonists alone did not affect glutamate-mediated synaptic potentials/currents in striatal slices under physiological conditions. Conversely, simultaneous A2A receptor antagonism and D2 receptor activation resulted in a reduction of excitatory glutamatergic transmission. In our model, electrical stimulation of the slice mainly activates glutamatergic projections to the striatum. ...
Bacterial expression plasmid for GST tagged with a PKA phosphorylation site. Described in Ron D, Dressler H. "pGSTag: a versatile bacterial expression plasmid for enzymatic labeling of recombinant proteins". Biotechniques. 1992 Dec;13(6):866-9. Erratum in: Biotechniques 1993 Feb;14(2):221. Plasmid sequence in EMBL format is available for downloading here. ...
Complete information for AKAP5 gene (Protein Coding), A-Kinase Anchoring Protein 5, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
20E transmits signals through the ErGPCR-cAMP-PKA-CREB signaling pathway prior to the initiation of the gene expression through the EcR/UPS pathway
Camp Nursing, Camp nursing has its own unique twists: you are charged with the health care of many unknowns and this is where you can come to for answers. How do you... - pg. 7
TY - JOUR. T1 - Phosphoregulation of Cardiac Inotropy via Myosin Binding Protein-C during Increased Pacing Frequency or β1-Adrenergic Stimulation. AU - Tong, Carl W.. AU - Wu, Xin. AU - Liu, Yang. AU - Rosas, Paola C.. AU - Sadayappan, Sakthivel. AU - Hudmon, Andy. AU - Muthuchamy, Mariappan. AU - Powers, Patricia A.. AU - Valdivia, Héctor H.. AU - Moss, Richard L.. PY - 2015/5/4. Y1 - 2015/5/4. N2 - Background-Mammalian hearts exhibit positive inotropic responses to β-adrenergic stimulation as a consequence of protein kinase A-mediated phosphorylation or as a result of increased beat frequency (the Bowditch effect). Several membrane and myofibrillar proteins are phosphorylated under these conditions, but the relative contributions of these to increased contractility are not known. Phosphorylation of cardiac myosin-binding protein-C (cMyBP-C) by protein kinase A accelerates the kinetics of force development in permeabilized heart muscle, but its role in vivo is unknown. Such understanding is ...
cAMP-Protein Kinase A Activates Cystic Fibrosis Transmembrane Conductance Regulator for ATP Release from Rat Skeletal Muscle during Low pH or Contractions. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Purified proteoglycan subunits from human articular, bovine articular and nasal cartilages, and a rat chondrosarcoma were phosphorylated in vitro by beef heart cAMP-dependent protein kinase in the presence of gamma 32P-ATP. In these experiments, a maximum of 1.7 moles of 32P were incorporated per mole of proteoglycan from human cartilage. Phosphorylation was dependent on the presence of cAMP. Analysis by autoradiography revealed that serine residues in the core protein of the proteoglycan were the sites of phosphorylation. Treatment of proteoglycan subunits with chondroitinase ABC and alkaline phosphatase prior to reaction with cAMP-dependent protein kinase increased the incorporation of 32P by 12-30% when compared with untreated proteoglycans. These data indicate that proteoglycans in cartilage can be phosphorylated by cAMP-dependent protein kinase.
In vitro phosphorylation of the regulatory subunit of yeast cAMP-dependent protein kinase was studied. The cAMP-binding regulatory subunit (R subunit) can be multiply phosphorylated. Three distinct phosphorylation sites were inferred from the different ATP concentrations required for phosphorylation and from the presence of two discrete mobility shifts in NaDodSO4/polyacrylamide gel electrophoresis of the R subunit on phosphorylation. Limited tryptic digestion of the phosphorylated R subunit showed that a Mr 37,000 cAMP-binding peptide contained one of the phosphorylation sites and that a separate Mr 12,000 peptide contained another phosphorylation site. The yeast R subunit is therefore similar to the type II R subunit of mammalian origin, although it has a larger Mr (64,000 vs. 58,000) and is multiply phosphorylated. In vivo, both phosphorylated and unphosphorylated forms of the R subunit were found in cells grown in lactate or to stationary phase in 1.5% glucose, while cells grown in 5% ...
To characterize glucagon-like peptide (GLP)-1 signaling and its effect on renal endothelial dysfunction and glomerulopathy. We studied the expression and signaling of GLP-1 receptor (GLP-1R) on glomerular endothelial cells and the novel finding of protein kinase A-dependent phosphorylation of c-Raf at Ser259 and its inhibition of angiotensin II (Ang II) phospho-c-Raf(Ser338) and Erk1/2 phosphorylation. Mice overexpressing protein kinase C (PKC)β2 in endothelial cells (EC-PKCβ2Tg) were established. Ang II and GLP-1 actions in glomerular endothelial cells were analyzed with small interfering RNA of GLP-1R. PKCβ isoform activation induced by diabetes decreased GLP-1R expression and protective action on the renal endothelium by increasing its degradation via ubiquitination and enhancing phospho-c-Raf(Ser338) and Ang II activation of phospho-Erk1/2. EC-PKCβ2Tg mice exhibited decreased GLP-1R expression and increased phospho-c-Raf(Ser338), leading to enhanced effects of Ang II. Diabetic ...
Regulatory subunit of the cyclic AMP-dependent protein kinase (PKA), an effector of the Ras/cAMP pathway. Inhibits PKA activity in the absence of cAMP. cAMP activates PKA and promotes growth and proliferation in response to good nutrient conditions. Together with ZDS1, provides a negative feedback control on the cell wall integrity-signaling pathway by acting as a negative regulator of MAP kinase SLT2/MPK1.
cAMP is a second messenger that is essential for relaying hormonal responses in many biological processes. Spatial regulation of cAMP signaling is established by local degradation of cAMP by spatially restricted phosphodiesterases and, furthermore, by the confined targeting of the cAMP effector proteins. We have previously described several aspects of the spatiotemporal control of the cAMP effector Epac1. Epac1 is released from autoinhibition by the binding of cAMP (de Rooij et al., 1998; Rehmann, 2006, 2008), and in addition, diverse anchoring mechanisms, including plasma membrane targeting (Ponsioen et al., 2009; Gloerich et al., 2010), recruit Epac1 to specific subcellular localizations. This compartmentalization of Epac1 results in local activation of Rap, which couples Epac1 signaling to specific cellular processes. We now show that Epac1, in addition, is negatively regulated by its interaction with the nucleoporin RanBP2. We found that Epac1 directly interacts with the ZNFs of RanBP2, ...
Most PRKAR1A tumorigenic mutations lead to nonsense mRNA that is decayed; tumor formation has been associated with an increase in type II protein kinase A (PKA) subunits. The IVS6+1G>T PRKAR1A mutation leads to a protein lacking exon 6 sequences [R1 alpha Delta 184-236 (R1 alpha Delta 6)]. We compared in vitro R1 alpha Delta 6 with wild-type (wt) R1 alpha. We assessed PKA activity and subunit expression, phosphorylation of target molecules, and properties of wt-R1 alpha and mutant (mt) R1 alpha; we observed by confocal microscopy R1 alpha tagged with green fluorescent protein and its interactions with Cerulean-tagged catalytic subunit (C alpha). Introduction of the R1 alpha Delta 6 led to aberrant cellular morphology and higher PKA activity but no increase in type II PKA subunits. There was diffuse, cytoplasmic localization of R1 alpha protein in wt-R1 alpha- and R1 alpha Delta 6-transfected cells but the former also exhibited discrete aggregates of R1 alpha that bound C alpha; these were absent ...
Protein kinase A (PKA) is targeted to distinct subcellular localizations by specific protein kinase A anchoring proteins (AKAPs). AKAPs are divided into subclasses based on their ability to bind type I or type II PKA or both. Dual-specificity AKAPs were recently reported to have an additional PKA binding determinant called the RI specifier region. A bioinformatic search with the consensus RI specifier region identified a novel AKAP, the splicing factor arginine/serine-rich 17A (SFRS17A). Here, we show by a variety of protein interaction assays that SFRS17A binds both type I and type II PKA in vitro and inside cells, demonstrating that SFRS17A is a dual-specific AKAP. Moreover, immunofluorescence experiments show that SFRS17A colocalizes with the catalytic subunit of PKA as well as the splicing factor SC35 in splicing factor compartments. Using the E1A minigene splicing assay, we found that expression of wild type SFRS17A conferred regulation of E1A alternative splicing, whereas the mutant ...
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The acknowledged potential of small-molecule therapeutics targeting disease-related protein-protein interactions (PPIs) has promoted active research in this field. The strategy of using small molecule inhibitors (SMIs) to fight strong (tight-binding) PPIs tends to fall short due to the flat and wide interfaces of PPIs. Here we propose a biligand approach for disruption of strong PPIs. The potential of this approach was realized for disruption of the tight-binding (KD = 100 pM) tetrameric holoenzyme of cAMP-dependent protein kinase (PKA). Supported by X-ray analysis of cocrystals, bifunctional inhibitors (ARC-inhibitors) were constructed that simultaneously associated with both the ATP-pocket and the PPI interface area of the catalytic subunit of PKA (PKAc). Bifunctional inhibitor ARC-1411, possessing a KD value of 3 pM toward PKAc, induced the dissociation of the PKA holoenzyme with a low-nanomolar IC50, whereas the ATP-competitive inhibitor H89 bound to the PKA holoenzyme without disruption of the
As already mentioned, there are many other effects of cAMP. Lets have a look at another example. When there is an increase in cAMP levels, there is activation of transcription of various target genes in many animal cells. These target genes are known to contain the specific regulatory sequence called as the cAMP response element, generally abbreviated as CRE (diagramatic representation on the right side). Again, as described above, when cAMP binds to regulatory subunit of PKA, the catalytic subunit is released which carries the signal from cytoplasm to nucleus. Within the nucleus this activated PKA phosphorylates a transcription factor called CREB (CRE binding protein) at serine residue. This in turn recruits various co-activators and transcription of cAMP inducible genes takes place. This regulation of gene expression plays an important role in various processes like proliferation, differentiation, survival etc ...
|p|GF 109203X is a potent and selective inhibitor of protein kinase C [1].|/p||p| Protein kinase C (PKC) is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of serine and threon
TY - JOUR. T1 - Single nucleotide polymorphisms alter kinase anchoring and the subcellular targeting of A-kinase anchoring proteins. AU - Donelson Smith, F.. AU - Omar, Mitchell H.. AU - Nygren, Patrick J.. AU - Soughayer, Joseph. AU - Hoshi, Naoto. AU - Lau, Ho Tak. AU - Snyder, Calvin G.. AU - Branon, Tess C.. AU - Ghosh, Debapriya. AU - Langeberg, Lorene K.. AU - Ting, Alice Y.. AU - Santana, Luis Fernando. AU - Ong, Shao En. AU - Navedo, Manuel F. AU - Scott, John D.. PY - 2018/12/4. Y1 - 2018/12/4. N2 - A-kinase anchoring proteins (AKAPs) shape second-messenger signaling responses by constraining protein kinase A (PKA) at precise intracellular locations. A defining feature of AKAPs is a helical region that binds to regulatory subunits (RII) of PKA. Mining patient-derived databases has identified 42 nonsynonymous SNPs in the PKA-anchoring helices of five AKAPs. Solid-phase RII binding assays confirmed that 21 of these amino acid substitutions disrupt PKA anchoring. The most deleterious ...
within the GH-J clan. Moreover, besides the effect of substrate entrance on its own, we strongly suggest that a highly conserved arginine residue (in the RDP motif) rather than the previously proposed Tyr motif (not conserved) provides the proton to increase the pKa of the acid-base catalyst ...
Recombinant c-AMP dependant Protein Kinase A regulatory subunit 2 alpha from Prospec cat# pka-204. ProteoGenix provides you the best Kinases proteins.Shop now from our 200 000 + products.
Told me to go through GP and see if he would. It would probably make my oncologists head spin around. There have been a number of recent reports showing synergistic or enhanced effects on endpoints such as increased apoptosis and cell death in breast cancer cell lines when metformin is used in combination with chemotherapeutic drugs and with targeted therapies, providing a strong rationale for the use of metformin in clinical treatment regimens [ 78 - 80 ]. A downstream target for metformin was unknown until the discovery of the AMP protein kinase.. Do you take Herceptin and Metformin? Further, at the higher dose of metformin, serum insulin and leptin concentrations were reduced, but there were no effects observed on IGF-I, adiponectin or glucose levels.. It also curbs appetite a bit Tumor Ki67 labeling index, the primary endpoint, was significantly decreased from Prediabetes and hyperinsulinemia in breast cancer patients have also been associated with higher mortality rates [ 27 - 29 ].. One of ...
Adaptive Treg cells are induced in the tumor microenvironment. Vol. 14, Iss. 1, Role for the cAMP-Protein Kinase A Signaling Pathway in Suppression of Antitumor Immune Responses by Regulator... ...
Adaptive Treg cells are induced in the tumor microenvironment. Vol. 14, Iss. 1, Role for the cAMP-Protein Kinase A Signaling Pathway in Suppression of Antitumor Immune Responses by Regulator... ...
This gene encodes beta-2-adrenergic receptor which is a member of the G protein-coupled receptor superfamily. This receptor is directly associated with one of its ultimate effectors, the class C L-type calcium channel Ca(V)1.2. This receptor-channel complex also contains a G protein, an adenylyl cyclase, cAMP-dependent kinase, and the counterbalancing phosphatase, PP2A. The assembly of the signaling complex provides a mechanism that ensures specific and rapid signaling by this G protein-coupled receptor. This gene is intronless. Different polymorphic forms, point mutations, and/or downregulation of this gene are associated with nocturnal asthma, obesity and type 2 diabetes ...
cAMP-dependent protein kinase R2. (Aliases: BcDNA:GM01761,pkA,Cos,PKA RII,cos1,Pka-RII,Dmel\CG15862,CG15862,pka-RII,PKa-R2,PKA,Cos1,RII,RII[[DR]],PKA-R2,PKA-RII,Cos-1,Epa) ...
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Niles, R M. and Logue, M P., "Retinoid acid increases cyclic amp-dependent protein kinase activity in b16-f1 mouse melanoma cells. Abstr." (1979). Subject Strain Bibliography 1979. 1639 ...
cAMP signals are locally amplified by scaffold proteins (A Kinase Anchor Proteins, AKAPs) that tether cAMP-dependent Protein Kinase A (PKA) to discrete cellular locations. Here we hypothesized that mitochondrial anchoring of PKA promotes survival in muscle cells. We identified AKAP121 as the major mitochondrial AKAP in cardiomyocytes and aortic smooth muscle cells. In response to pressure overload, cardiac AKAP121 levels were significantly reduced, inducing marked mitochondrial dysfunction, DNA damage and activation of the DNA repair machinery. To test the role of AKAP121 in the modulation of cell survival, we synthesized peptides (AK-in) containing AKAP121 mitochondrial targeting domain but lacking its PKA binding motif, in order to competitively displace the endogenous AKAP121/PKA complex from mitochondria. Sequence-scrambled peptides were synthetized and used as controls (S). 24 hours after administration, FITC-conjugated AK-in peptides co-localized with mitochondria at confocal microscopy; ...
Objective. In human adipocytes the cAMP-dependent pathway mediates signals originating from beta-adrenergic activation, thus playing a key role in the regulation of important metabolic processes, i.e. lipolysis and thermogenesis. Cyclic AMP effects are mainly mediated by protein kinase A (PKA), whose R2B regulatory isoform is the most expressed in mouse adipose tissue, where it protects against diet-induced obesity and fatty-liver development. Aim of the study was to investigate possible differences in R2B expression, PKA activity and lipolysis in adipose tissues from obese and non-obese subjects. Research Design and Methods. The expression of the different PKA regulatory subunits were evaluated by immunohistochemistry, western blot and real-time PCR in subcutaneous and visceral adipose tissue samples from 20 non-obese and 67 obese patients. PKA activity and glycerol release were evaluated in total protein extract and adipocytes isolated from fresh tissue samples, respectively. Results. Expression
The subcellular distribution of protein kinase activity in isolated islets of Langerhans was determined. The majority (70%) of cyclic AMP-dependent protein kinase activity was located in the S-100 (soluble) fraction, while the majority (42%) of cyclic AMP-independent activity was located in the solublised P-100 (containing mitochondria, secretory granules and microsomes) fraction. Partial characterisation of the islet cyclic AMP-dependent protein kinase activity revealed the presence of two isozymes designated Type I and Type II. Type II kinase was the predominant isozyme of the S-100 fraction and Type I was the predominant isozyme found in the solublised P-100 fraction. Nonidet-P40 (a non-ionic detergent) was found to activate the S-100 cyclic AMP-dependent protein kinase activity, although no significant increase in protein kinase activity was observed when the P-0.6 (containing nuclei and cellular debris) fraction and P-100 fraction were solublised with Nonidet-P40. This activation was ...
We demonstrate that JunD, a component of the AP-1 transcription factor complex, activates transcription of the human proenkephalin gene in a fashion that is completely dependent upon the cAMP-dependent protein kinase, protein kinase A. Activation of proenkephalin transcription by JunD is dependent upon a previously characterized cAMP-, phorbol ester-, and Ca(2+)-inducible enhancer, and JunD is shown to bind the enhancer as a homodimer. Another component of the AP-1 transcription complex, JunB, is shown to inhibit activation mediated by JunD. As a homodimer JunB is unable to bind the enhancer; however in the presence of c-Fos, high-affinity binding is observed. Furthermore, JunD is shown to activate transcription of genes linked to both cAMP and phorbol ester response elements in a protein kinase A-dependent fashion, further blurring the distinction between these response elements. These results demonstrate that the transcriptional activity of an AP-1-related protein is regulated by the ...
Ver más] The small GTP-binding protein ADP-ribosylation factor 1 (ARF1) is an essential component of the molecular machinery that catalyzes the formation of membranebound transport intermediates. By using an in vitro assay that reproduces recruitment of cytosolic proteins onto purified, high salt-washed Golgi membranes, we have analyzed the role of cAMP-dependent protein kinase A (PKA) on ARF1 incorporation. Addition to this assay of either pure catalytic subunits of PKA (C-PKA) or cAMP increased ARF1 binding. By contrast, ARF1 association was inhibited following C-PKA inactivation with either PKA inhibitory peptide or RIIa as well as after cytosol depletion of C-PKA. C-PKA also stimulated recruitment and activation of a recombinant form of human ARF1 in the absence of additional cytosolic components. The binding step could be dissociated from the activation reaction and found to be independent of guanine nucleotides and saturable. This step was stimulated by C-PKA in an ATP-dependent manner. ...
CRC is the third leading cause of mortality in men and women worldwide [1]. Most of the cancer-related deaths in CRC patients are as a result of early spread of cancer cells or due to reoccurrence post-surgical interventions [15]. Alterations in some key regulatory molecules involved in cell cycle, apoptosis and EMT pathways have been proposed in the initiation of carcinogenesis [16]. In this context, efforts are being made to identify and characterize tumor associated molecules for development of therapeutic targets for cancer treatment. A unique class of tumor associated antigens called cancer testis (CT) antigens has been reported in various malignancies and have been shown to be associated with tumor growth and metastasis [4]. Only few CT antigens with abundant expression, namely sperm associated antigen (SPAG9) and AKAP4 have been shown to be associated with CRC [5, 10]. In this study, we examined the involvement of AKAP4 in various malignant properties at phenotype and molecular level of ...
VSMC and HUVEC proliferation and apoptosis were measured by BrdU and TdT staining, respectively. Balloon injury of the right carotid was produced in Wistar rats. Straight after the vascular injury, the balloon-dilated arteries were randomly transfected with p85active (n = 8), dominant negative p85 (p85DN) (n = 8) or green fluorescent protein (GFP, n = 6; controls). Transfection of p85active decreased VSMC proliferation in the absence of cAMP while cAMP inhibition of VSMC growth was prevented by p85DN. p85active formed a stable complex with ras proteins, resulting in a selective switch-off of ras effectors in VSMCs. On the other hand, p85active did not affect HUVEC growth in vitro. Interestingly, p85active significantly reduced VSMC and HUVEC apoptosis in vitro. In both vascular cell lineages, p85active increased while p85DN decreased Akt phosphorylation. Importantly, the in vivo transfection of activated p85-active significantly reduced VSMC proliferation and then neointimal formation after ...
The production of a mature vertebrate egg is a lengthy process in which the developing oocyte undergoes meiotic arrest followed by a long incubation period, before finally resuming meiosis in preparation for ovulation. The prevailing dogma in the field has been that, in Xenopus, meiotic arrest is released through a drop in cyclic adenosine monophosphate (cAMP) levels and protein kinase A (PKA) activity, which occurs following exposure to progesterone. In this issue (p. 1926), Khaled Machaca and colleagues provide evidence that challenges this dogma, as they demonstrate that no change is detectable in cAMP levels and PKA activity as meiotic arrest is released in the Xenopus oocyte. The authors use in vivo reporters to detect cAMP and PKA levels in real time in single cells, and show that there is no correlation between the rate of meiotic resumption and levels of cAMP or PKA inhibition. Furthermore, the authors develop conditions in which meiotic release is indeed possible in the presence of high ...
19. , and Brooker, G. (1977). Fluoride stimulation of slow Ca2+current in cardiac muscle. J . Mol. Cell. Cardiol. 9, 461-475. 20. , and Hofmann, F. (1982). Injection of subunits of cyclic AMP-dependent protein kinase into cardiac myocytes modulates Ca2+current. Nature (London) 298, 576-578. 21. , and Sperelakis, N. (1984). Injection of protein kinase inhibitor into cultured heart cells blocks calcium slow channels. A m . J. Physiol. 246, H630-H634. 22. , and Trautwein, W. (1986). On the mechanism of padrenergic regulation of the Ca2+channel in the guinea pig heart. 8Br-CAMP ( I mM) added to the bath produced a small stimulation of I,, (in the continued presence of G-kinase). This action of the cyclic nucleotide was also reversed by washout. The current tracings illustrated correspond to the two time points labeled a and b in the graph. 0 m M Ba2+as the charge camer. (H. Masuda and N. Sperelakis, 1994). lished, 1994). Note that inhibition of basal I,, began within about 90 sec after breaking into ...
Since the publication of Protein Kinases in 1994 many novel protein kinases have been discovered, but perhaps more importantly there have been dramatic advances in our understanding of the cellular functions of this remarkably diverse class of proteins. Protein Kinase Functions is not just an update of the previous edition but provides a new focus on the context and function of protein kinases, thus reflecting the recent advances in kinase biology.
butylphenol (2,6-DTBP), a nonanesthetic propofol derivative, reverses inflammation-mediated disinhibition through a specific interaction with heteromeric αβGlyRs containing phosphorylated α3 subunits. We expressed mutant GlyRs in HEK293T cells, and electrophysiological analyses of these receptors showed that 2,6-DTBP interacted with a conserved phenylalanine residue in the membrane-associated stretch between transmembrane regions 3 and 4 of the GlyR α3 subunit. In native murine spinal cord tissue, 2,6-DTBP modulated synaptic, presumably αβ heteromeric, GlyRs only after priming with PGE2. This observation is consistent with results obtained from molecular modeling of the α-β subunit interface and suggests that in α3βGlyRs, the binding site is accessible to 2,6-DTBP only after PKA-dependent phosphorylation. In murine models of inflammatory pain, 2,6-DTBP reduced inflammatory hyperalgesia in an α3GlyR-dependent manner. Together, our data thus establish that selective potentiation of GlyR ...
Publications, Scientific Experts, Research Topics, Species, Genomes and Genes, Research Grants about cyclic gmp dependent protein kinases
Intracellular cAMP levels are higher in LDLR-/−p110γ−/− than in LDLR−/−p110γ+/−macrophages.LDLR−/−p110γ+/− and LDLR−/−p110γ−/− BMM
ment, separation, and detection of the analytes were identifiedand optimized. The pH of the sample proved to be the mostinfluential variable during sample extraction. A critical impact onthe retention of the analytes on the cartridge material wasobserved, especially for sulfonamides caused by their aminogroups. Our enrichment tests between pH 2 and 6 revealed, asexpected, highest recoveries at pH 4 for the sulfonamides, whilethe recovery of the macrolides and trimethoprim showed nostrong pH dependence. This behavior can be explained by thecharge state of the sulfonamides at the particular pH values (Table1).26-31 With a compound specific pKa of 5-8 for the sulfonaminogroups (pKa 1) and a pKa of 2-2.5 for the arylamin (pKa 2), thesulfonamides are positively charged at pH 2 and negatively at a shows the breakdown curves for N4AcSMX and its four most pH above 5. The interaction with the cartridge material is strongest intense fragments as a function of the collision energy. As for analytes in ...
Forskolin is a ubiquitous activator of eukaryotic adenylyl cyclase (AC) in a wide variety of cell types, commonly used to raise levels of cAMP in the study and research of cell physiology.
Looking for online definition of cAMP-responsive element-binding protein 3-like protein 1 in the Medical Dictionary? cAMP-responsive element-binding protein 3-like protein 1 explanation free. What is cAMP-responsive element-binding protein 3-like protein 1? Meaning of cAMP-responsive element-binding protein 3-like protein 1 medical term. What does cAMP-responsive element-binding protein 3-like protein 1 mean?
TY - JOUR. T1 - Wound-healing effect of ginsenoside Rd from leaves of Panax ginseng via cyclic AMP-dependent protein kinase pathway. AU - Kim, Wang Kyun. AU - Song, Seung Yong. AU - Oh, Won Keun. AU - Kaewsuwan, Sireewan. AU - Tran, Tien Lam. AU - Kim, Won Serk. AU - Sung, Jong Hyuk. PY - 2013/2/28. Y1 - 2013/2/28. N2 - Panax ginseng is considered as one of the most valuable medicinal herbs in traditional medicine, and ginsenoside Rd is one of the main active ingredients in P. ginseng leaf. Although there is significant number of evidences implicated on the beneficial effects of the ginsenosides with diverse associated mechanisms, reports on the skin regeneration by the ginsenoside Rd are not sufficient. Therefore, we examined the mitogenic and protective effects of the ginsenoside Rd in the keratinocyte progenitor cells (KPCs) and human dermal fibroblasts (HDFs). Furthermore, the signaling pathways involved in the activation of KPCs and HDFs were investigated, and wound-healing effect is ...
en] Murine AIDS (MAIDS) is caused by infection with the murine leukemia retrovirus RadLV-Rs and is characterized by T-cell anergy and severe immunodeficiency with increased susceptibilty to several experimental opportunistic infections as observed in HIV infection. T cell anergy is associated with an increase of intracellular cAMP level, triggering a multistep pathway involving activation of PKA type I and resulting in inhibition of proximal TCR signaling. We have reviously demonstrated that blocking PKA type I using the selective inhibitor Rp-8-Br-cAMPS, restores T-cell function in vitro in MAIDS as well as in HIV infection. In the present report, we investigated the effect of parenteral administration of Rp-8-Br-cAMPS in mice with MAIDS. We show that the compound is not toxic and partially restores the ex vivo proliferative responses to anti-CD3 mAb, but that it has no effect on the lymphadenopathy and splenomegaly characterizing ...
Our data demonstrate the novel finding that GRK5 activity attenuates atherosclerosis, and that it does so through distinct antiatherogenic mechanisms in ECs, SMCs, monocytes, and Mϕs. These cell-specific mechanisms encompass diverse signaling systems, including the receptor tyrosine kinases CSF-1R and PDGFRβ, the 7-transmembrane receptor CCR2, the innate immunity receptors TLR4 and TNFR1, and the transcription factor NF-κB. Thus, despite data from overexpression and model cell systems suggesting the possibility that GRK5 could mediate proatherogenic activities,9,11,13,14 net physiological GRK5 activity clearly appears to be antiatherogenic.. Because GRK5-mediated phosphorylation of 7-transmembrane receptors promotes receptor/β-arrestin association,1 it may seem paradoxical that whereas GRK5 activity is antiatherogenic, β-arrestin2 activity is proatherogenic.19 However, at least 2 possibilities may help reconcile these findings. First, GRK5-mediated receptor phosphorylation may promote the ...
Thromboxane (TX) A2 and prostaglandin (PG) D2 mediate opposing actions in platelets and in vascular and non-vascular smooth muscle. Here, we investigated the effects of stimulation of the PGD2 receptor (DP) on signaling by the TXA2 receptor (TP) expressed in human platelets and in human embryonic kidney (HEK) 293 cells over-expressing the individual TPalpha and TPbeta isoforms. In platelets, the selective DP agonist BW245C abolished TP-mediated mobilization of intracellular calcium ([Ca2+]i) and inhibited platelet aggregation in response to the TXA2 mimetic U46619. DP-mediated desensitization of TP signaling in platelets was prevented by pre-treatment with the cAMP-dependent PKA inhibitor, H-89, but was unaffected by the PKC inhibitor GF 109203X. In HEK 293 cells signaling by TPalpha, but not TPbeta, was subject to DP mediated desensitization in a PKA dependent, PKC independent manner. U46619-induced signaling by TP-328, a truncated variant of TP containing only those residues common to TPalpha ...
Toxoplasma gondii encodes three protein kinase A catalytic (PKAc1‐3) and one regulatory (PKAr) subunits to integrate cAMP‐dependent signals. Here, we show that inactive PKAc1 is maintained at the parasite pellicle by interacting with acylated PKAr. Either a conditional knockdown of PKAr or the overexpression of PKAc1 blocks parasite division. Conversely, down‐regulation of PKAc1 or stabilisation of a dominant‐negative PKAr isoform that does not bind cAMP triggers premature parasite egress from infected cells followed by serial invasion attempts leading to host cell lysis. This untimely egress depends on host cell acidification. A phosphoproteome analysis suggested the interplay between cAMP and cGMP signalling as PKAc1 inactivation changes the phosphorylation profile of a putative cGMP‐phosphodiesterase. Concordantly, inhibition of the cGMP‐dependent protein kinase G (PKG) blocks egress induced by PKAc1 inactivation or environmental acidification, while a cGMP‐phosphodiesterase ...
The second messenger cyclic adenosine monophosphate (cAMP) plays a pivotal role in axonal growth and guidance, but its downstream mechanisms remain elusive. In this study, we report that type II protein kinase A (PKA) is highly enriched in growth cone filopodia, and this spatial localization enables the coupling of cAMP signaling to its specific effectors to regulate guidance responses. Disrupting the localization of PKA to filopodia impairs cAMP-mediated growth cone attraction and prevents the switching of repulsive responses to attraction by elevated cAMP. Our data further show that PKA targets protein phosphatase-1 (PP1) through the phosphorylation of a regulatory protein inhibitor-1 (I-1) to promote growth cone attraction. Finally, we find that I-1 and PP1 mediate growth cone repulsion induced by myelin-associated glycoprotein. These findings demonstrate that the spatial localization of type II PKA to growth cone filopodia plays an important role in the regulation of growth cone motility and ...
Skålhegg BS, Landmark B, Foss KB, Lohmann SM, Hansson V, Lea T and Jahnsen T. Institute of Pathology, Rikshospitalet, Oslo, Norway.. We have previously identified and characterized regulatory (R) subunits of cyclic AMP-dependent protein kinase, particularly the RII subunits in rat tissues (Jahnsen, T., Lohmann, S. M., Walter, U., Hedin, L., and Richards, J. S. (1985) J. Biol. Chem. 260, 15980-15987; Jahnsen, T., Hedin, L., Lohmann, S. M., Walter, U., and Richards, J. S. (1986) J. Biol. Chem. 261, 6637-6639; Jahnsen, T., Hedin, L., Kidd, V. J., Beattie, W. G., Lohmann, S. M., Walter, U., Durica, J., Schulz, T. Z., Schiltz, E., Browner, M., Lawrence, C. B., Goldman, D., Ratoosh, S. L., and Richards, J. S. (1986) J. Biol. Chem. 261, 12352-12361). These studies showed that rat RII alpha and RII beta had apparent molecular masses of 54 and 52 kDa, respectively. The aim of the present study was to purify and characterize cAMP-dependent protein kinase R subunits in human testis and to examine which of ...
PKA phosphorylation increases the tyrosine kinase activity of Csk towards an endogenous substrate. Tyrosine phosphorylation of heat-inactivated (65°C for 10 mi
Yotiao is an A-kinase anchoring protein (AKAP) that, in the heart, mediates the formation of a macromolecular complex consisting of the IKs channel (α subunit KCNQ1 and regulatory subunit KCNE1), protein kinase A (PKA), and protein phosphatase 1 (PP1). Mutations that disrupt this complex do not allow the channel to be regulated in response to stress and can cause death. The effects of PKA on the channel can be mimicked by mutation of Ser97 to Asp in the KCNQ1 subunit. Using cells transfected with this mutant form of the channel, Kurokawa et al. demonstrated that interaction with Yotiao increased channel current by slowing channel inactivation in the absence of adenosine 3′,5′-monophosphate (cAMP). This effect of Yotiao on the S97D channel was not blocked by inhibitors of PKA or protein kinase C (PKC), which indicates that Yotiao was not promoting phosphorylation of other sites on the channel. Disruption of the Yotiao interaction by mutation of the KCNQ1 leucine zipper domain blocked the ...
KLF15 knockdown also reduced the HBV DNA level in the serum (Fig. 7C). Similar to HBsAg profiles, this reduction effect was more prominent with 50 than with. 30 μg of KLF15 RNAi construct. To further confirm the effect of KLF15 on HBV replication, we generated an HBV genome with the CPm2 mutations that abolished the stimulatory effect of KLF15 on the core promoter (Fig. 2D). The replication efficiency of this HBV mutant plasmid in mice was then compared with that of the wild-type plasmid by hydrodynamic Alisertib molecular weight injection. As shown in Fig. 8, mice injected with the mutant genome had significantly lower levels of viral DNA in the sera than those injected with the wild-type genome (Mann-Whitney U = 27.0, P = 0.030, two-tailed). These results demonstrated the importance of the KLF15 response element in the core promoter in HBV replication. In this study, we demonstrated that the transcription factor, KLF15, could activate HBV major surface and core promoters (Figs. 1 and 2). The ...
It was assumed through most of the last century that cAMP signaling within mammalian cells proceeded mainly, if not exclusively, through activation of PKA (Kuo and Greengard, 1969). More recently, it has been appreciated that at least three major cAMP-dependent signaling pathways exist in rodent and human cells. A large number of molecular biological and pharmacological investigations have been devoted to parsing the relative contributions of PKA, Epac, and now NCS in cAMP-dependent signaling in mammalian, especially neuroendocrine, cells. These investigations have been fraught with the twin difficulties of establishing both (1) that a particular pathway is, in fact, cAMP-dependent and (2) that the pathway, if cAMP-dependent, relies on either canonical (PKA-dependent) or noncanonical (cAMP sensors other than PKA) signaling. Obviously, reagents for selective stimulation or inhibition of the various isoforms of adenylate cyclase have become increasingly central to these efforts. There is a ...
Our longest-running attempt to answer these questions involves a genetic study of a 60% identical Drosophila NF1 ortholog. Homozygous dNf1-null mutants are viable and normally patterned but reduced in size. Mutants also have electrophysiological, circadian rhythm and learning/memory defects. The size and cognitive deficits resemble human NF1 symptoms. Neither defect is readily modified by manipulating Ras signaling, but both are restored by increasing-or mimicked by decreasing-signaling through the cAMP/PKA pathway.. While others have reported that dNf1 has physically separable Ras and cAMP related functions, our work identified a neuronal Ras signaling defect as the proximal cause of dNf1 phenotypes. To shed further light on how excess neuronal Ras/ERK signaling causes various cAMP/PKA-sensitive phenotypes, we performed affinity capture mass spectroscopic identification of dNf1 protein complexes, determined gene expression profiles of dNf1 expressing brain and nonexpressing peripheral tissues, ...
The role of cAMP and its target, the cAMP-dependent protein kinase (also known as Protein Kinase A or PKA), in regulating myocardial function has been the subject of intense study for many decades. Recent technological developments in several areas including cell imaging, heterologous expression of proteins, transgenic and knockout animals has made it feasible to begin developing in silico models of this important signaling pathway that can be used to better understand the role of individaul components in the pathway, and the consequences of perturbing effects such as mutations and drugs. This lecture will review the current state of the art with regard to PKA signaling in cardiac myocytes and the many opportunities for mathematical biologists to aid in understanding important disease processes such as cardiac hypertrophy, heart failure, and cardiac arrhythmias ...
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TABLE-US-00006 TABLE 6 PKA-induced fluorescence change of peptide P1-P11 in the presence of the ten lead quencher dyes. Peptide concentration was fixed at 5 μM and a 5-, 10-, 25-, and 50-fold excess of quencher was employed. Fold excess Peptide Dye dye P1 P2 P3 P4 P5 P6 P7 P8 P9 P10 P11 D3 50 1.15 0.94 0.99 0.91 0.78 0.70 0.81 0.88 0.83 0.73 0.74 Evans 25 1.46 1.01 1.06 0.89 0.84 0.06 0.45 0.89 0.26 0.59 0.25 Blue 10 1.43 1.37 1.06 0.91 0.92 0.74 0.31 0.36 0.24 0.64 0.12 5 1.69 1.92 1.10 0.98 1.33 1.50 1.01 1.34 1.09 0.69 0.46 D6 50 3.85 6.30 1.68 4.27 5.79 4.70 5.20 5.01 4.03 3.48 2.46 Reactive 25 2.92 5.66 3.56 3.55 6.44 4.78 4.43 5.33 4.95 3.95 3.09 Blue 2 10 1.57 2.08 2.29 2.66 3.99 2.33 3.68 3.40 3.61 3.80 1.72 5 1.00 1.99 1.48 2.16 2.28 1.63 2.64 2.57 3.39 5.12 1.57 D18 50 1.10 3.71 0.31 0.59 1.12 1.52 0.48 0.45 0.65 0.72 0.30 Eriochrome 25 0.41 1.13 0.58 0.59 0.84 0.87 1.58 0.62 1.46 0.79 0.56 Black T 10 1.13 1.42 1.02 1.12 1.73 1.37 1.64 1.47 1.52 2.23 0.71 5 0.96 1.46 1.10 1.32 1.61 ...
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The beta 2 adrenergic receptor (beta 2AR) undergoes desensitization by a process involving its phosphorylation by both protein kinase A (PKA) and G protein-coupled receptor kinases (GRKs). The protein kinase A-anchoring protein AKAP79 influences beta 2AR phosphorylation by complexing PKA with the receptor at the membrane. Here we show that AKAP79 also regulates the ability of GRK2 to phosphorylate agonist-occupied receptors. In human embryonic kidney 293 cells, overexpression of AKAP79 enhances agonist-induced phosphorylation of both the beta 2AR and a mutant of the receptor that cannot be phosphorylated by PKA (beta 2AR/PKA-). Mutants of AKAP79 that do not bind PKA or target to the beta 2AR markedly inhibit phosphorylation of beta 2AR/PKA-. We show that PKA directly phosphorylates GRK2 on serine 685. This modification increases Gbeta gamma subunit binding to GRK2 and thus enhances the ability of the kinase to translocate to the membrane and phosphorylate the receptor. Abrogation of the ...
TY - JOUR. T1 - PKA-dependent regulation of the histone lysine demethylase complex PHF2-ARID5B. AU - Baba, Atsushi. AU - Ohtake, Fumiaki. AU - Okuno, Yosuke. AU - Yokota, Kenichi. AU - Okada, Maiko. AU - Imai, Yuuki. AU - Ni, Min. AU - Meyer, Clifford A.. AU - Igarashi, Katsuhide. AU - Kanno, Jun. AU - Brown, Myles. AU - Kato, Shigeaki. PY - 2011/6. Y1 - 2011/6. N2 - Reversible histone methylation and demethylation are highly regulated processes that are crucial for chromatin reorganization and regulation of gene transcription in response to extracellular conditions. However, the mechanisms that regulate histone-modifying enzymes are largely unknown. Here, we characterized a protein kinase A (PKA)-dependent histone lysine demethylase complex, PHF2-ARID5B. PHF2, a jmjC demethylase, is enzymatically inactive by itself, but becomes an active H3K9Me2 demethylase through PKA-mediated phosphorylation. We found that phosphorylated PHF2 then associates with ARID5B, a DNA-binding protein, and induce ...
TY - JOUR. T1 - Purification of a regulatory subunit of type II cAMP-dependent protein kinase from Drosophila heads. AU - Inoue, Hiroko. AU - Yoshioka, Tohru. PY - 1997/6/9. Y1 - 1997/6/9. N2 - The cytosolic extract from Drosophila heads was separated using anion-exchange column chromatography. Two types of cAMP-dependent protein kinase (PKA), type I and type II, were detected, and type II PKA was found to be a major isozyme. The regulatory subunit of type II PKA (RII) was purified, and only one isoform was observed. The purified protein had an apparent molecular mass of 51 kDa on SDS gel electrophoresis. Partial amino acid sequences of the protein were almost identical with the RIIα subunit of human. Since PKA has been implicated to be especially important for learning and memory in Drosophila, the RII subunit may play an essential role in the regulation of neuronal activity in the brain of Drosophila, and possibly in human.. AB - The cytosolic extract from Drosophila heads was separated using ...
TY - JOUR. T1 - Agonist dose-dependent phosphorylation by protein kinase A and G protein-coupled receptor kinase regulates β2 adrenoceptor coupling to Gi proteins in cardiomyocytes. AU - Liu, Ruijie. AU - Ramani, Biswarathan. AU - Soto, Dagoberto. AU - De Arcangelis, Vania. AU - Xiang, Yang Kevin. PY - 2009/11/20. Y1 - 2009/11/20. N2 - Adrenoceptors receptors (ARs) play a pivotal role in regulating cardiovascular response to catecholamines during β2ARs, prototypical G protein-coupled receptors (GPCRs), expressed in animal hearts, display dual coupling to both Gs and Gi proteins to control the adenylyl cyclase-cAMP dependent protein kinase A (PKA) pathway to regulate contraction responses. Here, we showed that β2AR coupling to Gi proteins was agonist dose-dependent and occurred only at high concentrations in mouse cardiac myocytes. Both β2AR-induced PKA activity, measured by fluorescence resonance energy transfer (FRET) imaging, and the increase in myocyte contraction rate displayed ...
A comparative analysis on protein kinases encoded in the completely sequenced genomes of two plant species, namely Arabidopsis thaliana and Oryza sativa spp japonica cv. Nipponbare is reported in the current study. We have analysed 836 and 1386 kinases identified from A. thaliana and the $O$. sativa genomes respectively. Their classification into known subfamilies reveals selective expansions of the plant receptor kinase subfamily comprising of Ser/Thr receptor kinases. The presence of calciumdependent kinases, and potential absence of cyclic nucleotide-dependent protein kinase of the type found in other (non-plant) eukaryotes, are other notable features of the two plant kinomes described here. An analysis on domain organisation of each of the protein kinases encoded in the plant genome has been carried out. Uncommon composition of functional domains like nuclear translocation factor domain, redox sensor domain (PAS), ACT and lectin domains are observed in few protein kinases shared between the ...

Purification of a regulatory subunit of type II cAMP-dependent protein kinase from Drosophila heads<...Purification of a regulatory subunit of type II cAMP-dependent protein kinase from Drosophila heads<...

Two types of cAMP-dependent protein kinase (PKA), type I and type II, were detected, and type II PKA was found to be a major ... Two types of cAMP-dependent protein kinase (PKA), type I and type II, were detected, and type II PKA was found to be a major ... Two types of cAMP-dependent protein kinase (PKA), type I and type II, were detected, and type II PKA was found to be a major ... Two types of cAMP-dependent protein kinase (PKA), type I and type II, were detected, and type II PKA was found to be a major ...
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Endogenous substrate for cyclic AMP-dependent protein kinase in adrenocortical polyadenylated messenger ribonucleoproteins |...Endogenous substrate for cyclic AMP-dependent protein kinase in adrenocortical polyadenylated messenger ribonucleoproteins |...

There is a possibility that this protein is a physiological substrate of cyclic AMP-dependent protein kinase and that the ... An endogenous polysomal cyclic AMP-dependent protein kinase specifically phosphorylates a 150,000-dalton peptide bound to an ... Endogenous substrate for cyclic AMP-dependent protein kinase in adrenocortical polyadenylated messenger ribonucleoproteins ... Endogenous substrate for cyclic AMP-dependent protein kinase in adrenocortical polyadenylated messenger ribonucleoproteins ...
more infohttp://science.sciencemag.org/content/210/4474/1137

Cyclic AMP-Dependent Protein Kinase Controls Virulence of the Fungal Pathogen Cryptococcus neoformans | Molecular and Cellular...Cyclic AMP-Dependent Protein Kinase Controls Virulence of the Fungal Pathogen Cryptococcus neoformans | Molecular and Cellular...

... of cyclic AMP and defective glucose repression in yeast strains with reduced activity of cyclic AMP-dependent protein kinase. ... Cyclic AMP-Dependent Protein Kinase Controls Virulence of the Fungal Pathogen Cryptococcus neoformans Cletus A. DSouza, J. ... 1999) Cyclic AMP-dependent protein kinase regulates pseudohyphal differentiation in Saccharomyces cerevisiae. Mol. Cell. Biol. ... ThePKA1 gene encoding the major cyclic AMP (cAMP)-dependent protein kinase catalytic subunit was identified and disrupted.pka1 ...
more infohttps://mcb.asm.org/content/21/9/3179?ijkey=649e5a071cddc72aaf2e336c5d3960baeb41c36f&keytype2=tf_ipsecsha

Endogenous substrate proteins for Ca2+-calmodulin-dependent, Ca2+-phospholipid-dependent and cyclic AMP-dependent protein...Endogenous substrate proteins for Ca2+-calmodulin-dependent, Ca2+-phospholipid-dependent and cyclic AMP-dependent protein...

Ca2+-phospholipid-dependent and cyclic AMP-dependent protein kinases in mouse pancreatic islets. P Thams, K Capito, C J ... Endogenous substrate proteins for Ca2+-calmodulin-dependent, Ca2+-phospholipid-dependent and cyclic AMP-dependent protein ... Endogenous substrate proteins for Ca2+-calmodulin-dependent, Ca2+-phospholipid-dependent and cyclic AMP-dependent protein ... Endogenous substrate proteins for Ca2+-calmodulin-dependent, Ca2+-phospholipid-dependent and cyclic AMP-dependent protein ...
more infohttp://www.biochemj.org/content/221/1/247

Cyclic AMP Dependent Protein Kinase A Regulatory Subunit 1a, Recombinant (cAMP PKA R1) | United States Biological | Biomol.comCyclic AMP Dependent Protein Kinase A Regulatory Subunit 1a, Recombinant (cAMP PKA R1) | United States Biological | Biomol.com

cAMP-dependent PKA is an ubiquitous serine/theonine protein kinase present in a variety of tissues (e.g. brain, skeletal muscle ... Cyclic AMP Dependent Protein Kinase A Regulatory Subunit 1a, Recombinant (cAMP PKA R1) ... Customer review for "Cyclic AMP Dependent Protein Kinase A Regulatory Subunit 1a, Recombinant (cAMP PKA R1)" ... Product information "Cyclic AMP Dependent Protein Kinase A Regulatory Subunit 1a, Recombinant (cAMP PKA R1)" ...
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Restricted efflux of the type II isoform of cyclic AMP-dependent protein kinase in permeabilized rat hepatocytes | Biochemical...Restricted efflux of the type II isoform of cyclic AMP-dependent protein kinase in permeabilized rat hepatocytes | Biochemical...

Restricted efflux of the type II isoform of cyclic AMP-dependent protein kinase in permeabilized rat hepatocytes. Olav K. ... Restricted efflux of the type II isoform of cyclic AMP-dependent protein kinase in permeabilized rat hepatocytes ... Restricted efflux of the type II isoform of cyclic AMP-dependent protein kinase in permeabilized rat hepatocytes ... Restricted efflux of the type II isoform of cyclic AMP-dependent protein kinase in permeabilized rat hepatocytes ...
more infohttp://www.biochemsoctrans.org/content/19/4/1161

Effect of indomethacin on the cyclic AMP-dependent protein kinase. | DocphinEffect of indomethacin on the cyclic AMP-dependent protein kinase. | Docphin

Effect of indomethacin on the cyclic AMP-dependent protein kinase. , European journal of pharmacology , 5/2/1980 ... Effect of indomethacin on the cyclic AMP-dependent protein kinase. R E Catalán M D Aragones A M Martinez M Armijo M Piña 5/2/ ... Catalán RE, Aragones MD, Martinez AM, Armijo M, Piña M. Effect of indomethacin on the cyclic AMP-dependent protein kinase. Eur ... Indomethacin inhibited cyclic AMP-dependent protein kinase activity in small intestine in in vivo experiments. An inverse ...
more infohttps://www.docphin.com/research/article-detail/15728797/PubMedID-6247165/Effect-of-indomethacin-on-the-cyclic-AMP-dependent-protein-kinase

Reversible phosphorylation of Drp1 by cyclic AMP‐dependent protein kinase and calcineurin regulates mitochondrial fission and...Reversible phosphorylation of Drp1 by cyclic AMPdependent protein kinase and calcineurin regulates mitochondrial fission and...

... dependent kinase and phosphatase, cyclic AMPdependent protein kinase (PKA) and calcineurin (also called protein phosphatase 2B ... Ser 656 is phosphorylated by cyclic AMPdependent protein kinase and dephosphorylated by calcineurin, and its phosphorylation ... Reversible phosphorylation of Drp1 by cyclic AMPdependent protein kinase and calcineurin regulates mitochondrial fission and ... Drp1, dynamin‐related protein 1; GFP, green fluorescent protein; PKA, cAMP‐dependent protein kinase, pS40 TH, phospho‐Ser 40 ...
more infohttp://embor.embopress.org/content/8/10/939?ijkey=5fc22c8fac9c53f38184d2f4c5d3fe3cdc0ede60&keytype2=tf_ipsecsha

Wound-healing effect of ginsenoside Rd from leaves of Panax ginseng via cyclic AMP-dependent protein kinase pathway<...Wound-healing effect of ginsenoside Rd from leaves of Panax ginseng via cyclic AMP-dependent protein kinase pathway<...

Wound-healing effect of ginsenoside Rd from leaves of Panax ginseng via cyclic AMP-dependent protein kinase pathway. In: ... Wound-healing effect of ginsenoside Rd from leaves of Panax ginseng via cyclic AMP-dependent protein kinase pathway. European ... Wound-healing effect of ginsenoside Rd from leaves of Panax ginseng via cyclic AMP-dependent protein kinase pathway. / Kim, ... title = "Wound-healing effect of ginsenoside Rd from leaves of Panax ginseng via cyclic AMP-dependent protein kinase pathway", ...
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Cyclic AMP-dependent protein kinase decreases gamma-aminobutyric acidA receptor-mediated 36Cl- uptake by brain microsacs. ...Cyclic AMP-dependent protein kinase decreases gamma-aminobutyric acidA receptor-mediated 36Cl- uptake by brain microsacs. ...

The effect of cyclic AMP (cAMP)-dependent protein phosphorylation on gamma-aminobutyric acidA (GABAA) receptor function was ... Cyclic AMP-dependent protein kinase decreases gamma-aminobutyric acidA receptor-mediated 36Cl- uptake by brain microsacs. ... Cyclic AMP-dependent protein kinase decreases gamma-aminobutyric acidA receptor-mediated 36Cl- uptake by brain microsacs.. ... The effect of cyclic AMP (cAMP)-dependent protein phosphorylation on gamma-aminobutyric acidA (GABAA) receptor function was ...
more infohttps://muscimol.xyz/1649259

Retinoid acid increases cyclic amp-dependent protein kinase activity i by R M. Niles and M P. Logue"Retinoid acid increases cyclic amp-dependent protein kinase activity i" by R M. Niles and M P. Logue

Retinoid acid increases cyclic amp-dependent protein kinase activity in b16-f1 mouse melanoma cells. Abstr. ... Niles, R M. and Logue, M P., "Retinoid acid increases cyclic amp-dependent protein kinase activity in b16-f1 mouse melanoma ...
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Roles of the AMP-activated and cyclic-AMP-dependent protein kinases in the adrenaline-induced inactivation of acetyl-CoA...Roles of the AMP-activated and cyclic-AMP-dependent protein kinases in the adrenaline-induced inactivation of acetyl-CoA...

Roles of the AMP-activated and cyclic-AMP-dependent protein kinases in the adrenaline-induced inactivation of acetyl-CoA ... phosphorylated by cyclic-AMP-dependent protein kinase) and Ser-79 (phosphorylated by the AMP-activated protein kinase). ... which is an antagonist of binding of cyclic AMP to the regulatory subunit of cyclic-AMP-dependent protein kinase, opposes the ... Roles of the AMP-activated and cyclic-AMP-dependent protein kinases in the adrenaline-induced inactivation of acetyl-CoA ...
more infohttps://scholars.duke.edu/display/pub691474

Isolation and characterization of a protein from rat testis which inhibits cyclic AMP-dependent protein kinase and...Isolation and characterization of a protein from rat testis which inhibits cyclic AMP-dependent protein kinase and...

Isolation and characterization of a protein from rat testis which inhibits cyclic AMP-dependent protein kinase and ... Isolation and characterization of a protein from rat testis which inhibits cyclic AMP-dependent protein kinase and ...
more infohttps://scholars.duke.edu/display/pub679460

Expression in Escherichia coli of BCY1, the regulatory subunit of cyclic AMP-dependent protein kinase from Saccharomyces...Expression in Escherichia coli of BCY1, the regulatory subunit of cyclic AMP-dependent protein kinase from Saccharomyces...

Expression in Escherichia coli of BCY1, the regulatory subunit of cyclic AMP-dependent protein kinase from Saccharomyces ... the regulatory subunit of cyclic AMP-dependent protein kinase from Saccharomyces cerevisiae. Journal of Biological Chemistry, ... The regulatory (R) subunit of cAMP-dependent protein kinase from the yeast Saccharomyces cerevisiae was expressed in ... protein types , enzymes , kinase. bioinformatics , genomics and proteomics , genetics & nucleic acid processing , protein ...
more infohttp://repository.cshl.edu/26201/

Reversible phosphorylation of Drp1 by cyclic AMP‐dependent protein kinase and calcineurin regulates mitochondrial fission and...Reversible phosphorylation of Drp1 by cyclic AMPdependent protein kinase and calcineurin regulates mitochondrial fission and...

... dependent kinase and phosphatase, cyclic AMPdependent protein kinase (PKA) and calcineurin (also called protein phosphatase 2B ... Ser 656 is phosphorylated by cyclic AMPdependent protein kinase and dephosphorylated by calcineurin, and its phosphorylation ... Reversible phosphorylation of Drp1 by cyclic AMPdependent protein kinase and calcineurin regulates mitochondrial fission and ... Drp1, dynamin‐related protein 1; GFP, green fluorescent protein; PKA, cAMP‐dependent protein kinase, pS40 TH, phospho‐Ser 40 ...
more infohttp://embor.embopress.org/content/8/10/939.export

The structure and expression of cyclic AMP-dependent protein kinase subunit genes in Caenorhabditis elegans and mouse Friend...The structure and expression of cyclic AMP-dependent protein kinase subunit genes in Caenorhabditis elegans and mouse Friend...

The structure and expression of cyclic AMP-dependent protein kinase subunit genes in Caenorhabditis elegans and mouse Friend ... cAMP-dependent protein kinase (PKA) regulates numerous cellular processes in eukaryotes in response to extracellular and ... Phosphorylation of substrate proteins leads to control of enzyme activity and/or gene expression. PKA is a heterotetramer ... Evidence is presented for the presence of this protein in the nematode. The C transcript is trans-spliced to the ubiquitous 22 ...
more infohttp://repository.yu.edu/handle/20.500.12202/3321

Somatic mutations of the catalytic subunit of cyclic AMP-dependent protein kinase (PRKACA) gene in Japanese patients with...Somatic mutations of the catalytic subunit of cyclic AMP-dependent protein kinase (PRKACA) gene in Japanese patients with...

Somatic mutations of the catalytic subunit of cyclic AMP-dependent protein kinase (PRKACA) gene in Japanese patients with ... Somatic mutations of the catalytic subunit of the cyclic AMP-dependent protein kinase (PRKACA) gene have recently been ...
more infohttps://phgkb.cdc.gov/PHGKB/phgHome.action?action=forward&dbsource=huge&id=112064

Cyclic AMPdependent protein kinase | definition of Cyclic AMPdependent protein kinase by Medical dictionaryCyclic AMPdependent protein kinase | definition of Cyclic AMPdependent protein kinase by Medical dictionary

Cyclic AMPdependent protein kinase explanation free. What is Cyclic AMPdependent protein kinase? Meaning of Cyclic AMPdependent ... protein kinase medical term. What does Cyclic AMPdependent protein kinase mean? ... Looking for online definition of Cyclic AMPdependent protein kinase in the Medical Dictionary? ... cAMP-dependent protein kinase. (redirected from Cyclic AMPdependent protein kinase) cAMP-dependent protein kinase. a tetrameric ...
more infohttp://medical-dictionary.thefreedictionary.com/Cyclic+AMPdependent+protein+kinase

Nathalie Rivard  - Free People Check with News, Pictures & Links  - Yasni.comNathalie Rivard - Free People Check with News, Pictures & Links - Yasni.com

Cyclic AMP-dependent protein kinase A negatively modulates adherens.... onlinelibrary.wiley.com ... The human homologue of the Drosophila Discs-large tumor suppressor protein, hDlg, is a multi-domain cytoplasmic protein that ... Activation of Cdk2 Stimulates Proteasome-dependent Truncation of.... www.jbc.org. Nathalie Rivard, Recipient of a Canadian ...
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Molecular mechanisms controlling the localisation of protein kinase A.  - PubMed - NCBIMolecular mechanisms controlling the localisation of protein kinase A. - PubMed - NCBI

Cyclic AMP-Dependent Protein Kinases/chemistry. *Cyclic AMP-Dependent Protein Kinases/genetics ... cAMP-dependent protein kinases (PKA) are ubiquitous signalling molecules that mediate many extracellular signals in eukaryotes ... Molecular mechanisms controlling the localisation of protein kinase A.. Griffioen G1, Thevelein JM. ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/12172960?dopt=Abstract

GPER | Cancer Genetics WebGPER | Cancer Genetics Web

Cyclic AMP-Dependent Protein Kinases. *Ovarian Cancer. *Tamoxifen. *Fatty Acids, Omega-3 ... which in turn activates protein kinase C, MAPK/ERK kinase, and ERK. The regulation of AVP by raloxifene and GPER may have ... We evaluated the role of GPER-1 in the mitogen-activated protein kinase (MAPK) signaling pathway using Western blot analysis. ... The G-protein-coupled estrogen receptor (GPR30, GPER-1) is a member of the G-protein-coupled receptor 1 family and is expressed ...
more infohttp://www.cancerindex.org/geneweb/GPER.htm

Taurine activates delayed rectifier Kv channels via a metabotropic pathway in retinal neurons.Taurine activates delayed rectifier Kv channels via a metabotropic pathway in retinal neurons.

EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases; EC 2.7.11.13/Protein Kinase C ... Cyclic AMP-Dependent Protein Kinases / physiology. Delayed Rectifier Potassium Channels / physiology*. HEK293 Cells. Humans. ... Protein Kinase C / physiology. Receptor, Serotonin, 5-HT2A / physiology*. Retinal Neurons / drug effects*, physiology. Taurine ... Moreover, we found that taurine enhanced K(V) channels via intracellular protein kinase C-mediated pathways. When 5-HT(2A) ...
more infohttp://www.biomedsearch.com/nih/Taurine-Activates-Delayed-Rectifier-KV/23045337.html

Two cAMP-dependent pathways differentially regulate exocytosis of large dense-core and small vesicles in mouse beta-cells.Two cAMP-dependent pathways differentially regulate exocytosis of large dense-core and small vesicles in mouse beta-cells.

... dependent exocytosis via protein kinase A (PKA) and exchange proteins directly activated by cAMP (Epac) in neurons and ... Cyclic AMP / physiology*. Cyclic AMP-Dependent Protein Kinases / metabolism. Cytoplasmic Vesicles / physiology. Exocytosis / ... 60-92-4/Cyclic AMP; 7440-70-2/Calcium; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases ... It has been reported that cAMP regulates Ca(2+)-dependent exocytosis via protein kinase A (PKA) and exchange proteins directly ...
more infohttp://www.biomedsearch.com/nih/Two-cAMP-dependent-pathways-differentially/17510178.html
  • C ) GST-Drp1 GED (aa 643-755) fusion proteins were phosphorylated in vitro with PKA and [γ‐ 32 P]ATP. (embopress.org)
  • Unfortunately, the biochemical precipitation techniques used to study the assembly of protein complexes are limited by steric hindrance from bulky fusion proteins or antibodies, use of detergents to solubilize complexes from cells, and poor yield of proteins precipitating through intermediate proteins. (rupress.org)
  • Pharmacological inhibition and genetic knockdown of exchange protein directly activated by cAMP 1 reduce pancreatic cancer metastasis in vivo. (semanticscholar.org)
  • In response to hormone- induced high cAMP levels, PKA phosphorylates glycogen synthetase (inhibition of the enzyme activity) and phosphorylase kinase to block glycogen synthesis. (biomol.com)
  • The inactivation is stable during purification in the presence of protein phosphatase inhibitors, and is associated with a 30-40% increase in the labelling of enzyme isolated from 32P-labelled cells. (duke.edu)
  • 4. As shown by okadaic acid inhibition, greater than 95% of the acetyl-CoA carboxylase phosphatase activity in extracts of rat adipocytes or liver is accounted for by protein phosphatase-2A, with less than 5% attributable to protein phosphatase-1. (duke.edu)
  • We also detected FRET between CaNA and PKA-RII bound simultaneously to AKAP79 within 50 Å of each other, thus providing the first direct evidence of a ternary kinase-scaffold-phosphatase complex in living cells. (rupress.org)
  • In a manner similar to the endocytosis motor dynamin, Drp1 is thought to polymerize into ring‐ or spiral‐shaped superstructures that constrict and eventually sever mitochondria by a GTP hydrolysis‐dependent mechanism ( Hoppins et al , 2007 ). (embopress.org)
  • Calcium-dependent exocytosis of SVs was potentiated by the cAMP-elevating agent forskolin, and the potentiating effect was unaffected by antagonists of PKA and was mimicked by the Epac-selective agonist 8-(4-chlorophenylthio)-2'-O-methyl cAMP, unlike that on LVs. (biomedsearch.com)
  • 60% of the molecules contained an N-terminal methionine, and 40% initiated with valine, the second amino acid of yeast R. The protein produced in E. coli migrated on a sodium dodecyl sulfate-polyacrylamide gel with an Mr of 52,000. (cshl.edu)
  • This table lists all participants of the complex (proteins, small molecules, nucleic acids, etc.) and their respective stoichiometry. (yeastgenome.org)
  • Dynamin‐related protein 1 (Drp1) is an ancient mechanoenzyme that uses GTP hydrolysis to power the constriction and division of mitochondria. (embopress.org)
  • Indomethacin, acetyl salicylic acid, eterylate and benorylate increased the protein kinase activity in liver, lung and heart after in vivo administration. (docphin.com)
  • Finally, we demonstrated AKAP79-regulated membrane localization of the MAGUK synapse-associated protein 97 (SAP97), suggesting that AKAP79 functions to organize even larger signaling complexes. (rupress.org)
  • In conclusion, this work demonstrates that the GTPase recognition of RRSP is independent of the nucleotide state and is mainly driven by the Ras and Rap1 switch I loop and also influenced by additional protein-protein interactions, increasing the substrate specificity of RRSP. (bireme.br)
  • In this study, we have directly visualized Ca(2+)-dependent exocytosis of both LVs and SVs with two-photon imaging in mouse pancreatic beta-cells. (biomedsearch.com)
  • N-terminal amino acid sequencing revealed that the expressed protein began with the natural sequence. (cshl.edu)
  • Results showed that protein banding patterns in both the cytoplasmic fraction and in a fraction enriched in chromatin-bound proteins showed some individual variability in tissues of different animals, but exhibited no changes that can be attributed to the flight. (nasa.gov)
  • Newly generated plasticity-related proteins (PRPs) can be captured by any tagged synapses, but untagged synapses are not eligible to receive new PPs. (wikipedia.org)
  • This protein therefore plays a role in the rapid nongenomic signaling events widely observed following stimulation of cells and tissues with estrogen. (cancerindex.org)
  • On the other hand, the actions of the cyclic AMP-sensitive and the Ca2+-phospholipid-sensitive systems may be overlapping, since two common substrates for them were noted in the 27000g-supernatant fraction. (biochemj.org)