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.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)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.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.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.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.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Cyclic GMP-Dependent Protein Kinases: A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.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 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.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.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.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.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.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.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.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.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.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.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.Kinetics: The rate dynamics in chemical or physical systems.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.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.Cyclic AMP-Dependent Protein Kinase Type I: A cyclic AMP-dependent protein kinase subtype primarily found in the CYTOPLASM. They are tetrameric proteins that contain two catalytic subunits and two type I-specific regulatory subunits.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)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.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.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.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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Sporothrix: A mitosporic Ophiostomataceae fungal genus, whose species Sporothrix schenckii is a well-known animal pathogen. The conidia of this soil fungus may be inhaled causing a primary lung infection, or may infect independently via skin punctures.Calmodulin-Binding Proteins: Proteins which bind calmodulin. They are found in many tissues and have a variety of functions including F-actin cross-linking properties, inhibition of cyclic nucleotide phosphodiesterase and calcium and magnesium ATPases.Phosphotransferases (Alcohol Group Acceptor): A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.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.Sulfonamides: A group of compounds that contain the structure SO2NH2.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.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.Trifluoperazine: A phenothiazine with actions similar to CHLORPROMAZINE. It is used as an antipsychotic and an antiemetic.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.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.Myosin-Light-Chain Kinase: An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.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.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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.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.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.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.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.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.Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.Death-Associated Protein Kinases: A family of calcium/calmodulin-dependent PROETIN-SERINE-THREONINE KINASES. They are ubiquitously expressed in adult and embryonic mammalian tissues, and their functions are tightly related to the early stages of eukaryotic programmed cell death.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.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.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.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.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.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.Mycelium: The body of a fungus which is made up of HYPHAE.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)Mitogen-Activated Protein Kinase Kinases: A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.Mitogen-Activated Protein 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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.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.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)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.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.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.Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.PhosphoproteinsNucleotides, CyclicEgtazic Acid: A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.Molecular Weight: The sum of the weight of all the atoms in a molecule.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.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.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.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.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.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Calcium, Dietary: Calcium compounds used as food supplements or in food to supply the body with calcium. Dietary calcium is needed during growth for bone development and for maintenance of skeletal integrity later in life to prevent osteoporosis.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.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.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.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.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.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.1-Phosphatidylinositol 4-Kinase: An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.

Modulation of Ca2+/calmodulin-dependent protein kinase II activity by acute and chronic morphine administration in rat hippocampus: differential regulation of alpha and beta isoforms. (1/1822)

Calcium/calmodulin-dependent protein kinase II (CaMK II) has been shown to be involved in the regulation of opioid receptor signaling. The present study showed that acute morphine treatment significantly increased both Ca2+/calmodulin-independent and Ca2+/calmodulin-dependent activities of CaMK II in the rat hippocampus, with little alteration in the protein level of either alpha or beta isoform of CaMK II. However, chronic morphine treatment, by which rats were observed to develop apparent tolerance to morphine, significantly down-regulated both Ca2+/calmodulin-independent and Ca2+/calmodulin-dependent activities of CaMK II and differentially regulated the expression of alpha and beta isoforms of CaMK II at protein and mRNA levels. Application of naloxone or discontinuation of morphine treatment after chronic morphine administration, which induced the withdrawal syndrome of morphine, resulted in the overshoot of CaMK II (at both protein and mRNA levels) and its kinase activity. The phenomena of overshoot were mainly observed in the beta isoform of CaMK II but not in the alpha isoform. The effects of both acute and chronic morphine treatments on CaMK II could be completely abolished by the concomitant application of naloxone, indicating that the effects of morphine were achieved through activation of opioid receptors. Our data demonstrated that both acute and chronic morphine treatments could effectively modulate the activity and the expression of CaMK II in the hippocampus.  (+info)

Muscarinic stimulation of calcium/calmodulin-dependent protein kinase II in isolated rat pancreatic acini. (2/1822)

AIM: To study whether M3 receptor occupation would lead to activation of calcium/calmodulin-dependent protein kinase II (CaM kinase II). METHODS: In this study, we isolated rat pancreatic acini by collagenase digestion; measured the Ca2+/calmodulin-independent activity of autophosphorylated form of the CaM kinase II both before and after stimulation of the acini with muscarinic secretagogue bethanechol (Bet). RESULTS: Bet stimulated the activation of, or generation of Ca(2+)-independent activity of, this kinase, in a concentration (0.0001-1 mmol.L-1) and time (5-300 s)-dependent manner; with Bet of 100 mumol.L-1, Ca(2+)-independent activity increased from an unstimulated level of 4.5 +/- 0.3 (n = 4) to 8.9 +/- 1.3 (n = 4, P < 0.05) at 5 s. Another Ca2+ mobilizing secretagogue cholecystokinin (CCK) also activated the kinase; at 1 mumol.L-1, CCK increased Ca(2+)-independent kinase activity to 12.9 +/- 0.5 (n = 6, P < 0.05). Vasoactive intestinal peptide (VIP) at 1 mumol.L-1 did not produce significant Ca(2+)-independent kinase activity (from control 3.90 +/- 0.28 to 4.53 +/- 0.47, n = 6, P > 0.05). Atropine completely blocked Bet activation of the kinase. CONCLUSION: CaM kinase II plays a pivotal role in digestive enzyme secretion, especially during the initial phase of amylase secretion.  (+info)

Calcium/calmodulin-dependent phosphorylation and activation of human Cdc25-C at the G2/M phase transition in HeLa cells. (3/1822)

The human tyrosine phosphatase (p54(cdc25-c)) is activated by phosphorylation at mitosis entry. The phosphorylated p54(cdc25-c) in turn activates the p34-cyclin B protein kinase and triggers mitosis. Although the active p34-cyclin B protein kinase can itself phosphorylate and activate p54(cdc25-c), we have investigated the possibility that other kinases may initially trigger the phosphorylation and activation of p54(cdc25-c). We have examined the effects of the calcium/calmodulin-dependent protein kinase (CaM kinase II) on p54(cdc25-c). Our in vitro experiments show that CaM kinase II can phosphorylate p54(cdc25-c) and increase its phosphatase activity by 2.5-3-fold. Treatment of a synchronous population of HeLa cells with KN-93 (a water-soluble inhibitor of CaM kinase II) or the microinjection of AC3-I (a specific peptide inhibitor of CaM kinase II) results in a cell cycle block in G2 phase. In the KN-93-arrested cells, p54(cdc25-c) is not phosphorylated, p34(cdc2) remains tyrosine phosphorylated, and there is no increase in histone H1 kinase activity. Our data suggest that a calcium-calmodulin-dependent step may be involved in the initial activation of p54(cdc25-c).  (+info)

Calcium/calmodulin-dependent protein kinase II is associated with the N-methyl-D-aspartate receptor. (4/1822)

The molecular basis of long-term potentiation (LTP), a long-lasting change in synaptic transmission, is of fundamental interest because of its implication in learning. Usually LTP depends on Ca2+ influx through postsynaptic N-methyl-D-aspartate (NMDA)-type glutamate receptors and subsequent activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). For a molecular understanding of LTP it is crucial to know how CaMKII is localized to its postsynaptic targets because protein kinases often are targeted to their substrates by adapter proteins. Here we show that CaMKII directly binds to the NMDA receptor subunits NR1 and NR2B. Moreover, activation of CaMKIIalpha by stimulation of NMDA receptors in forebrain slices increase this association. This interaction places CaMKII not only proximal to a major source of Ca2+ influx but also close to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptors, which become phosphorylated upon stimulation of NMDA receptors in these forebrain slices. Identification of the postsynaptic adapter for CaMKII fills a critical gap in the understanding of LTP because CaMKII-mediated phosphorylation of AMPA receptors is an important step during LTP.  (+info)

Ca2+/calmodulin-kinase II enhances channel conductance of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate type glutamate receptors. (5/1822)

The ability of central glutamatergic synapses to change their strength in response to the intensity of synaptic input, which occurs, for example, in long-term potentiation (LTP), is thought to provide a cellular basis for memory formation and learning. LTP in the CA1 field of the hippocampus requires activation of Ca2+/calmodulin-kinase II (CaM-KII), which phosphorylates Ser-831 in the GluR1 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate glutamate receptor (AMPA-R), and this activation/phosphorylation is thought to be a postsynaptic mechanism in LTP. In this study, we have identified a molecular mechanism by which CaM-KII potentiates AMPA-Rs. Coexpression in HEK-293 cells of activated CaM-KII with GluR1 did not affect the glutamate affinity of the receptor, the kinetics of desensitization and recovery, channel rectification, open probability, or gating. Single-channel recordings identified multiple conductance states for GluR1, and coexpression with CaM-KII or a mutation of Ser-831 to Asp increased the contribution of the higher conductance states. These results indicate that CaM-KII can mediate plasticity at glutamatergic synapses by increasing single-channel conductance of existing functional AMPA-Rs or by recruiting new high-conductance-state AMPA-Rs.  (+info)

Site-specific phosphorylation of synapsin I by Ca2+/calmodulin-dependent protein kinase II in pancreatic betaTC3 cells: synapsin I is not associated with insulin secretory granules. (6/1822)

Increasing evidence supports a physiological role of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) in the secretion of insulin from the pancreatic beta-cell, but the precise sites of action are not known. A role of this enzyme in neuroexocytosis is implicated by its phosphorylation of a vesicle-associated protein, synapsin I. Because of emerging similarities to the neuron with respect to exocytotic mechanisms, the expression and phosphorylation of synapsin I in the beta-cell have been studied. Synapsin I expression in clonal mouse beta-cells (betaTC3) and primary rat islet beta-cells was initially confirmed by immunoblot analysis. By immunoprecipitation, in situ phosphorylation of synapsin I was induced in permeabilized betaTC3 cells within a Ca2+ concentration range shown to activate endogenous CaM kinase II under identical conditions. Proteolytic digests of these immunoprecipitates revealed that calcium primarily induced the increased phosphorylation of sites identified as CaM kinase II-specific and distinct from protein kinase A-specific sites. Immunofluorescence and immunogold electron microscopy verified synapsin I expression in betaTC3 cells and pancreatic slices but demonstrated little if any colocalization of synapsin I with insulin-containing dense core granules. Thus, although this study establishes that synapsin I is a substrate for CaM kinase II in the pancreatic beta-cell, this event appears not to be important for the mobilization of insulin granules.  (+info)

Current studies on a working model of CaM kinase II in hippocampal long-term potentiation and memory. (7/1822)

There have been recent advances in understanding the molecular basis of the long-term potentiation (LTP) of synaptic transmission in the hippocampus. This review documents current views on mechanisms underlying LTP induction, from activation of the NMDA receptor to stimulation of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II). We will focus in particular on recent findings of how CaM kinase II encodes the frequency of synaptic usage and serves as a molecular memory switch at the synapse. Furthermore, a role for CaM kinase II in spatial learning and memory is demonstrated by recent studies using transgenic mice.  (+info)

Differential effects of a calcineurin inhibitor on glutamate-induced phosphorylation of Ca2+/calmodulin-dependent protein kinases in cultured rat hippocampal neurons. (8/1822)

Calcium/calmodulin-dependent protein kinases (CaM kinases) are major multifunctional enzymes that play important roles in calcium-mediated signal transduction. To characterize their regulatory mechanisms in neurons, we compared glutamate-induced phosphorylation of CaM kinase IV and CaM kinase II in cultured rat hippocampal neurons. We observed that dephosphorylation of these kinases followed different time courses, suggesting different regulatory mechanisms for each kinase. Okadaic acid, an inhibitor of protein phosphatase (PP) 1 and PP2A, increased the phosphorylation of both kinases. In contrast, cyclosporin A, an inhibitor of calcineurin, showed different effects: the phosphorylation and activity of CaM kinase IV were significantly increased with this inhibitor, but those of CaM kinase II were not significantly increased. Cyclosporin A treatment of neurons increased phosphorylation of Thr196 of CaM kinase IV, the activated form with CaM kinase kinase, which was recognized with an anti-phospho-Thr196 antibody. Moreover, recombinant CaM kinase IV was dephosphorylated and inactivated with calcineurin as well as with PP1, PP2A, and PP2C in vitro. These results suggest that CaM kinase IV, but not CaM kinase II, is directly regulated with calcineurin.  (+info)

TY - JOUR. T1 - Mutational analysis of Ca2+-independent autophosphorylation of calcium/calmodulin-dependent protein kinase II. AU - Mukherji, Sucheta. AU - Soderling, Thomas. PY - 1995/6/9. Y1 - 1995/6/9. N2 - Previous studies with synthetic peptides indicate that residues 290-309, corresponding to the calmodulin (CaM)-binding domain of Ca2+/CaM-dependent protein kinase II interact with the catalytic core of the enzyme as a pseudosubstrate (Colbran, R. J., Smith, M. K., Schworer, C. M., Fong, Y. L., and Soderling, T. R. (1989) J. Biol. Chem. 264, 4800-4804). In the present study, we attempted to locate the pseudosubstrate motif by generation or removal of potential substrate recognition sequences (RXXS/T) at selected positions using site-directed mutagenesis. Based on previous results, Arg297, Thr305/306, and Ser314 were selected as key residues. Single mutations such as N294S, K300S, A302R, A309R, and R311A were expressed, purified, and characterized. Several of the mutants exhibited decreased ...
TY - JOUR. T1 - Identification of a Ca2+/calmodulin-dependent protein kinase II regulatory phosphorylation site in non-N-methyl-D-aspartate glutamate receptors. AU - Yakel, Jerrel L.. AU - Vissavajjhala, Prabhakar. AU - Derkach, Victor A.. AU - Brickey, Debra A.. AU - Soderling, Thomas R.. PY - 1995/2/28. Y1 - 1995/2/28. N2 - Glutamate receptor ion channels are colocalized in postsynaptic densities with Ca2+/calmodulin-dependent protein kinase II (CaM-kinase II), which can phosphorylate and strongly enhance non-N-methyl-D-aspartate (NMDA) glutamate receptor current. In this study, CaM-kinase II enhanced kainate currents of expressed glutamate receptor 6 in 293 cells and of wild-type glutamate receptor 1, but not the Ser-627 to Ala mutant, in Xenopus oocytes. A synthetic peptide corresponding to residues 620-638 in GluR1 was phosphorylated in vitro by CaM-kinase II but not by cAMP-dependent protein kinase or protein kinase C. The 32P-labeled peptide map of this synthetic peptide appears to be the ...
TY - JOUR. T1 - Amphetamine activate protein kinase C and calcium/calmodulin-dependent protein kinase via NMDA receptor in primary cultures of rat cortical neurons. AU - Wu, Hsueh-Hsia. AU - Lee, Horng-Mo. PY - 1999. Y1 - 1999. M3 - Article. VL - 1. SP - 12. EP - 19. JO - New Taipei Journal of Medicine. JF - New Taipei Journal of Medicine. SN - 1562-4242. ER - ...
Authors Affiliations: 1Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Istituto di Endocrinologia e Oncologia Sperimentale del CNR Naples; 2Department of Neuroscience, Reproductive and Odontostomatological Sciences, University of Naples "Federico II", Naples; 3Department of Medicine-DIMED, Unit of Endocrinology, University of Padua, Padova; and 4Department of Medicine and Surgery, University of Salerno, Salerno, ...
We investigated the effects of Wenxin Keli (WXKL) on the Calcium/Calmodulin dependent kinase II (CaMK II) signal transduction pathway with transverse aortic constriction (TAC) rats. Echocardiographic measurements were obtained 3 and 9 weeks after the surgery. Meanwhile, the action potentials (APDs) were recorded using the whole-cell patch clamp technique, and western blotting was used to assess components of the CaMK II signal transduction pathway. At both 3 and 9 weeks after treatment, the fractional shortening (FS%) increased in the WXKL group compared with the TAC group. The APD|sub|90|/sub| of the TAC group was longer than that of the Sham group and was markedly shortened by WXKL treatment. Western blotting results showed that the protein expressions of CaMK II, phospholamban (PLB), and ryanodine receptor 2 (RYR2) were not statistically significant among the different groups at both treatment time points. However, WXKL treatment decreased the protein level and phosphorylation of CaMK II (Thr
Secretoneurin, a Novel Endogenous CaMKII Inhibitor, Augments Cardiomyocyte Calcium Handling and Inhibits Arrhythmogenic Calcium ...
Greiser and colleagues (10) also report that, consistent with previous studies, the remaining RyR2 clusters were hyperphosphorylated at the protein kinase A (PKA) phosphorylation site (Ser2808), which may compensate for the reduction in RyR2 protein expression and help sustain subsarcolemmal Ca2+ release despite reduced L-type Ca2+ currents (Figure 1B). However, RAP myocytes exhibited reduced RyR2 phosphorylation at the calmodulin-dependent protein kinase II (CaMKII) phosphorylation site (Ser2815) and no changes in CaMKII activity. This finding contrasts with previous studies that reported increased atrial CaMKII activity and CaMKII-dependent RyR2-Ser2815 phosphorylation in human AF (5). Moreover, other studies have shown that treatment with CaMKII inhibitors or selective disruption of the Ser2815 CaMKII phosphorylation site prevented AF in animal models through a reduction of SR Ca2+ leak (12). One explanation for this discrepancy could be the limited duration of pacing in the rabbit model used ...
TY - JOUR. T1 - Persistent reversal of enhanced amphetamine intake by transient CaMKII inhibition. AU - Loweth, Jessica A.. AU - Li, Dongdong. AU - Cortright, James J.. AU - Wilke, Georgia. AU - Jeyifous, Okunola. AU - Neve, Rachael L.. AU - Bayer, K. Ulrich. AU - Vezina, Paul. PY - 2013/1/23. Y1 - 2013/1/23. N2 - Amphetamine exposure transiently increases Ca2+/calmodulin-dependent protein kinase II (CaMKII) α expression in the nucleus accumbens (NAcc) shell and this persistently increases local GluA1 S831 phosphorylation and enhances behavioral responding to the drug. Here we assessed whether transiently interfering with CaMKII signaling using a dominant-negative CaMKIIα mutant delivered to the NAcc shell with herpes simplex viral vectors could reverse these long-lasting biochemical and behavioral effects observed following exposure to amphetamine. As expected, transient expression of CaMKIIα K42M in the NAcc shell produced a corresponding transient increase in CaMKIIα and decrease in ...
Nuclear factor-kappa beta (NF-kβ) pro-inflammatory signalling is important in modulating endothelial dysfunction and may be important in vascular dysfunction associated with the ageing process. Recent studies in the heart have highlighted Calcium/calmodulin-dependent protein kinase II (CaMKII) as a novel regulator of NF-kβ signalling. However nothing is known of the role this interaction could play in regulating dysfunction of the vasculature during ageing. Here we (i) characterise NF-kβ signalling in vascular endothelial cells and examine the potential for CaMKII modulation and (ii) determine whether CaMKIIδ expression is altered in ageing.. Using human umbilical vein endothelial cells (HUVECs) as an in vitro model system, initial experiments have established that pro-inflammatory NF-kB signalling is activated in response to both tumour necrosis factor α (TNF-α) and interleukin-1β (IL-1β) stimulation. This was shown by a significant reduction in IkBα expression (1.18 ± 0.16 vs. 0.48 ...
Three genes encoding different Ca2+/calmodulin-dependent protein kinases have been characterized in the wheat phytopathogenic fungus Stagonospora nodorum. The kinases were identified from the S. nodorum genome sequence on the basis of sequence homology to known Ca2+/calmodulin- dependent protein kinases. Expression analysis determined that each of the kinases was expressed during growth in vitro and also during infection. The onset of sporulation triggered increased transcript levels of each of the kinases, particularly CpkA where an 11-fold increase in expression was observed during sporulation in planta. The role of the kinases was further determined via a reverse genetics approach. The disruption of CpkA affected vegetative growth in vitro and also sporulation. The cpkA strains produced 20-fold less spores on complex media and were unable to sporulate on defined minimal media. Infection assays showed that CpkA was not required for lesion development but was essential for sporulation at the ...
Rationale:: In the failing heart, persistent β-adrenergic receptor (βAR) activation is thought to induce myocyte death by protein kinase A (PKA)-dependent and PKA-independent activation of calcium/calmodulin-dependent kinase II (CaMKII) β-Adrenergic signaling pathways are also capable of activating cardioprotective mechanisms. Objective: This study used a novel PKA inhibitor peptide (PKI) to inhibit PKA activity to test the hypothesis that βAR signaling causes cell death through PKA-dependent pathways and cardioprotection through PKA-independent pathways. Methods and Results: In PKI transgenic mice, chronic isoproterenol (ISO) failed to induce cardiac hypertrophy, fibrosis, myocyte apoptosis and depressed cardiac function. In cultured adult feline ventricular myocytes (AFVMs), PKA inhibition protected myocytes from death induced byβ1-AR agonists by preventing cytosolic and SR Ca2+ overload and CaMKII activation. PKA inhibition revealed a cardioprotective role of β-adrenergic signaling via ...
Studies over the past decade have demonstrated that SR Ca2+ release is abnormal in patients with chronic AF.2 Whereas the amplitude of the L-type Ca2+ current is generally decreased in AF, Ca2+ leak through RyR2 is typically elevated despite similar or decreased SR Ca2+ contents.2,5 It has been proposed that triggered activity due to DADs is caused by an inward depolarizing INCX current, which occurs in response to the removal of excess Ca2+ release from the cytosol.9,10 We provide direct experimental evidence for this mechanism in the FKBP12.6−/− mouse model of AF. Our data revealed that FKBP12.6−/− mice exhibit atrial focal activity and AF caused by SR Ca2+ leak, NCX activation, and DADs generation. Because recent studies revealed that CaMKII phosphorylation of RyR2 at S2814 is elevated in patients with chronic AF,4,5 we investigated whether inhibition of S2814 phosphorylation of RyR2 affected susceptibility of FKBP12.6−/− to AF. Our results demonstrate that inhibition of S2814 but ...
Author Summary Memory is understood as strengthened synaptic connections among neurons. Paradoxically components of synaptic membranes are relatively short-lived and frequently re-cycled while memories can last a lifetime. This suggests synaptic information is encoded at a deeper, finer-grained scale of molecular information within post-synaptic neurons. Long-term memory requires genetic expression, protein synthesis, and delivery of new synaptic components. How are these changes guided on the molecular level? The calcium-calmodulin dependent protein kinase II (CaMKII) has been heavily implicated in the strengthening of active neural connections. CaMKII interacts with various substrates including microtubules (MTs). MTs maintain cellular structure, and facilitate cellular cargo transport, effectively controlling neural architecture. Memory formation requires reorientation of this network. Could CaMKII-MT interactions be the molecular level encoding required to orchestrate neural plasticity? Using
CAMK2A - CAMK2A (Myc-DDK-tagged)-Human calcium/calmodulin-dependent protein kinase II alpha (CAMK2A), transcript variant 2 available for purchase from OriGene - Your Gene Company.
CaMKII alpha antibody (calcium/calmodulin-dependent protein kinase II alpha) for ICC/IF, IHC-Fr, WB. Anti-CaMKII alpha pAb (GTX127939) is tested in Mouse, Rat samples. 100% Ab-Assurance.
Objectives:Sepsis is associated with cardiac contractile dysfunction attributed to alterations in Ca2+ handling. We examined the subcellular mechanisms involved in sarcoplasmic reticulum Ca2+ loss that mediate altered Ca2+ handling and contractile dysfunction associated with sepsis.Design:Randomized
Mouse eggs are ovulated following arrest at metaphase of the second meiotic division (metII). Fertilization breaks this arrest, with the egg extruding a second polar body (PB2) and forming pronuclei. Ca2+ spikes induced by phospholipase C zeta, which are introduced into the egg on gamete fusion, are responsible for causing the degradation of Erp1/Emi2 (Fbxo43 - Mouse Genome Informatics) (Ducibella and Fissore, 2008; Jones, 2005; Mehlmann, 2005; Swann et al., 2006). Erp1/Emi2 loss activates the anaphase-promoting complex (APC) and so drives exit from meiosis (Madgwick et al., 2006; Shoji et al., 2006).. In frog eggs, the Ca2+ fertilization signal switches on calmodulin-dependent protein kinase II (CamKII; Camk2), which phosphorylates Erp1/Emi2 and so promotes its degradation (Liu and Maller, 2005; Rauh et al., 2005; Schmidt et al., 2005). Consistent with this more recent development in the understanding of the molecular events of activation, it had been discovered several years previously, also ...
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
Introduction: Glutamate excitotoxicity is an important mechanism of ischemic neuronal damage, however inhibition of glutamate receptors has proven an unsuccessful strategy. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a major downstream target of glutamate signaling. The aim of this study is to examine the neuroprotective potential of inhibition of autonomous CaMKII activity using novel peptide inhibitors (tatCN21,19o) and transgenic mice.. Methods: C57BL/6 male wild-type (WT) and T286A mutant mice were subjected to 6 min of cardiac arrest and CPR. Mice were randomized to tatCN21 (1 mg/kg), tatCN19o (0.01,0.1,1 mg/kg) or control (tatSCR; 1 mg/kg), administered 30 min after CPR (iv). Separate experiments were performed to assess mild post-arrest hypothermia (rectal T = 34 ±0.2 °C for 1 hr after CPR). Hippocampal neuronal damage was analyzed 3 days after CA/CPR by H&E staining. Total CaMKII and Thr-286 phosphorylation levels were measured by western blot. Statistical analyses were ...
CAMK2B - CAMK2B (Myc-DDK-tagged)-Human calcium/calmodulin-dependent protein kinase II beta (CAMK2B), transcript variant 7 available for purchase from OriGene - Your Gene Company.
Anti-peptide antibodies specific for the neuronal calcium channel alpha 1E subunit (anti-CNE1 and anti-CNE2) were produced to study the biochemical properties and subcellular distribution of the alpha 1E polypeptide from rat brain. Immunoblotting identified a single size form of 245-255 kDa which was a substrate for phosphorylation by cAMP- dependent protein kinase, protein kinase C, cGMP-dependent protein kinase, and calcium/calmodulin-dependent protein kinase II. Ligand- binding studies of alpha 1E indicate that it is not a high affinity receptor for the dihydropyridine isradipine or the peptide toxins omega- conotoxin GVIA or omega-conotoxin MVIIC at concentrations which elicit high affinity binding to other channel types in the same membrane preparation. The alpha 1E subunit is widely distributed in the brain with the most prominent immunocytochemical staining in deep midline structures such as caudate-putamen, thalamus, hypothalamus, amygdala, cerebellum, and a variety of nuclei in the ...
Since its inception, the "synaptic tagging hypothesis" has inspired many to search for synaptic tags. However, very few molecules have been proposed as candidates (Frey and Frey, 2008). The nature and identity of PRPs and synaptic tags are under intensive investigations (Frey and Frey, 2008). Two pathway experiments showed that blockade of protein kinase A (PKA) or its interaction with A kinase-anchoring proteins (AKAPs) prevents synaptic capture, suggesting that PKA or its anchoring at active synapses may serve as a synaptic tag for L-LTP (Huang et al., 2006; Young et al., 2006). Calcium/calmodulin-dependent protein kinase II (CaMKII) is also implicated as an L-LTP-specific tag (Sajikumar et al., 2007). Studies thus far have been based on the use of pharmacological inhibitors in two-pathway experiments. However, it is necessary to show that these tags are transiently and locally activated in a protein synthesis-independent manner by weak stimulation. In a recent study, NMDA-dependent, ...
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The Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a major mediator of long-term potentiation (LTP) and depression (LTD), two opposing forms of synaptic plasticity underlying learning, memory and cognition. The heterozygous CaMKIIα isoform KO (CaMKIIα+/-) mice have a schizophrenia-related phenotype, including impaired working memory. Here, we examined synaptic strength and plasticity in two brain areas implicated in working memory, hippocampus CA1 and medial prefrontal cortex (mPFC). Young CaMKIIα+/- mice (postnatal days 12-16; corresponding to a developmental stage well before schizophrenia manifestation in humans) showed impaired hippocampal CA1 LTP. However, this LTP impairment normalized over development and was no longer detected in older CaMKIIα+/- mice (postnatal weeks 9-11; corresponding to young adults). By contrast, the CaMKIIα+/- mice failed to show the developmental increase of basal synaptic transmission in the CA1 seen in wild-type (WT) mice, resulting in impaired basal
Complete information for CAMK4 gene (Protein Coding), Calcium/Calmodulin Dependent Protein Kinase IV, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
The concept of subcellular targeting by anchoring proteins is of major importance for understanding the specificity of signal transduction. The work presented here constitutes the first description of an anchoring protein for multifunctional CaM kinase II. αKAP exhibits three properties expected of anchoring proteins. (i) It is restricted to a specific cellular compartment, it is membrane bound and probably directly inserted into SR membranes by its N‐terminal hydrophobic domain (Figures 3 and 4). (ii) It binds CaM kinase II. This binding occurs within intact cells and not during extraction of transfected cells, since significant interaction was only detected after coexpression of αKAP and CaM kinase II, but not when individually expressed proteins were mixed (Figure 6). (iii) It is responsible for the targeting of the novel βM‐CaM kinase II to the SR, since it co‐immunoprecipitates with kinase extracted from SR membranes and the kinase does not have the physical properties of a ...
Lys-Lys-Lys-Leu-Arg-Arg-Gln-Glu-Ala-Phe-Asp-Ala-Tyr4374-v 0.5 mg | 90.00 EUR[Lys3, Phe10, Tyr13]-Autocamtide-2-Related Inhibitory Peptide ...
calmodulin-dependent protein kinase V: widely distributed in various tissues, involved in calcium-regulated processes; from rat brain; may exist in 40 & 41 kDa isoforms; amino acid sequence has been determined
The major finding of this study is that GIT1 is a novel mediator of Ang II-mediated VSMC gene transcription. Specifically we show that GIT1 participates in an Ang II signaling pathway that involves phosphorylation of HDAC5 and activation of MEF2, downstream of a pathway that requires Src, PLCγ, and CamK II (supplemental Figure V). Our results suggest that GIT1, via its multi-domain scaffolding function, coordinates Ang II signaling events that control calcium-dependent signaling (PLCγ and CamK II).. The focus of the present study is on CamK II which is a family of cytosolic serine/threonine protein kinases that exist as multimers consisting of α, β, δ, or γ subunits, each encoded by a different gene.24,25 Whereas CamK IIα and β are mainly expressed in neuronal tissues, CaMKIIδb, CaMKIIδc, and CaMKIIγ are abundant in the heart8,21,26 and VSMCs.27 CaMKII can phosphorylate type II HDACs.11 These HDACs (HDAC 4, 5, 7, and 9) normally repress transcriptional activity (eg, activation driven ...
Control of cardiomyocyte cytosolic Ca(2+) levels is crucial in determining inotropic status and ischemia/reperfusion stress response. Responsive to fluctuations in cellular Ca(2+), Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine kinase integral to the processes regulating cardiomyocyte Ca(2+) channels/transporters. CaMKII is primarily expressed either in the δB or δC splice variant forms, which may mediate differential influences on cardiomyocyte function and pathological response mechanisms. Increases in myocyte Ca(2+) levels promote the binding of a Ca(2+)/calmodulin complex to CaMKII, to activate the kinase. Activity is also maintained through a series of post-translational modifications within a critical region of the regulatory domain of the protein. Recent data indicate that the post-translational modification status of CaMKIIδB/δC variants may have an important influence on reperfusion outcomes. This study provided the first evidence that the specific type ...
SKF83959 is a high affinity dopamine D1 receptor agonist that has been reported to preferentially activate D1 receptors coupled to G(alpha)q. This pathway results in phosphatidylinositol hydrolysis, intracellular calcium mobilization, and potential activation of Ca2+/calmodulin-dependent protein kinase II alpha (CaMKIIalpha), an important regulator of synaptic transmission. Although the exact mechanism remains unclear, one recent model suggested that SKF83959 activates a D1/D2 receptor heteromer complex coupled to G(alpha)q. Here, we have used genetic models to define the signaling specificity of SKF83959 using behavioral endpoints. Furthermore, we have extended the behavioral characterization of SKF83959 on motor output and additionally defined SKF83959-induced effects on anxiety and depressive-like behaviors. In wildtype mice, a peripheral injection of SKF83959 (1mg/kg) produced a modest but significant increase in horizontal locomotor activity and orofacial grooming. The SKF83959-induced ...
Camk2d2 antibody (calcium/calmodulin-dependent protein kinase (CaM kinase) II delta 2) for IHC-P, WB. Anti-Camk2d2 pAb (GTX124377) is tested in Zebrafish samples. 100% Ab-Assurance.
Previous work has shown that neurotrophins rapidly potentiate synaptic transmission through presynaptic mechanisms. The acute potentiation of transmitter release by BDNF is accompanied by a rise in [Ca2+]i in both the NMJ (Stoop and Poo 1995) and at the CNS synapses (Berninger and Garcia 1993; Marsh and Palfrey 1996; Sakai et al. 1997; Li et al. 1998). However, it is unclear whether and how the increase in [Ca2+]i mediates the neurotrophin-induced synaptic potentiation and which downstream signaling events are involved. In this paper we report a surprising finding that the acute potentiation of transmitter release by NT3 at the neuromuscular synapses is independent of Ca2+ influx from extracellular sources. Instead, this potentiation is mediated by Ca2+ released from intracellular stores through IP3 and ryanodine receptors. Thus, the mechanisms by which BDNF and NT3 modulate transmitter release could be quite different. Furthermore, we demonstrated that Ca2+ released from intracellular stores is ...
Calcium and calmodulin-dependent protein kinase II (CaMKII) plays a fundamental role in the synaptic plasticity events that underlie learning and memory. Regulation of CaMKII kinase activity occurs through an autoinhibitory mechanism in which a regulatory domain of the kinase occupies the catalytic site and calcium/calmodulin activates the kinase by binding to and displacing this regulatory domain. A single putative ortholog of CaMKII, encoded by unc-43, is present in the Caenorhabditis elegans nervous system. Here we examined UNC-43 subcellular localization in the neurons of intact animals and show that UNC-43 is localized to clusters in ventral cord neurites, as well as to an unlocalized pool within these neurites. A mutation that mimics autophosphorylation within the regulatory domain results in an increase in the levels of UNC-43 in the unlocalized neurite pool. Multiple residues of CaMKII facilitate the interaction between the catalytic domain and the regulatory domain, thereby keeping the ...
Previous studies indicate that LTP induction increases the CaMKII-dependent phosphorylation of GluR1 at Ser831. Although such phosphorylaton may enhance the function of synaptic receptors, this phosphorylation does not seem to be required for receptor delivery: tCaMKII can deliver GluR1(S831A)-GFP to the synapse. Our results indicate that some protein(s) other than GluR1 must be substrate(s) of CaMKII (Choquet: Stargazin) and participate in the regulated synaptic delivery of AMPARs ...
FUNCTION: ACTIVATES TYROSINE AND TRYPTOPHAN HYDROXYLASES IN THE PRESENCE OF CA(2+)/CALMODULIN-DEPENDENT PROTEIN KINASE II, AND STRONGLY ACTIVATES PROTEIN KINASE C. IS PROBABLY A MULTIFUNCTIONAL REGULATOR OF THE CELL SIGNALING PROCESSES MEDIATED BY BOTH KINASES ...
Association of NCAM140 with lipid rafts is required for CaMKIIα activation. (A, left) Representative images of neurites of cultured hippocampal neurons treated
Usled njihove sposobnosti da se autofosforilišu, CaMK aktivnost može da bude dugotrajnija od intracelularnog kalcijuma koji je neophodan za njihovu aktivaciju. U neuronima, ova osobina je važna za indukciju sinaptičke plastičnosti.[2] Farmakološka inhibicija CaMKII blokira indukciju dugotrajne potencijacije. Nakon aktivacije, CaMKII fosforiliše postsinaptičke glutamatne receptore i time menja električne osobine sinapse.. ...
Looking for online definition of CaM kinase II delta subunit in the Medical Dictionary? CaM kinase II delta subunit explanation free. What is CaM kinase II delta subunit? Meaning of CaM kinase II delta subunit medical term. What does CaM kinase II delta subunit mean?
Excessive activation of β-adrenergic, angiotensin II, and aldosterone signaling pathways promotes mortality after myocardial infarction (MI), while antagonist drugs targeting these pathways are core therapies for treating post-MI patients. The multifunctional calcium/calmodulin-dependent protein kinase II (CaMKII) is activated by catecholamines and angiotensin II, and CaMKII inhibition prevents isoproterenol- and angiotensin II-mediated cardiomyopathy. Here we ask the hypothesis if aldosterone and CaMKII participated in common responses to MI by developing a mouse MI model supplemented by aldosterone infusion (MI+Aldo) to approximate plasma aldosterone levels measured in MI patients. We find that aldosterone exerts direct toxic actions on myocardium by oxidative activation of CaMKII, causing cardiac rupture and increased mortality in mice after MI (65.5% for aldosterone versus 31.0% for vehicle, P=0.007, n≥19 mice per treatment). Aldosterone oxidizes CaMKII by recruiting NADPH oxidase, and ...
Our data show that LTP inducing stimulation produces a 6-fold increase in endogenous synapsin I phosphorylation at its CaM kinase II sites. The observed rise in synapsin I phosphorylation occurred rapidly after the stimulation and persisted for at least 30 min. Most importantly, this effect was not observed in the presence of the NMDA receptor antagonist APV, suggesting that the rise in synapsin I phosphorylation is due to the LTP-inducing nature of the stimulation. Since synapsin I is localized exclusively in the presynaptic terminal, our data provide strong evidence that LTP expression is accompanied by persistent biochemical changes in the presynaptic terminal. Because the observed LTP-associated presynaptic changes require NMDA receptor activation, these data support models of LTP in which a retrograde messenger (generated subsequent to postsynaptic NMDA receptor activation) may produce presynaptic changes underlying LTP (36-38).. The mechanism by which LTP induction might lead to this ...
Introduction: The calcium/calmodulin-dependent kinase II (CaMKII) is activated by angiotensin-II, a strong inducer of vascular smooth muscle cell (VSM) hypertrophy. CaMKII activates HDAC4/MEF-2 dependent gene transcription by phosphorylation of HDAC4 S467 and 632. Here, we demonstrate that CaMKII mediates Ang-II-induced VSM hypertrophy in vitro and in vivo by activation of the HDAC4/MEF-2 signal transduction pathway.. Methods and Results: Medial hypertrophy by Ang-II infusion at pressor dose over 10 days was significantly reduced in C57Bl/6 mice when the CaMKII inhibitor KN93 was given daily i.p. (0.070 mm2 vs 0.052 mm2, p,0.05). In vitro, Ang-II increased the 3H-Leucine/3H-Thymidine uptake in control aortic VSM cells by 50% after 24 hr, whereas overexpression of the CaMKII peptide inhibitor CaMKIIN resulted only in 14 % increase (p,0.05). Ang-II induced phosphorylation of HDAC4 that was further increased under overexpression of CaMKIIδ2. CaMKII overexpression resulted in increased ...
Raval A, Tanner SM, Byrd JC, Angerman EB, Perko JD, Chen SS, Hackanson B, Grever MR, Lucas DM, Matkovic JJ, Lin TS, Kipps TJ, Murray F, Weisenburger D, Sanger W, Lynch J, Watson P, Jansen M, Yoshinaga Y, Rosenquist R, de Jong PJ, Coggill P, Beck S, Lynch H, de la Chapelle A, Plass C. Downregulation of death-associated protein kinase 1 (DAPK1) in chronic lymphocytic leukemia. Cell. 2007 Jun 01; 129(5):879-90 ...
Small molecule inhibitors of the human sirtuins and calmodulin-dependent protein kinases have shown promising anti-cancer activity in cell-based screens and animal models. We have synthesized analogues of these compounds, identifying more selective sirtuin inhibitors and more potent calmodulin-dependent protein kinase inhibitors.The sirtuins are a family of NAD+-dependent deacetylases that regulate cellular aging and gene silencing in simple organisms and appear to play important regulatory roles in human cells that make them attractive anti-cancer targets. We have previously identified the compound cambinol, an inhibitor of the human sirtuins SIRT1 and SIRT2, which is selectively toxic to Burkitts lymphoma cells. In order to determine which sirtuin is the relevant target, we screened analogues of cambinol, identifying compounds that exhibited moderate selectivity for both SIRT1 and SIRT2. The compound JP136 is ten-fold more selective in vitro for SIRT1 over SIRT2, with respective IC50s of 13 ...
This invention relates to the controlled release of calcium sulfate as well as to the controlled release of an additive to a calcium sulfate matrix such as medicaments or pesticides. The controlled release is achieved by a pellet comprising calcium sulfate. The pellet is prepared by the process comprising mixing powder consisting essentially of alpha-calcium sulfate hemihydrate, a solution comprising water, and, optionally, an additive and a powder consisting essentially of beta-calcium sulfate hemihydrate to form a mixture, and forming said mixture into a pellet, wherein said alpha-calcium sulfate hemihydrate and beta-calcium sulfate hemihydrate powders have specified properties such as BET surface areas, densities, mean particle sizes, and purifies. The dissolution rate of the calcium sulfate pellet is controlled by varying the weight ratio of the beta-calcium sulfate hemihydrate powder to the alpha-calcium sulfate hemihydrate powder from 0 to about 3. The invention also provides a method of
0071] The peptide hormone Ang II induces opening of mitochondrial KATP channels, depolarizes ΔΨm, and amplifies ROS generation from mitochondria [46]. We have shown that inhibition of CaMKII can protect against Ang II induced ROS species generation (FIG. 6). H9C2 cells and eventually neonatal cardiomyocytes from WT and mitoCaMKIIN mice will be cultured as described above, and peptide-loaded PLGA/PAMAM nanoparticles with and without surface bound MLS ligands will be prepared as described above. Cells will be treated with Ang II (1 μM for 3 hours). Both H9C2 cells and neonatal cardiomyocytes will be tested. We plan to isolate cardiomyocytes from four mouse litters of mitoCaMKIIN mice. Because these transgenic mice are crossed to WT-C57 mice each generation, the WT littermates will be used to test treated and untreated nanoparticles. A series of increasing doses of nanoparticles will be co-incubated with Ang II to determine the dose-response curve for generating protection against changes ...
Multiple calmodulin (CaM) isoforms are expressed in plants, but their biochemical characteristics are not well resolved. Here we show the differential regulation exhibited by two soya bean CaM isoforms (SCaM-1 and SCaM-4) for the activation of five CaM-dependent enzymes, and the Ca2+ dependence of their target enzyme activation. SCaM-1 activated myosin light-chain kinase as effectively as brain CaM (Kact 1.8 and 1.7nM respectively), but SCaM-4 produced no activation of this enzyme. Both CaM isoforms supported near maximal activation of CaM-dependent protein kinase II (CaM KII), but SCaM-4 exhibited approx.12-fold higher Kact than SCaM-1 for CaM KII phosphorylation of caldesmon. The SCaM isoforms showed differential activation of plant and animal Ca2+-ATPases. The plant Ca2+-ATPase was activated maximally by both isoforms, while the erythrocyte Ca2+-ATPase was activated only by SCaM-1. Plant glutamate decarboxylase was activated fully by SCaM-1, but SCaM-4 exhibited an approx. 4-fold increase ...
Background: Hypertensive cardiomyopathy or pathophysiological changes in myocardial structure and function caused by hypertension is a growing clinical problem due to the ageing population and a lack of curative therapies. The onset of the disease is often clinically silent, progressing over time to therapy-resistant symptomatic forms. Existing therapeutic concepts are, therefore, symptom-oriented and tailored for advanced stages of cardiac remodeling. Understanding molecular processes driving early hypertension-induced changes may improve diagnosis and treatment options.. Recent evidence positions changes in Ca2+ cycling as an early promoter of cardiac remodeling via Ca2+-mediated regulation of transcription. The enzyme Ca2+/calmodulin-dependent protein kinase II (CaMKII) has a central role in this process, as it can translate fine changes in Ca2+ fluxes into altered gene expression. However, the specific regulation of this so-called excitation-transcription coupling in hypertensive ...
Heart failure stays a significant well being burden around the globe. Despite nice progress in delineation of molecular mechanisms underlying growth of illness, normal remedy has not superior on the similar tempo. The multifunctional signaling molecule Ca2+/calmodulin-dependent protein kinase II (CaMKII) has acquired appreciable consideration over current years for its central function in maladaptive reworking and arrhythmias … Read more. ...
We use Drosophila melanogaster for studying cardiac diseases. One transgenic strain containing a fluorescent reporter system that senses intracellular twitch Ca2+ transient increases was utilized. We observed changes in the frequency of Ca2+ transients with age in semi-intac fly heart preparations and its putative modification by 1) The inhibition of Ca2+-calmodulin-dependent protein kinase (CaMKII), involved in Ca2+ cycling and 2) the reduction in eIF4E expression, an eukaryotic translation initiation factor. Results: Flies between 60 and 70 days old showed reduction of heart rate compared with 7 days old flies and widespred distribution of cardiac periods (intervals between transient increases of Ca2+). Arrhythmicity index (standard deviation of the heart period), increased from 0.27 to 0.52 (n=12). CaMKII inhibition reduced dispersion of cardiac periods distribution and arrhythmicity index from 0.27 to 0.19 (n = 21). Lower levels of eIF4E reduced dispersion of cardiac periods distribution and ...
Our laboratory identified CaMKII as an important pro-arrhythmic and pro-cardiomyopathic signal. Our work has provided proof of concept evidence motivating active efforts in biotech and the pharmaceutical industry to develop therapeutic CaMKII inhibitory drugs to treat heart failure and arrhythmias. My group discovered that CaMKII is activated by oxidation and excessive CaMKII activity participates in cellular injury in response to diverse upstream signals, including the renin-angiotensin-aldosterone pathway and endotoxin by oxidative activation. CaMKII is multifunctional because it has multiple downstream targets. CaMKII catalyzed phosphorylation of diverse proteins in myocardium appears to coordinate activity of many or most voltage-gated ion channels, Ca2+ homeostatic proteins and gene transcription. Under physiological conditions, CaMKII is important for excitation-contraction coupling and fight or flight heart rate increases. However, myocardial CaMKII is excessively activated during ...
Structural and biophysical studies reveal how CaMKII kinases, which are important for cellular learning and memory, are switched on by binding of Ca2+/calmodulin.
Recombinant full-length human CAMK4 was expressed by baculovirus in Sf9 insect cells using an N-terminal GST tag. CAMK4 is a multifunctional serine/threonine protein kinase and a member of Ca2+/calmodulin-dependent protein kinase family.
Roles of calmodulin and CaMKII in mediating PKG stimulation of Kir6.2/SUR2A channels.Recombinant Kir6.2/SUR2A channels were expressed in HEK293 cells by transie
There are no specific protocols for CaMKII alpha (phospho T286) peptide (ab115237). Please download our general protocols booklet
マウス・モノクローナル抗体 ab54925 交差種: Hu 適用: WB,IP,Flow Cyt,ICC/IF…CaMKII alpha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 製品。国内在庫と品質保証制度も充実。
Recombinant Calcium/calmodulin-Dependent Protein Kinase IV (CAMK4) Protein (His tag). Spezies: Human. Quelle: Escherichia coli (E. coli). Jetzt Produkt ABIN668012 bestellen.
To elucidate mechanisms that control and execute activity-dependent synaptic plasticity, α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPA-Rs) with an electrophysiological tag were expressed in rat hippocampal neurons. Long-term potentiation (LTP) or increased activity of the calcium/calmodulin-dependent protein kinase II (CaMKII) induced delivery of tagged AMPA-Rs into synapses. This effect was not diminished by mutating the CaMKII phosphorylation site on the GluR1 AMPA-R subunit, but was blocked by mutating a predicted PDZ domain interaction site. These results show that LTP and CaMKII activity drive AMPA-Rs to synapses by a mechanism that requires the association between GluR1 and a PDZ domain protein. ...
Results We show that culture of MRL/lpr Foxp3-GFP T cells in the presence of KN-93 promotes Treg differentiation in a dose dependent manner (Fig. F). Treatment of MRL/lpr Foxp3-GFP mice with KN-93 results in significant induction of Treg cells in the spleen, peripheral lymph nodes (Fig. B-E) and peripheral blood (Fig. A and B) and this is accompanied by decreased skin and kidney damage. Notably, KN-93 clearly diminishes the accumulation of inflammatory cells along with reciprocally increased Treg cells in target organ.. ...
Background: CaMKK β is a major kinase activated by elevated levels of intracellular calcium. Our previous data has suggested that CaMKK β is neuroprotective after stroke in young mice as inhibition of this kinase aggravated stroke outcome. As aging is an important determinant of stroke outcomes, here we evaluated the functional role of CaMKK β in stroke in aged mice.. Methods: Aged wild type (WT) males received intracerebral injections of lentiviral vectors carrying either CaMKK β (LV-CaMKK β) or GFP (LV-GFP) 7 days before middle cerebral artery occlusion (MCAO, 90 minutes). Acute infarcts and neurological deficits scores were then analyzed at 72 hours post MCAO. In chronic survival studies, aged male CaMKK β knockout (KO) and WT mice were subjected to 60 minutes MCAO. Following stroke, long-term behavioral assessments were continuously performed for 3 weeks in KO and WT mice until the sacrifice for tissue loss assessments.. Results: Baseline levels of CaMKK β in aged brain were ...
Objective: Sucralose, a high-intensity sweetener, has been approved as a general-purpose sweetener in all food since the late 1990s. Due to its good taste and physiochemical profile, its use has increased and sucralose is considered a way of managing health and an option to improve the quality of life in the diabetic population. Recently high concentrations of sucralose have been found in the environment. Other environmental pollutants have been shown to induce neurotoxic effects when administered during a period of rapid brain growth and development. This period of rapid brain growth and development is postnatal in mice and rats, spanning the first 3-4 wk of life, reaching its peak around postnatal day 10, whereas in humans, brain growth and development is perinatal. The proteins calcium/calmodulin-dependent protein kinase II, growth-associated protein-43, synaptophysin, and tau play important roles during brain growth and development.. Methods: In the present study, mice were orally exposed to ...
Objective To evaluate the impact of miR-148a on hepatic ischemia/reperfusion (I/R) injury via inhibiting Ca(2+)/calmodulin-dependent protein kinase IIα (CaMKIIα), and analyze the potential mechanism. Methods Liver I/R model was built in mice. Expression of CaMKIIα was detected in the hepatic tissues by Western blotting. The mRNA levels of miR-148a, CaMKIIα, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were analyzed by quantitative real-time PCR (qRT-PCR). HE staining was performed to observe morphological changes of the livers in each group. TUNEL was used to evaluate the degree of hepatocellular apoptosis in each group. Results After hepatic I/R injury, the expression of miR-148a increased, and it was negatively correlated with CaMKIIα. After therapy with exogenous miR-148a mimics, the protein expression of CaMKIIα, the mRNA levels of TNF-α and IL-1β, the degree of inflammatory cell infiltration and liver cell necrosis, and the level of hepatocellular apoptosis were all
Osteosarcoma is among the most frequently occurring primary bone tumors, primarily affecting adolescents and young adults. Despite improvements in osteosarcoma treatment, more specific molecular targets are needed as potential therapeutic options. One target of interest is α-Ca2+/calmodulin-dependent protein kinase II (α-CaMKII), a ubiquitous mediator of Ca2+-linked signaling, which has been shown to regulate tumor cell proliferation and differentiation. Here, we investigate the role of α-CaMKII in the growth and tumorigenicity of human osteosarcoma. We show that α-CaMKII is highly expressed in primary osteosarcoma tissue derived from 114 patients, and is expressed in varying levels in different human osteosarcoma (OS) cell lines [MG-63, N-methyl-N′-nitro-N-nitrosoguanidine (MNNG)/HOS, and 143B). To examine whether α-CaMKII regulates osteosarcoma tumorigenic properties, we genetically inhibited α-CaMKII in two osteosarcoma cell lines using two different α-CaMKII shRNAs delivered by ...
Muscle differentiation is activated by the transcription factor MEF2, which interacts with other transcriptional regulators such as MyoD to promote myogenesis and with histone deactylases (HDAC4 and HDCA5) to inhibit myogenesis. In order for MEF2 to promote myogenesis, there must be a mechanism to shift the balance of these two interactions. McKinsey et al. found that the subcellular distribution of HDAC5 changes from nuclear to cytoplasmic during skeletal muscle differentiation in culture. In transfected Cos cells, activation of calcium-calmodulin kinase (CaMK) I, but not the mitogen-activated protein kinases MKK6, MEK5, or ERK5, or the phosphatase calcineurin, was able to cause the redistribution of HDAC5. Thus, the CaMKI pathway appears to be specific for regulating HDAC, whereas the other MEF2 activators act through a different mechanism. (Stewart and Crabtree describe how the pathways may converge to promote myogenesis.) HDAC5 is phosphorylated in multiple locations by CaMKIV, and the ...
Within the compact cilia of the olfactory receptor neurons (ORNs) a cascade of enzymatic activity transduces the binding of an odorant molecule to a receptor into an electrical signal that can be transmitted to the brain. Odorant molecules bind to a receptor protein (R) coupled to an olfactory specific Gs-protein (G) and activate a type III adenylyl cyclase (AC), increasing intracellular cAMP levels. cAMP targets an olfactory-specific cyclic-nucleotide gated ion channel (CNG), allowing cations, particularly Na and Ca, to flow down their electrochemical gradients into the cell, depolarizing the ORN. Furthermore, the Ca entering the cell is able to activate a Ca-activated Cl channel, which would allow Cl to flow out of the cell, thus further increasing the depolarization. Elevated intracellular Ca causes adaptation by at least two different molecular steps: inhibition of the activity of adenylyl cyclase via CAMKII-dependent phosphorylation and down-regulation of the affinity of the CNG channel to ...
Full Text - Ligands of nicotinic acetylcholine receptors (nAChRs) are widely considered as potential therapeutic agents. The present study used primary hippocampus cells and APPswe/PSEN1dE9 double-transgenic mice models to study the possible therapeutic effect and underlying mechanism of the specific activation of α7 nAChR by PNU-282987 in the pathogenesis of Alzheimer’s disease. The results indicated that activation of α7 nAChR attenuated the Aβ-induced cell apoptosis, decreased the deposition of Aβ, increased the expression of synaptic-associated proteins, and maintained synaptic morphology. Furthermore, in the APP/PS1_DT mice model, activation of α7 nAChR attenuated Aβ-induced synaptic loss, reduced the deposition of Aβ in the hippocampus, maintained the integral structure of hippocampus-derived synapse, and activated the calmodulin (CaM)-calmodulin-dependent protein kinase II (CaMKII)-cAMP response element-binding protein signaling pathway by
After completing medical school and internal medicine training at the University of Missouri, Dr. Gorelick trained at Yale in Gastroenterology. After his clinical training, he began basic science training with Dr. James Jamieson at Yale. During that period he described calcium-calmodulin dependent protein kinase II and
Song, S. H., & Augustine, G. J. (2016). Synapsin isoforms regulating GABA release from hippocampal interneurons. The Journal of Neuroscience, 36(25), 6742-6757. PMID: 27335405. Wahba, G., Hebert, A. E., Grynspan, D., Staines, W., & Schock, S. (2016). A rapid and efficient method for dissociated cultures of mouse myenteric neurons. Journal of neuroscience methods, 261, 110-116. PMID: 26706461. Magupalli, V. G., Mochida, S., Yan, J., Jiang, X., Westenbroek, R. E., Nairn, A. C., Scheuer, T. & Catterall, W. A. (2013). Ca2+-independent activation of Ca2+/calmodulin-dependent protein kinase II bound to the C-terminal domain of CaV2. 1 calcium channels. Journal of Biological Chemistry, 288(7), 4637-4648. PMID: 23255606. Kurtis D. Davies, Susan M. Goebel-Goody, Steven J. Coultrap, and Michael D. Browning (2008) Long Term Synaptic Depression That Is Associated with GluR1 Dephosphorylation but Not-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA)Receptor Internalization J. Biol. Chem., 283: 33138 ...
Walikonis, Randall S. and Oguni, Asako and Khorosheva, Eugenia M. et al. (2001) Densin-180 forms a ternary complex with the α-subunit of Ca^(2+)/calmodulin-dependent protein kinase II and α-actinin. Journal of Neuroscience, 21 (2). pp. 423-433. ISSN 0270-6474. PMCID PMC6763799. https://resolver.caltech.edu/CaltechAUTHORS:20120424-150007753 ...
All living cells require energy, usually provided in the form of ATP, to carry out fundamental processes like movement and growth. Therefore, cells have to balance energy supply with the demand. AMP-activated protein kinase (AMPK) has emerged as a central component of a signalling pathway involved in regulating intracellular energy homeostasis. When ADP and AMP levels increase, concomitant with a fall in ATP levels, AMPK is activated by phosphorylation on threonine-172 within the catalytic a subunit by upstream kinases including LKB1 and calcium/calmodulin protein kinase kinase (CaMKK) ß. Once activated, AMPK responds by phosphorylating downstream targets, the net effect of which is to switch off ATP-consuming processes and switch on ATP-producing processes. When the levels of nucleotides are restored to normal physiological concentrations, AMPK is inactivated by an unknown protein phosphatase(s). Major advances have been made over the last five years in understanding the molecular mechanism of how
Journal of Diabetes Research is a peer-reviewed, Open Access journal that publishes research articles, review articles, and clinical studies related to type 1 and type 2 diabetes. The journal welcomes submissions focusing on the epidemiology, etiology, pathogenesis, management, and prevention of diabetes, as well as associated complications, such as diabetic retinopathy, neuropathy and nephropathy.
Assistant: Margot Hoyt. While working on the crystal structure of the 250-kDa Ca2+-calmodulin-dependent kinase II (CaMKII) core in John Kuryan s laboratory, André developed a strong fascination for macromolecular assemblies. Inspired by the large CaMKII structure, André joined Günter Blobel s laboratory with the idea of starting a comprehensive structural and functional characterization of the ~120 million Dalton nuclear pore complex (NPC), one of the largest proteinaceous assemblies in eukaryotic cells. In Günter Blobel s laboratory André set up a structural biology subgroup that established the NPC as a viable target for an interdisciplinary divide-and-conquer approach, employing X-ray crystallographic, biochemical and in vivo studies, funded by a grant from the Leukemia and Lymphoma Society. Simultaneously, André stared a second line of research on the regulation of the histone-modifying machinery. André joined the Caltech faculty in November 2010.. The Hoelz lab carries out ...
5-(4-chlorobenzoyl)amino-N-(4-chlorophenyl)-N-methyl-3-methyl-4-isothiazolecarboxamide: Anti-Inflammatory Agents, Non-Steroidal; structure in first source
biomat has developed a polystyrene surface with physically adsorbed Calmodulin protein. The Calmodulin Ca ++ binding protein is able to bind proteins mainly with hydrophobic sites in its surface.. The polystyrene optical features dont change, allowing the modified surface to be used as a valid tool to carry out biological tests.. This surface shows its usefulness for these applications:. ...
RecName: Full=Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma; EC=2.7.1.149;AltName: Full=Phosphatidylinositol 5-phosphate 4-kinase type II gamma; Short=PI(5)P 4-kinase type II gamma; Short=PIP4KII-gamma ...
Dr. Zaijie Jim Wang and colleagues at the University of Illinois suppressed morphine tolerance and dependence in mice by blocking calcium/calmodulin-dependent protein kinase II (CaMKII), which may contribute to chronic pain in the central nervous system. In a followup study, the investigators found elevated levels of CaMKII activity in the brain and spinal cord (an 81 percent and 222 percent increase, respectively) of mice displaying morphine tolerance compared with mice that did not. Trifluoperazine, an antipsychotic drug and a CaMKII inhibitor newly identified by these researchers, prevented both the increase in CaMKII activity and the development of opioid tolerance and disrupted established opioid tolerance in the animals. The findings suggest that CaMKII-suppressing drugs may reduce morphine tolerance and ultimately be of value in treating pain and fighting opioid addiction.. Neuroscience Letters 397(1-2):1-4, 2006; [Abstract ...
P164 Angiotensin II (Ang II) promotes arachidonic acid (AA) release via activation of cytosolic phospholipase A2 (cPLA2) and D (PLD) in rabbit vascular smooth muscle cells (VSMC). Ang II also stimulates the Ras/MAP kinase pathway, and MAP kinase activates cPLA2 and PLD in VSMC. The increase in Ras/MAP kinase activity elicited by Ang II in VSMC is mediated by 20-hydroxyeicosatetraenoic acid (HETE) and to a lesser extent by 12(S)-HETE, metabolites of AA generated by cytochrome P450 (CYP) and lipoxygenase (LO), respectively, upon activation of cPLA2 by calcium calmodulin-dependent kinase II. The purpose of this study was to determine if Ang II-induced PLD activation stimulation in VSMC from rabbit aorta is mediated by the Ras/MAP kinase pathway via AA metabolites generated by cPLA2. Ang II (100 nM) increased PLD activity measured as the production of 3H-phosphatidylethanol from phospholipids in VSMC prelabeled with 3H-oleic. Inhibitors of PLD (C2-ceramide, 10 μM), phosphatidate phosphohydrolase ...
The results of the present study identify the ERK 1/2 MAP kinase as being responsible for phosphorylation of eNOS at Ser116 in endothelial cells under basal conditions. Ser116 phosphorylation has been shown previously by Kou et al to be reduced by the protein kinase C (PKC) inhibitor calphostin C, implicating PKC as a mediator of this specific phosphorylation reaction.21 However, Shaw and colleagues22,23 have recently shown that the AGC kinases (protein kinase A, protein kinase G, and PKC), as well as the calmodulin-dependent protein kinases, cannot phosphorylate serines or threonines in protein substrates containing a proline at the P+1 position. Proline at P+1 is thus a "veto residue" that precludes phosphorylation by AGC and calmodulin-dependent protein kinases. This feature of proline-directed phosphorylation provides very tight control in preventing reciprocal substrate specificity between proline-directed protein kinases and AGC/calmodulin-dependent protein kinases. Because Ser116 in the ...
Purpose: : During NMDA-induced cell death in the neural retina, there is an elevation of the nuclear isoform of CaMKIIα (CaMKIIαB). This result leads to the question of how CaMKIIαB might be involved in either a cell death or cell survival pathway, for example, in retinal ganglion cells (RGCs). The purpose of this study is to investigate if CaMKIIα regulates BDNF expression in RGCs. Methods: : Highly purified RGCs or dissociated retinal cells were obtained from P6-8 SD rat eyes and treated with glutamate (200-1000uM) for the indicated times. Glutamate cytotoxicity on RGCs and localization of CaMKIIα was determined by cell counting and immunostaining, respectively. To identify the role of CaMKIIα in regulating BDNF expression, CaMKIIαB expression vector was constructed and over-expressed in cells of the RGC-5 cell line, and cell viability was assayed. Specific siRNAs to knock down CaMKIIαB or CaMKIIα were then tested in CaMKIIαB-transfected or non-transfected RGC-5 cells. The siRNAs ...
TY - JOUR. T1 - Reduced activation of intracellular signaling pathways in rat prefrontal cortex after chronic phencyclidine administration. AU - Molteni, Raffaella. AU - Pasini, Matteo. AU - Moraschi, Stefania. AU - Gennarelli, Massimo. AU - Drago, Filippo. AU - Racagni, Giorgio. AU - Riva, Marco A.. PY - 2008/4. Y1 - 2008/4. N2 - Evidence exists that schizophrenia is characterized by deficits in cell-cell communication and information processing. In the present study, we used the phencyclidine (PCP) animal model of schizophrenia to investigate possible defects in intracellular signaling proteins involved in neuroplasticity. Western Blot analysis has been performed to determine total and phospho-protein levels of extracellular signal-regulated kinases 1/2 (ERK1/2), type II calcium/calmodulin-dependent protein kinase (αCaMKII) and cAMP-response element binding protein (CREB) in prefrontal cortex (PFC) and hippocampus (HIP) of rat chronically treated with PCP, whereas their mRNA levels were ...
Adunyah S.E.; Dean W.L., 1987: Regulation of human platelet membrane calcium transport by cyclic amp and calmodulin dependent phosphorylation
The IUPHAR/BPS Guide to Pharmacology. casein kinase II inhibitor III ligand page. Quantitative data and detailed annnotation of the targets of licensed and experimental drugs.
In both cardiac and slow-twitch skeletal muscle sarcoplasmic reticulum (SR) there are several systems involved in the regulation of Ca2+-ATPase function. T
Synaptic activity triggers a profound reorganization of the molecular composition of excitatory synapses. GluN2B/CaMKII binding reduces synapse number it increases synaptic-GluN2B content. Therefore the GluN2B/CaMKII association controls synapse density and PSD composition in an activity-dependent manner including recruitment of CK2 to remove GluN2B from synapses. NSC 687852 INTRODUCTION The molecular composition of the postsynaptic density (PSD) at excitatory synapses is profoundly modified in response to synaptic activity including changes in receptors scaffolding proteins and signaling enzymes (Ehlers 2003 Glutamate receptors are important constituents of PSDs and the dynamic regulation of their synaptic expression is a central mechanism for modulating the strength of excitatory neurotransmission. Therefore glutamate receptors are subject to strict controlling mechanisms that allow both short- and long-term modifications in their number localization and composition in a cell- and ...
The files in this directory incorporate calcium handling mechanisms involved in the Ca - Calmodulin - CaMKII - PP1 pathway in a conductance-based neuronal CA1 pyramidal model developed in Rathour and Narayanan, PNAS, 2014. The simulation environment is NEURON. The model contains Na, KDR, KA, h, CaT and CaR currents, and employs GHK-based implementations of AMPA and NMDA receptors. Fig13.hoc helps recreate Fig 13 of the following paper: Basak R, Narayanan R. Active dendrites regulate the spatiotemporal spread of signaling microdomains; Plos Comp Biol (in Press). Running Fig13.hoc will create files that will contain .txt files storing the values of various species (Ca, Calmodulin, phosphorylated CaMKII etc.) as they evolve with time at various spatial locations, specifically the 100 µm length around the spine-containing synapse in the oblique containing the calcium handling mechanisms. The default number of spines in the oblique in the .hoc file is 1000. Example output was obtained by running the ...
The product of this gene belongs to the Serine/Threonine protein kinases family, and to the Ca(2+)/calmodulin-dependent protein kinases subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic synapses. This enzyme is composed of four different chains: alpha, beta, gamma, and delta. The alpha chain encoded by this gene is required for hippocampal long-term potentiation (LTP) and spatial learning. In addition to its calcium-calmodulin (CaM)-dependent activity, this protein can undergo autophosphorylation, resulting in CaM-independent activity. Two transcript variants encoding distinct isoforms have been identified for this gene ...
(±)-4-Amino-N-1-azabicyclo[2.2.2]oct-3-yl-5-chloro-2-methoxybenzamidehydrochloride chemical properties, What are the chemical properties of (±)-4-Amino-N-1-azabicyclo[2.2.2]oct-3-yl-5-chloro-2-methoxybenzamidehydrochloride 90182-92-6, What are the physical properties of (±)-4-Amino-N-1-azabicyclo[2.2.2]oct-3-yl-5-chloro-2-methoxybenzamidehydrochloride ect.
Atherosclerosis is the underlying etiology of cardiovascular disease, the leading cause of death worldwide. Atherosclerosis is a heterogeneous disease in which only a small fraction of lesions lead to heart attack, stroke, or sudden cardiac death. A distinct type of plaque containing large necrotic cores with thin fibrous caps often precipitates these acute events. Here, we show that Ca2+/calmodulin-dependent protein kinase γ (CaMKIIγ) in macrophages plays a major role in the development of necrotic, thin-capped plaques. Macrophages in necrotic and symptomatic atherosclerotic plaques in humans as well as advanced atherosclerotic lesions in mice demonstrated activation of CaMKII. Western diet-fed LDL receptor-deficient (Ldlr-/-) mice with myeloid-specific deletion of CaMKII had smaller necrotic cores with concomitantly thicker collagen caps. These lesions demonstrated evidence of enhanced efferocytosis, which was associated with increased expression of the macrophage efferocytosis receptor ...
As mentioned above, RyRs are often complexed with several accessory proteins, forming an intricate multi-protein array [32, 33]. The best known RyR-interacting proteins are CaM, which tonically inhibits RyR2 activity and produces biphasic effects on RyR1 [34, 35]; FKBP12 and FKBP12.6, which stabilize RyR1 and RyR2 closures [36-38]; and the ternary complex triadin-junctin-calsequestrin, which senses luminal Ca2+ content and modulates RyR activity by acting either as a Ca2+ reservoir or as a direct channel ligand [39-47]. More recently, RyR2 has been found to hold anchoring sites for protein kinase (PK)A, protein phosphatase (PP)1, the cAMP-specific phosphodiesterase (PDE)4D3 and Ca2+/calmodulin-dependent protein kinase (CaMK)II [37, 48], emphasizing the importance of RyR2 regulation by phosphorylation [32]. In cardiac cells, sorcin exerts protein-protein interactions with the RyR and inhibits Ca2+ release in a Ca2+-dependent manner [49, 50].. The binding sites of several regulatory proteins ...
Songyang Z, Lu KP, Kwon YT, Tsai LH, Filhol O, Cochet C, Brickey DA, Soderling TR, Bartleson C, Graves DJ, Demaggio AJ, Hoekstra MF, Blenis J, Hunter T, Cantley LC. A structural basis for substrate specificities of protein ser/thr kinases-primary sequence preference of casein kinases I and II, NIMA, phosphorylase kinase, calmodulin-dependent kinase II, Cdk5 and ERK1. Mol Cell Biol 1996;16:6486-93 ...
C_horizon,C horizon]]:-> [[parent_rock,parent rock]]:母岩 ;[[C-value_paradox,C-value paradox]]: ;[[C3_pathway,C3 pathway (C,sub>3,/sub> pathway)]]:C3経路 ;[[C3_plant,C3 plant(s) [C,sub>3,/sub> plant(s)]]]:C3植物 ;[[C4_pathway,C4 pathway (C,sub>4,/sub> pathway)]]:C4経路 ;[[C4_photosynthesis,C4 photosynthesis (C,sub>4,/sub> photosynthesis)]] ;[[C4_plant,C4 plant(s) [C,sub>4,/sub> plant(s)]]]:C4植物 === Ca === ;[[Ca2+/calmodulin-dependent_protein_kinase , Ca,sup>2+,/sup>/calmodulin-dependent protein kinase]]:->[[CaM-kinase]] ;cactus:サボテン,サボテン類 ==== Cad ==== ;[[cadherin]]:カドヘリン ;[[caducous]]: ==== Cae ==== ;[[Caenorhabditis_elegans , Caenorhabditis elegans]]: ==== Cag ==== ;[[caged_molecule,caged molecule]]: ==== Cak ==== ;[[CAK]]:->[[Cdk-activating_kinase , Cdk-activating kinase]] ==== Cal ==== ;[[calcitonin]]: ;[[calcium_pump,calcium pump]]:->[[Ca2+_pump , Ca,sup>2+,/sup> pump]] ;[[calcrete,calcrete (caliche)]]: ;caliche:-> [[calcrete,calcrete]] ...
30194-69-5 - STFKGUOQAKLRFA-UHFFFAOYSA-N - Benzamide, 4-amino-N-(2-(4-(3,3-diphenylpropyl)-1-piperazinyl)ethyl)-, hydrochloride, hydrate (1:3:2) - Similar structures search, synonyms, formulas, resource links, and other chemical information.
Background CALM2 is the second calmodulin gene. Although the CALM1,CALM2, and CALM3 calmodulin proteins are identical, at the nucleotide level they share only about 80% identity within their coding regions, and they contain...
Plasmid pDONR223-CAMK1G from Dr. William Hahns lab contains the insert CAMK1G and is published in Nature. 2010 Nov 24. ():. This plasmid is available through Addgene.
Looking for online definition of CaM-kinase II alpha chain in the Medical Dictionary? CaM-kinase II alpha chain explanation free. What is CaM-kinase II alpha chain? Meaning of CaM-kinase II alpha chain medical term. What does CaM-kinase II alpha chain mean?
The metabolic sensor, AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase existing as a heterotrimer of catalytic (α1/α2) and regulatory subunits (β1/β2 and γ1/γ2/γ3). The 12 possible heterotrimers exhibit tissue and potentially functional specificity [8], and all can be activated by binding of AMP/ADP to the AMPKγ subunit and phosphorylation by one of two upstream kinases, liver kinase B (LKB)1 or calcium/calmodulin-dependent protein kinase kinase (CaMKK)β. AMPK is activated in response to depletion of ATP or alterations in intracellular calcium concentrations, and acts to shut down ATP-consuming, anabolic pathways and promoting ATP-generating, catabolic pathways [9].. As a monitor of cellular and whole body energy status [10], it is probably unsurprising that a recent elegant study in Science from Reuben Shaws laboratory places AMPK at the heart of the regulation of mitochondrial dynamics. Using CRISPR modification to delete AMPKα1 and/or AMPKα2 in vitro, they ...
Neonatal hypoxia-ischemia (HI) is a major cause of death and disability in neonates. HI leads to a dramatic rise in intracellular calcium levels, which was originally thought to be detrimental to the brain. However, it has been increasingly recognized that this calcium signaling may also play an important protective role after injury by triggering endogenous neuroprotective pathways. Calcium/calmodulin-dependent protein kinase kinase ß (CaMKK ß) is a major kinase activated by elevated levels of intracellular calcium. Here we evaluated the functional role of CaMKK ß in neonatal mice after HI in both acute and chronic survival experiments. Postnatal day ten wild-type (WT) and CaMKK ß knockout (KO) mouse male pups were subjected to unilateral carotid artery ligation, followed by 40 min of hypoxia (10% O2 in N2). STO-609, a CaMKK inhibitor, was administered intraperitoneally to WT mice at 5 minutes after HI. TTC (2,3,5-triphenyltetrazolium chloride monohydrate) staining was used to assess ...
Calcium/calmodulin-dependent kinase kinase 2 (CaMKK2) has been implicated in a range of conditions and pathologies from prostate to hepatic cancer. Here, we describe the expression in Escherichia coli and the purification protocol for the following constructs: full-length CaMKK2 in complex with CaM, CaMKK2 apo, CaMKK2 (165-501) in complex with CaM, and the CaMKK2 F267G mutant. The protocols described have been optimized for maximum yield and purity with minimal purification steps required and the proteins subsequently used to develop a fluorescence-based assay for drug binding to the kinase, Using the fluorescent properties of STO-609 as a tool to assist structure-function analyses of recombinant CaMKK2 [1].
US Patent 9,168,307 Mitochondrial-targeted cationic nanoparticles comprising CaMKII inhibitors and uses thereof for treating and preventing diseases and disorders associated with CaMKII activity, Mark E Anderson, Mei-ling A Joiner, Aliasger K Salem, Amaraporn Wongrakpanich, Frederick E Domann, Duane D Hall, Olha M Koval, and Douglas R Spitz. ...
... by protein kinase C and calcium/calmodulin kinase II in vitro". J. Neurochem. 71 (3): 1307-14. doi:10.1046/j.1471-4159.1998. ... Kubes M, Cordier J, Glowinski J, Girault JA, Chneiweiss H (1998). "Endothelin induces a calcium-dependent phosphorylation of ... "Molecular characterization of the human PEA15 gene on 1q21-q22 and association with type 2 diabetes mellitus in Pima Indians". ... "Protein kinase B/Akt binds and phosphorylates PED/PEA-15, stabilizing its antiapoptotic action". Mol. Cell. Biol. 23 (13): 4511 ...
... interleukin-1 receptor accessory protein-like 1 protein) PI4KIIIβ (type III phosphatidylinositol 4-kinase β) IP3 receptor (this ... PIK1 It binds to many proteins, some in calcium dependent and some in calcium independent ways, and switches many of the ... calcium-binding protein. Frq can substitute for calmodulin in some situations. It is thought to be associated with neuronal ... NCS-1 is a member of the neuronal calcium sensor family, a class of EF hand containing calcium-myristoyl-switch proteins. NCS-1 ...
Ca2+/calmodulin-dependent protein kinase II (CaMK II) is also activated by calcium influx through NMDA receptors, and is ... Lacosamide is used in combination with other types of medications to control various types of seizures, especially epilepsy. ... and cyclin-dependent protein kinase 5 (Cdk5) are highly expressed in Alzheimer's disease and are some of the protein kinases ... revealing the presence of both Rho kinase-dependent and Rho kinase-independent pathways for the growth cone collapse. In RhoA ...
... p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II and alpha-actinin-1 in a calcium-dependent ... 2004). "Regulation of type 1 protein phosphatase/inhibitor-2 complex by glycogen synthase kinase-3beta in intact cells". J. ... p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II and alpha-actinin-1 in a calcium-dependent ... Agarwal-Mawal A, Paudel HK (2001). "Neuronal Cdc2-like protein kinase (Cdk5/p25) is associated with protein phosphatase 1 and ...
... calcium/calmodulin-dependent protein kinase IV, and the peroxisome proliferator γ coactivator 1 (PGC-1). The Ras/MAPK signaling ... Calcineurin, a Ca2+/calmodulin-activated phosphatase implicated in nerve activity-dependent fiber-type specification in ... proteins and other regulatory proteins. Ca2+/calmodulin-dependent protein kinase activity is also upregulated by slow motor ... calcineurin and calcium/calmodulin-dependent protein kinase IV to activate transcription factors that regulate gene expression ...
Calcium-Calmodulin Dependent Protein Kinases at the US National Library of Medicine Medical Subject Headings (MeSH) To learn ... Erondu, N.E., and Kennedy, M.B. (1985). Regional distribution of type II Ca2+/calmodulin-dependent protein kinase in rat brain ... Ca2+ /calmodulin-dependent protein kinase II (CaM kinase II or CaMKII) is a serine/threonine-specific protein kinase that is ... Calcium/ calmodulin dependent protein kinase II is also heavily implicated in long-term potentiation (LTP) - the molecular ...
... neural protein contains phosphorylation sites for cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase ... Lack of synapsins altogether in neurons, leads to behavioral alterations as well as epileptic-type seizures. The lack affects ... and domain B has two mitogen-activated protein kinase phosphorylation sites. At its B domain, between amino acids 43 and 121, ... The synapsin II protein has been shown to interact with SYN1. Mutations in the SYN2 gene may be associated with abnormal ...
Zhang S, Ehlers MD, Bernhardt JP, Su CT, Huganir RL (August 1998). "Calmodulin mediates calcium-dependent inactivation of N- ... ". "Protein Information - Basic Information: Protein COPaKB ID: P35609". Cardiac Organellar Protein Atlas Knowledgebase. Zong ... Young P, Ferguson C, Bañuelos S, Gautel M (March 1998). "Molecular structure of the sarcomeric Z-disk: two types of titin ... "Interactions of calmodulin and alpha-actinin with the NR1 subunit modulate Ca2+-dependent inactivation of NMDA receptors". The ...
... calcium/calmodulin-dependent serine protein kinase 3 and membrane-associated guanylate kinase 2. This gene is located on the ... Hsueh YP, Roberts AM, Volta M, Sheng M, Roberts RG (June 2001). "Bipartite interaction between neurofibromatosis type I protein ... "Entrez Gene: CASK Calcium/calmodulin-dependent serine protein kinase (MAGUK family)". Tarpey PS, Smith R, Pleasance E, Whibley ... Zhu ZQ, Wang D, Xiang D, Yuan YX, Wang Y (2014). "Calcium/calmodulin-dependent serine protein kinase is involved in exendin-4- ...
Calcium/calmodulin-dependent protein kinase type IV is an enzyme that in humans is encoded by the CAMK4 gene. The product of ... calmodulin-dependent protein kinase I by calmodulin and by Ca2+/calmodulin-dependent protein kinase kinase". J. Biol. Chem. 273 ... Phosphorylation by cyclic AMP-dependent protein kinase, protein kinase C, and calcium/calmodulin protein kinase; identification ... and activation of Ca2+-calmodulin-dependent protein kinase IV by Ca2+-calmodulin-dependent protein kinase Ia kinase. ...
... and a calcium/calmodulin-dependent kinase (CAMK-1), and additional kinases, reaching its peak around mid-subjective day. Kinase ... with just one of the proteins present. The choice of which protein is made is the result of temperature-dependent splicing of ... Because sFRQ favors a longer period than lFRQ, free running rhythms in wild type Neurospora are somewhat decreased with ... A similar palette of kinases modifies the clock proteins in all cases. White Collar-1 Colin Pittendrigh Period (gene) Casein ...
This calcium then interacts with calcineurin and calcium/calmodulin-dependent kinases that in turn activate transcription ... Ozcan, U. (2004). "Endoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes". Science. 306 (5695): 457- ... "Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1". Science. 287 (5453): ... PERK (protein kinase RNA-like endoplasmic reticulum kinase) activates itself by oligomerization and autophosphorylation of the ...
The δ subunit is the ubiquitous eukaryotic protein calmodulin which itself has 4 calcium ion binding sites. When cytosolic Ca2+ ... but phosphorylation of both these subunits by protein kinase A (PKA, or cAMP-dependent protein kinase) reduces their respective ... Defects in phosphorylase kinase genes are the cause of glycogen storage disease type IX (GSD type IX) and GSD type VI (formerly ... In the active site, there is significant homology between PhK and other so-called P-loop protein kinases such as protein kinase ...
Calcium/calmodulin-dependent protein kinase type II gamma chain is an enzyme that in humans is encoded by the CAMK2G gene. The ... "Entrez Gene: CAMK2G calcium/calmodulin-dependent protein kinase (CaM kinase) II gamma". Moyers JS, Bilan PJ, Zhu J, Kahn CR ( ... calmodulin-dependent protein kinase subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic ... "Phosphorylation and inhibition of type III adenylyl cyclase by calmodulin-dependent protein kinase II in vivo". J. Biol. Chem. ...
Cannabinoids reduce calcium influx by blocking the activity of voltage-dependent N-, P/Q- and L-type calcium channels. In ... through Gi/o-mediated inhibition of adenylyl cyclase and protein kinase A. Direct effects of CB1 receptors on membrane ... decreases in expression were seen in both calmodulin and ribosomal RNAs (Kittler et al., 2000). In addition, CB1 activation has ... Guo J, Ikeda SR (2004). "Endocannabinoids modulate N-type calcium channels and G-protein-coupled inwardly rectifying potassium ...
Calcium/calmodulin-dependent protein kinase type II beta chain is an enzyme that in humans is encoded by the CAMK2B gene. The ... CAMK2B calcium/calmodulin-dependent protein kinase (CaM kinase) II beta". Walikonis RS, Oguni A, Khorosheva EM, Jeng CJ, ... Novak G, Seeman P, Tallerico T (2001). "Schizophrenia: elevated mRNA for calcium-calmodulin-dependent protein kinase IIbeta in ... calmodulin-dependent protein kinase subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic ...
Barry FA, Gibbins JM (Apr 2002). "Protein kinase B is regulated in platelets by the collagen receptor glycoprotein VI". The ... Andrews RK, Suzuki-Inoue K, Shen Y, Tulasne D, Watson SP, Berndt MC (Jun 2002). "Interaction of calmodulin with the cytoplasmic ... Collagen fibers are the most thrombogenic macromolecular components of the extracellular matrix, with collagen types I, III, ... "Expression and function of the mouse collagen receptor glycoprotein VI is strictly dependent on its association with the ...
... an effect which is associated with DAT phosphorylation through a Ca2+/calmodulin-dependent protein kinase (CAMK)-dependent ... calcium/calmodulin protein kinases) signaling, which, in addition to phosphorylating CREB, also phosphorylates HDAC5. Figure 2 ... ΔFosB is also induced in D1-type NAc MSNs by chronic consumption of several natural rewards, including sucrose, high fat food, ... it triggers transporter phosphorylation via protein kinase A (PKA) and protein kinase C (PKC) signaling, ultimately resulting ...
Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C is an enzyme that in humans is encoded by the PDE1C ... Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/ ... 2006). "Subcellular localization and regulation of type-1C and type-5 phosphodiesterases". Biochem. Biophys. Res. Commun. 341 ( ... "Entrez Gene: PDE1C phosphodiesterase 1C, calmodulin-dependent 70kDa". Vandeput F, Wolda SL, Krall J, et al. (2007). "Cyclic ...
Calcium/calmodulin-dependent protein kinase type II alpha chain (CAMKIIα) is an enzyme that in humans is encoded by the CAMK2A ... Phosphorylation by cyclic AMP-dependent protein kinase, protein kinase C, and calcium/calmodulin protein kinase; identification ... "Entrez Gene: CAMK2A calcium/calmodulin-dependent protein kinase (CaM kinase) II alpha". Walikonis RS, Oguni A, Khorosheva EM, ... calmodulin-dependent protein kinase II phosphorylates various types of non-epithelial intermediate filament proteins". Biochem ...
"Calmodulin is involved in the Ca2+-dependent activation of ceramide kinase as a calcium sensor". J. Biol. Chem. 280 (49): 40436 ... CERK shares sequence homology with sphingosine kinase type I, including an N-terminal pleckstrin homology (PH) domain and a ... It was demonstrated that C-1-P perpetuates the phosphorylation of glycogen synthase kinase-3 β and retinoblastoma protein, ... CERK was later confirmed to bind calmodulin in the presence of calcium, indicating the calmodulin first binds calcium and then ...
... the microtubule-associated tau proteins and S100b regulate tau phosphorylation by the Ca2+/calmodulin-dependent protein kinase ... "The calcium-modulated proteins, S100A1 and S100B, as potential regulators of the dynamics of type III intermediate filaments". ... S100 calcium-binding protein B (S100B) is a protein of the S-100 protein family. S100 proteins are localized in the cytoplasm ... the microtubule-associated tau proteins and S100b regulate tau phosphorylation by the Ca2+/calmodulin-dependent protein kinase ...
... a novel two EF-hand calcium-binding protein that suppresses Ca2+/calmodulin-dependent protein kinase II activity in the brain ... Expression of CaBP1 helps to block Ca2+-dependent facilitation of P/Q-type Ca2+ current which is markedly reduced facilitation ... Calcium binding protein 1 is a protein that in humans is encoded by the CABP1 gene. Calcium-binding protein 1 is a calcium- ... Calcium-binding protein 1 which is a neuron -specific member of the calmodulin (CaM) superfamily which modulates Ca2+-dependent ...
"Structure and expression of a calcium-binding protein gene contained within a calmodulin-regulated protein kinase gene". ... encodes myosin light chain kinase which is a calcium/calmodulin dependent enzyme. Four transcript variants that produce four ... Reaction type: phospho group transfer) It requires Ca2+ and calmodulin for activity. The 20-kDa light chain from smooth muscle ... "Kinase-related protein (telokin) is phosphorylated by smooth-muscle myosin light-chain kinase and modulates the kinase activity ...
... p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II and alpha-actinin-1 in a calcium-dependent ... Actinin, alpha 1 has been shown to interact with: CDK5R1, CDK5R2, Collagen, type XVII, alpha 1, GIPC1, PDLIM1, Protein kinase ... Alpha actinin is an actin-binding protein with multiple roles in different cell types. In nonmuscle cells, the cytoskeletal ... Bunn RC, Jensen MA, Reed BC (1999). "Protein interactions with the glucose transporter binding protein GLUT1CBP that provide a ...
Calcium channel, voltage-dependent, L type, alpha 1C subunit (also known as Cav1.2) is a protein that in humans is encoded by ... When depolarization occurs, calcium ions flow through the channel and some bind to Calmodulin. The Calcium/Calmodulin binding ... Perets T, Blumenstein Y, Shistik E, Lotan I, Dascal N (Apr 1996). "A potential site of functional modulation by protein kinase ... This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx of calcium ...
Calcium-Calmodulin-Dependent Protein Kinase Type 2 Calcium-Calmodulin-Dependent Protein Kinases ... Mutational analysis of Ca2+-independent autophosphorylation of calcium/calmodulin-dependent protein kinase II. In: Journal of ... Mutational analysis of Ca2+-independent autophosphorylation of calcium/calmodulin-dependent protein kinase II. / Mukherji, ... title = "Mutational analysis of Ca2+-independent autophosphorylation of calcium/calmodulin-dependent protein kinase II", ...
Calcium Amino Acids Bearings (structural) Calcium-Calmodulin-Dependent Protein Kinase Type 2 ... T2 - Conformational changes induced by calmodulin-binding peptides from myosin light chain kinase and protein kinase II ... or calmodulin-dependent protein kinase II (CaMPK-II), respectively. Both steady-state and time-resolved fluorescence data were ... or calmodulin-dependent protein kinase II (CaMPK-II), respectively. Both steady-state and time-resolved fluorescence data were ...
Member of the NMDAR signaling complex in excitatory synapses it may regulate NMDAR-dependent potentiation of the AMPAR and ... is a prominent kinase in the central nervous system that may function in long-term potentiation and neurotransmitter release. ... Calcium/calmodulin-dependent protein kinase type II subunit alpha (EC:2.7.11.17By similarity. ,p>Manually curated information ... View protein in PROSITE. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 ...
Protein KinasesProtein-Serine-Threonine KinasesCalcium-Calmodulin-Dependent Protein KinasesCalcium-Calmodulin-Dependent Protein ... Signaling Peptides and ProteinsCalcium-Calmodulin-Dependent Protein KinasesCalcium-Calmodulin-Dependent Protein Kinase Type 2 ... Signaling Peptides and ProteinsCalcium-Calmodulin-Dependent Protein KinasesCalcium-Calmodulin-Dependent Protein Kinase Type 2 ... Calmodulin-Dependent Protein Kinase II. *Calmodulin Dependent Protein Kinase II. *Calcium-Calmodulin-Dependent Protein Kinase ...
... Daniels, Lorna Jane ... Cite this item: Daniels, L. J. (2017). The role of calcium calmodulin dependent protein kinase II in type 2 diabetic heart ... has shown that diabetic patients and mouse models of diabetes have an up-regulation of calmodulin-dependent protein kinase ... Type 2 diabetes is a well-established risk factor for cardiovascular disease, with the landmark Framingham study in the 1970s ...
calcium/calmodulin-dependent protein kinase type II subunit alpha isoform 2 [Homo sapiens]. NCBI Reference Sequence: NP_ ... calcium/calmodulin-dependent protein kinase type II subunit alpha isoform 2 [Hom... calcium/calmodulin-dependent protein kinase ... The product of this gene belongs to the serine/threonine protein kinases family, and to the Ca(2+)/calmodulin-dependent protein ... Transcript/Protein Information [PANTHER Classification System] Transcript/Protein Information. PANTHER Classification System ...
... and BDNF-dependent mechanisms and their crosstalk in the hippocampus, including potential implications for the pathogenesis of ... dependent mechanisms and their crosstalk in the hippocampus, including potential implications for the pathogenesis of common ... tropomyosin-related kinase receptor B (TrkB). This review addresses the effects of ELS paradigms on GC- and BDNF- ... tropomyosin-related kinase receptor B (TrkB). This review addresses the effects of ELS paradigms on GC- ...
Calcium/calmodulin-dependent protein kinase kinase 2: roles in signaling and pathophysiology. J Biol Chem. 2012;287(38):31658- ... Macroscopic raw traces of L-type calcium current comparing IV-3 against CRISPR-corrected IV-3. (H) Summary L-type calcium ... Regulation of voltage-dependent calcium channels by RGK proteins. Biochim Biophys Acta. 2013;1828(7):1644-1654.. View this ... L-type calcium current density increase revealed by patient-specific iPSC-CMs. (A) Representative macroscopic whole-cell L-type ...
... the mechanisms that underlie experience-dependent transcriptional regulation of the rate-limiting serotonin biosynthetic enzyme ... Caenorhabditis elegans Proteins / genetics*, metabolism. Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics*, ... EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinase Type 2; EC 2.7.11.17/unc-43 protein, C elegans; EC 3.6.5.1/GTP-Binding ... Upstream of ADF, the Gqα protein EGL-30 facilitates training-dependent induction of tph-1 by functional regulation of olfactory ...
The role of calcium calmodulin dependent protein kinase II in type 2 diabetic cardiac dysfunction. Verbal presentation at the ... The role of calcium calmodulin dependent protein kinase II in type 2 diabetic cardiac dysfunction. Verbal presentation at the ... of calcium/calmodulin-dependent kinase II restores contraction and relaxation in isolated cardiac muscle from type 2 diabetic ... of calcium/calmodulin-dependent kinase II restores contraction and relaxation in isolated cardiac muscle from type 2 diabetic ...
The role of calcium calmodulin dependent protein kinase II in type 2 diabetic cardiac dysfunction. Verbal presentation at the ... effect of calcium/calmodulin-dependent kinase II on Cav1.2 Protein. Heart, Lung & Circulation, 26(Suppl. 2), (pp. S109). doi: ... of calcium/calmodulin-dependent protein kinase II δ. Journal of Biological Chemistry, 290(42), 25646-25656. doi: 10.1074/jbc. ... of calcium/calmodulin-dependent kinase II restores contraction and relaxation in isolated cardiac muscle from type 2 diabetic ...
This indicates the type of evidence that supports the existence of the protein. Note that the protein existence evidence does ... View protein in PROSITE. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 ... View protein in PROSITE. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 ... Calcium/calmodulin-dependent protein kinase (CaM kinase) II alpha, isoform CRA_aImported. ,p>Information which has been ...
CalciumIBA 06/2015. 1. Calcium-Calmodulin-Dependent Protein Kinase Type 2IBA 06/2015. ... Involvement of hypothalamic AMP-activated protein kinase in leptin-induced sympathetic nerve activation.. ... the hypothalamus regulates hepatic autonomic nerve activity via phosphatidylinositol 3-kinase and AMP-activated protein kinase. ... Neuronal receptor activity-modifying protein 1 promotes energy expenditure in mice.. For more, sign up at right for free... ...
L-type calcium channel; MCU, mitochondria calcium uniporter; NCX, Na+/Ca2+ exchanger; NHE, Na+/H+ exchanger; PKA, protein ... Calcium-calmodulin dependent protein kinase II (CaMKII): a main signal responsible for early reperfusion arrhythmias. J Mol ... In Vivo Post-Cardiac Arrest Myocardial Dysfunction Is Supported by Ca2+/Calmodulin-Dependent Protein Kinase II-Mediated Calcium ... E, Proposed mechanism for PMAD, mediated by calcium overload, Ca2+/calmodulin-dependent protein kinase II (CaMKII), and ...
Calcium/metabolism*. *Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism*. *Calmodulin/metabolism* ... Dendrite formation involves activation of Ca2+/Calmodulin (CaM)-dependent kinase II (CaMKII) by CaM. Previous work showed that ... Dendrite formation involves activation of Ca2+/Calmodulin (CaM)-dependent kinase II (CaMKII) by CaM. Previous work showed that ... Mentions: Stimulation of MEL receptors (MT1/2) causes PKC activation that has been shown to be involved in physiological ...
CAMK4 is calcium/calmodulin-dependent protein kinase, that via phosphorylation, triggers the CaMKK-CaMK4 signaling cascade and ... MEF2 responds to multiple calcium-regulated signals in the control of skeletal muscle fiber type. Embo j 19, 1963-1973, https ... Profiling of human lymphocytes reveals a specific network of protein kinases modulated by endurance training status *Katharina ... Corepressor-dependent silencing of chromosomal regions encoding neuronal genes. Science (New York, N.Y.) 298, 1747-1752, https ...
Calcium-Calmodulin-Dependent Protein Kinase Type 2/antagonists & inhibitors/metabolism. *Disease Models, Animal ... Calcium-Calmodulin-Dependent Protein Kinase Type 2/antagonists & inhibitors/metabolism. *Disease Models, Animal ...
... temporal and region-specific requirements of the beta isoform of Calcium/Calmodulin-dependent protein kinase type 2 (CAMK2B) in ... temporal and region-specific requirements of the beta isoform of Calcium/Calmodulin-dependent protein kinase type 2 (CAMK2B) in ... Kinase activity is not required for αCaMKII-dependent presynaptic plasticity at CA3-CA1 synapses *Mohammad Reza Hojjati ... Rights & permissionsfor article Kinase activity is not required for αCaMKII-dependent presynaptic plasticity at CA3-CA1 ...
... and CaMKII alpha and beta protein levels. In the hippocampus of Pb2+-exposed 50-day-old rats known to exhib ... we examined whether calcium/calmodulin-dependent protein kinase II (CaMKII) is affected by chronic developmental Pb2+ exposure ... Calcium/calmodulin dependent protein kinase II (CaMKII); NMDA receptor (NMDAR); Lead (Pb2+); Calcium signaling; Enzyme kinetics ... Calcium/calmodulin-dependent protein kinase II activity and expression are altered in the hippocampus of Pb2+- exposed rats.. ...
While activation of calcium-calmodulin (CaM)-dependent protein kinase II (CaMKII) is a key event in calcium signaling, its role ... Aberrant calcium signaling is a common feature of ischemia and multiple neurodegenerative diseases. ... Calcium-Calmodulin-Dependent Protein Kinase Type 2 / antagonists & inhibitors *. Actions. * Search in PubMed ... While activation of calcium-calmodulin (CaM)-dependent protein kinase II (CaMKII) is a key event in calcium signaling, its role ...
Effect of NMDA on the M3-muscarinic receptor phosphoinositide response is dependent on calcium entry and CamKII activity. CG ... Calcium Signaling. *Calcium-Calmodulin-Dependent Protein Kinase Type 2/antagonists & inhibitors/genetics/metabolism ... through a mechanism dependent on NMDA-mediated calcium influx and the activity of calcium-calmodulin-dependent protein kinase ... through a mechanism dependent on NMDA-mediated calcium influx and the activity of calcium-calmodulin-dependent protein kinase ...
Calcium-Calmodulin-Dependent Protein Kinase Type 2/deficiency/genetics/metabolism*. *Cardiomegaly/enzymology*/genetics/ ... Calcium-Calmodulin-Dependent Protein Kinase Type 2/deficiency/genetics/metabolism*. *Cardiomegaly/enzymology*/genetics/ ... 14-3-3 binding increased significantly at the ANP and β-MHC promoters and exonic region after stress in wild-type mice, but ... 14-3-3 binding increased significantly at the ANP and β-MHC promoters and exonic region after stress in wild-type mice, but ...
Calcium-Calmodulin-Dependent Protein Kinase Type 2 Phosphorylation Retroelements Hippocampus Learning Estrogen-Dependent ...
Calcium-Calmodulin-Dependent Protein Kinase Type 2 * Actins * Actin Cytoskeleton * Synapses * Monomers ... Type Language Publication Year Top Authors Concepts Research Units Collaborators Open Access ... β-sheet proteins with nearly identical structures have different folding intermediates. Dalessio, P. M. & Ropson, I. J., Feb 8 ... γ-aminobutyric acid type A (GABA A) receptor α subunits play a direct role in synaptic Versus extrasynaptic targeting. Wu, X., ...
Calcium-Calmodulin-Dependent Protein Kinase Type 2 View all 19 research output ... Mice lacking GRIP1/2 show increased social interactions and enhanced phosphorylation at GluA2-S880. Han, M., Mejias, R., Chiu, ... Neuropilin-2/PlexinA3 Receptors Associate with GluA1 and Mediate Sema3F-Dependent Homeostatic Scaling in Cortical Neurons. Wang ... Purkinje cell-specific Grip1/2 knockout mice show increased repetitive self-grooming and enhanced mGluR5 signaling in ...
  • None of the mutants exhibited enhanced Ca 2+ -independent kinase activity toward exogenous substrate, but the K300S and N294S mutants showed a significant enhancement in the rate and stoichiometry of 32 P incorporation during Ca 2+ -independent autophosphorylation. (elsevier.com)
  • This specific Ca 2+ -independent autophosphorylation of Ser 300 is consistent with the hypothesis that Arg 297 may occupy the P (-3) position in a pseudosubstrate autoinhibitory interaction with the catalytic core in the nonactivated state of the kinase. (elsevier.com)
  • Peptide-induced conformational changes in five isofunctional mutants of calmodulin (CaM), each bearing a single tryptophan residue either at the seventh position of each of the four calcium-binding loops (i.e., amino acids 26, 62, 99, and 135) or in the central helix (amino acid 81) were studied by using fluorescence spectroscopy. (elsevier.com)
  • Steady-state fluorescence intensity measurements indicated that, in the presence of an excess of calcium, both peptides bind to the calmodulin mutants with a 1:1 stoichiometry. (elsevier.com)
  • Both peptides induced similar changes in the fluorescence properties of the tryptophan residues located in the calcium-binding loops, with the exception of calmodulin with Trp-135. (elsevier.com)
  • Upstream of ADF, the Gqα protein EGL-30 facilitates training-dependent induction of tph-1 by functional regulation of olfactory sensory neurons, which underscores the importance of sensory experience. (biomedsearch.com)
  • In primary cortical neurons, BDNF elicited phosphorylation of AKT and p70S6 kinase is attenuated in the presence of myelin inhibitors. (jneurosci.org)
  • The altered neuronal activity caused by these two drugs is accompanied by changes in intracellular calcium concentrations and Ca 2+ /calmodulin-dependent protein (CaM) kinase II activity in dopamine neurons. (elsevier.com)
  • G-protein-coupled inwardly rectifying potassium (GIRK) channels contribute to the resting membrane potential of many neurons, including dopamine (DA) neurons in the ventral tegmental area (VTA). (nih.gov)
  • In conclusion, activity-dependent GIRK channel plasticity may represent a slow destabilization process favoring the switch between the two firing modes of VTA DA neurons. (nih.gov)
  • However, programming schemes produce a variety of cell types, and those neurons that are made often retain an immature phenotype, which limits their utility in modeling neuronal processes, including synaptic transmission. (nih.gov)
  • Vascular endothelial growth factor (VEGF) signaling regulates hippocampal neurons by elevation of intracellular calcium and activation of calcium/c. (nih.gov)
  • The present study was undertaken to characterize neuronal activity-dependent expression and release of vascular endothelial growth factor (VEGF) from rat hippocampal neurons and its contribution to neuronal functions. (nih.gov)
  • A brief (10 min) application of recombinant VEGF165 to neurons elicited a slow rise in cytosolic Ca2+ in a VEGFR2 dependent manner. (nih.gov)
  • Indeed, experience-dependent changes in the strength of synaptic connections between neurons are thought to underlie information storage in the brain. (aston.ac.uk)
  • However, CRMP-2 and CRMP-5 are found to be co-expressed in post-mitotic granular neurons. (wikipedia.org)
  • Among the five members of the CRMP family, CRMP-2 is the most highly expressed in the adult brain, especially in post-mitotic neurons of the olfactory system, cerebellum, and hippocampus. (wikipedia.org)
  • Lack of synapsins altogether in neurons, leads to behavioral alterations as well as epileptic-type seizures. (wikipedia.org)
  • This enzyme is a multifunctional serine/threonine protein kinase with limited tissue distribution, that has been implicated in transcriptional regulation in lymphocytes, neurons and male germ cells. (wikipedia.org)
  • The neurons, neural pathways, and other cells where these molecules, enzymes, and one or both cannabinoid receptor types are all colocalized collectively comprise the endocannabinoid system. (wikipedia.org)
  • Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (e.g., muscle, glial cells, neurons, etc.) with a permeability to the calcium ion Ca2+. (wikipedia.org)
  • Activation of particular VGCCs allows Ca2+ to rush into the cell, which, depending on the cell type, results in activation of calcium-sensitive potassium channels, muscular contraction, excitation of neurons, up-regulation of gene expression, or release of hormones or neurotransmitters. (wikipedia.org)
  • Isoform Inositol Trisphosphate 3 Kinase A is predominant in neurons and in the testes. (wikipedia.org)
  • Preliminary evidence suggests that the dopamine transporter couples to L-type voltage-gated calcium channels (particularly Cav1.2 and Cav1.3), which are expressed in virtually all dopamine neurons. (wikipedia.org)
  • As a result of DAT-Cav coupling, DAT substrates that produce depolarizing currents through the transporter are able to open calcium channels that are coupled to the transporter, resulting in a calcium influx in dopamine neurons. (wikipedia.org)
  • Previous research indicated that the active zone of glutamatergic neurons contained a highly regular array of pyramid shaped protein dense material and indicated that these pyramids were connected by filaments. (wikipedia.org)
  • The increased levels of nerve growth factor and tumour necrosis factor-α (TNF-α) causes the upregulation of Nav1.8 in sensory neurons via the accessory protein p11 (annexin II light chain). (wikipedia.org)
  • In excitable cells such as neurons, myocytes, and certain types of glia, sodium channels are responsible for the rising phase of action potentials. (wikipedia.org)
  • Work from the lab has characterized many of the fundamental steps in this process, from the initial activation of ion channels that depolarize neurons, the subsequent downstream signaling cascade that culminates in gene expression, and the pattern of experience-dependent gene expression in particular subtypes of cells in the brain, such as inhibitory versus excitatory neurons. (wikipedia.org)
  • The Greenberg lab is also studying activity-dependent gene expression in human neurons, and is comparing this program of gene expression to other mammals and other primates. (wikipedia.org)
  • Odorants penetrate into the cuticle pores of chemosensory sensilla and get in contact with insect odorant-binding proteins (OBPs) or Chemosensory proteins (CSPs), before activating the sensory neurons. (wikipedia.org)
  • ΔFosB expression in D1-type nucleus accumbens medium spiny neurons directly and positively regulates drug self-administration and reward sensitization through positive reinforcement while decreasing sensitivity to aversion. (wikipedia.org)
  • ΔFosB is the most significant biomolecular mechanism in addiction because the overexpression of ΔFosB in the D1-type medium spiny neurons in the nucleus accumbens is necessary and sufficient for many of the neural adaptations and behavioral effects (e.g., expression-dependent increases in drug self-administration and reward sensitization) seen in drug addiction. (wikipedia.org)
  • Half of the synapsing axons and dendritic spines are physically tethered by calcium-dependent cadherin, which forms cell-to-cell adherent junctions between two neurons. (wikipedia.org)
  • Glutamatergic neurons make and release in an activity-dependent manner the excitatory neurotransmitter glutamate as opposed to the inhibitory neurotransmitter GABA. (wikipedia.org)
  • In cultured hippocampal neurons, Tbr1 and calcium/calmodulin-dependent serine kinase (CASK) interact with CASK-interacting nucleosome assembly protein (CINAP) to modulate the expression of N-methyl-D-aspartic acid receptor subunit 2b (NR2b) by acting on its promoter region. (wikipedia.org)
  • The two amphetamine enantiomers that compose Adderall (i.e., levoamphetamine and dextroamphetamine) alleviate the symptoms of ADHD and narcolepsy by increasing the activity of the neurotransmitters norepinephrine and dopamine in the brain, which results in part from their interactions with trace amine associated receptor 1 (TAAR1) and vesicular monoamine transporter 2 (VMAT2) in neurons. (wikipedia.org)
  • This suggests that NgR1 and PirB participate in ligand-dependent inhibition of synaptic plasticity. (jneurosci.org)
  • CaM-kinases: modulators of synaptic plasticity. (nih.gov)
  • Sustained activation of CaM-KII localized at the postsynaptic density results in phosphorylation of numerous synaptic substrates including ion channels, other signaling molecules and scaffolding proteins, to modulate synaptic transmission within minutes. (nih.gov)
  • The same brief stimulus with VEGF led to long-term synaptic enhancement dependent on protein synthesis. (nih.gov)
  • A model for regulation by SynGAP-α1 of binding of synaptic proteins to PDZ-domain 'Slots' in the postsynaptic density. (nih.gov)
  • Competition among synaptic proteins for binding to PDZ domains of PSD-95. (nih.gov)
  • Synapsin II along with synapsin I comprise approximately 9% of the proteins in highly purified samples of synaptic vesicles. (wikipedia.org)
  • This protein is a multidomain scaffolding protein with a role in synaptic transmembrane protein anchoring and ion channel trafficking. (wikipedia.org)
  • Expression of CaBP1 helps to block Ca2+-dependent facilitation of P/Q-type Ca2+ current which is markedly reduced facilitation of synaptic transmission. (wikipedia.org)
  • CABP1 also interacts with CACNA1A in the pre and post synaptic membranes via C-terminal calcium binding motif. (wikipedia.org)
  • This interaction occurs in calcium dependent manner after the Synaptic NMDA receptor stimulation and thus this prevents nuclear import of NSMF. (wikipedia.org)
  • Of note, AMPARs cannot directly bind to the common synaptic protein PSD-95 owing to incompatible PDZ domains, although they do interact with PSD-95 via stargazin (the prototypical member of the TARP family of AMPAR auxiliary subunits). (wikipedia.org)
  • The currently exposed interactions of Densin-180 portray the protein as a promiscuous player amongst key synaptic players, fitting with the original observation of the protein's dense presence among core PSD proteins by Mary B. Kennedy's Laboratory. (wikipedia.org)
  • The compelling properties of calcium calmodulin kinase II, one of the topics discussed in that symposium, and an elegant model by John Lisman proposing a key role for that kinase in hippocampal learning and memory, persuaded Silva to refocus his project in the Tonegawa laboratory on the role of the alpha calcium calmodulin kinase II in hippocampal synaptic plasticity and learning & memory. (wikipedia.org)
  • This early work with hippocampal mutations that affected long term potentiation and learning & memory became the basis for a large literature that now has definitively implicated stable changes in synaptic plasticity in the hippocampal CA1 region in hippocampal dependent learning and memory. (wikipedia.org)
  • The dopamine transporter (also dopamine active transporter, DAT, SLC6A3) is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synaptic cleft back into cytosol. (wikipedia.org)
  • DAT is an integral membrane protein that removes dopamine from the synaptic cleft and deposits it into surrounding cells, thus terminating the signal of the neurotransmitter. (wikipedia.org)
  • The synaptotagmins are integral membrane proteins of synaptic vesicles thought to serve as Ca(2+) sensors in the process of vesicular trafficking and exocytosis. (wikipedia.org)
  • Confocal and two-photon microscopes provide improved sectioning ability so that calcium signals can be resolved in micro domains or (for example) synaptic boutons. (wikipedia.org)
  • Proteins within the CAZ tether synaptic vesicles to the presynaptic membrane and mediate synaptic vesicle fusion, thereby allowing neurotransmitter to be released reliably and rapidly when an action potential arrives. (wikipedia.org)
  • The active zones examined so far have at least two features in common, they all have protein dense material that project from the membrane and tethers synaptic vesicles close to the membrane and they have long filamentous projections originating at the membrane and terminating at vesicles slightly farther from the presynaptic membrane. (wikipedia.org)
  • One striking example of the dense projection is the ribbon synapse (see below) which contains a "ribbon" of protein dense material that is surrounded by a halo of synaptic vesicles and extends perpendicular to the presynaptic membrane and can be as long as 500 nm. (wikipedia.org)
  • These scaffold proteins are thought to be the constituents of the dense pyramid like structures of the active zone and are thought to bring the synaptic vesicles into close proximity to the presynaptic membrane and the calcium channels. (wikipedia.org)
  • The term "plasticity product" was coined by Jerry Rudy to refer to mRNA genetic artifacts and protein products triggered by transcription factors, leading long-lasting long term potentiation (L-LTP) and sustained alterations in synaptic strength. (wikipedia.org)
  • mRNA is produced leading to subsequent translation of new proteins to sustain synaptic changes. (wikipedia.org)
  • cAMP-responsive element-binding (CREB) protein, a transcription factor, is also implicated in changes in synaptic plasticity. (wikipedia.org)
  • Local protein synthesis at the dendrites is a mechanism permitting rapid synaptic changes in response to neural activity. (wikipedia.org)
  • Dextroamphetamine, like other amphetamines, elicits its stimulating effects via several distinct actions: it inhibits or reverses the transporter proteins for the monoamine neurotransmitters (namely the serotonin, norepinephrine and dopamine transporters) either via trace amine-associated receptor 1 (TAAR1) or in a TAAR1 independent fashion when there are high cytosolic concentrations of the monoamine neurotransmitters and it releases these neurotransmitters from synaptic vesicles via vesicular monoamine transporter 2. (wikipedia.org)
  • This review evaluates recent advances in mechanisms underlying aldosterone-induced cardiac disease and highlights the interplay between aldosterone and Ca 2+ /calmodulin dependent protein kinase II, whose hyperactivity during heart failure contributes to disease progression. (elsevier.com)
  • activated potassium channel subtype 2(SK2) in mouse cardiac myocytes. (nih.gov)
  • Skeletal Muscle is one of three major muscle types, the others being cardiac muscle and smooth muscle. (wikipedia.org)
  • Alpha-actinin 2 also functions in docking signalling molecules at Z-discs, and additional studies have also implicated alpha-actinin 2 in the binding of cardiac ion channels, Kv1.5 in particular. (wikipedia.org)
  • Cardiac Organellar Protein Atlas Knowledgebase. (wikipedia.org)
  • Both GsPCR and GqPCR activation can contribute to cardiac hypertrophy via activation of MAP Kinases as well. (wikipedia.org)
  • An alternatively spliced form of nNOS is a major muscle protein that produces signals in response to calcium release from the SR. nNOS in the heart protects against cardiac arrhythmia induced by myocardial infarction. (wikipedia.org)
  • S100A1 is a member of the S100 family of proteins expressed in cardiac muscle, skeletal muscle and brain, with highest density at Z-lines and sarcoplasmic reticulum. (wikipedia.org)
  • The pathophysiology of heart failure is often a consequence of improper calcium handling and relaxation resulting in a lower cardiac output, decreased blood flow and overall decreased heart function. (wikipedia.org)
  • Infusion of Ucn2 in healthy humans has shown a dose dependent increase in cardiac output, heart rate and left ventricle ejection fraction and a decrease in systemic vascular resistance. (wikipedia.org)
  • Plasticity Product is a term coined by Jerry Rudy to refer to mRNA genetic artifacts and protein products triggered by transcription factors leading to long-lasting long term potentiation. (wikipedia.org)
  • Rudy differentiates between two types of long term potentiation: S-LTP (short-lasting) and L-LTP (long-lasting). (wikipedia.org)
  • The modulation of CRMP-2 expression through various pharmaceuticals is a new and expanding area of research. (wikipedia.org)
  • Family members are characterized by common protein domains, and they are implicated in synaptogenesis and the modulation of neurotransmitter release, suggesting a potential role in several neuropsychiatric diseases. (wikipedia.org)
  • While it is primarily a ligand-gated channel, it does display weaker voltage-dependence modulation of the ligand-dependent gating. (wikipedia.org)
  • Alternatively, variants of GFP are fused with the calcium binding protein troponin C (TnC), applying the mechanism of FRET (Förster Resonance Energy Transfer) for signal modulation. (wikipedia.org)
  • synGAP is a neuron-specific Ras and Rap GTPase-activating protein (GAP) found in high concentrations in the postsynaptic density (PSD) fraction from the mammalian forebrain. (nih.gov)
  • Found to be densely associated to the postsynaptic density (PSD), it has been characterised as a 188 kDa (originally thought to be 180 kDa, hence nomenclature), 1495 residues long, brain-specific protein containing 16 leucine-rich repeats (LRRs) within the 500 N-terminal residues, and one Psd95/Discs large/Zona occludens (PDZ) domain within the 200 C-terminal residues. (wikipedia.org)
  • Signalling from GluRs is mediated by the presence of an abundance of proteins, especially kinases, that are localized to the postsynaptic density. (wikipedia.org)
  • View conserved domains detected in this protein sequence using CD-search. (nih.gov)
  • Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed. (uniprot.org)
  • The cDNA sequence of TOAD-64 corresponded to that of rat CRMP-2. (wikipedia.org)
  • In the same year, several other studies cloned CRMPs-1-4 in rat and dihydropyrimidinase (DHPase) homologous sequence of CRMPs-1, -2, and -4 in human fetal brain. (wikipedia.org)
  • The protein sequence of CRMP1-4 is approximately 75% homologous with each other, while CRMP5 is only 50-51% homologous with each of the other CRMPs. (wikipedia.org)
  • The proteins destined to be secreted or sorted to other cell organelles carry an N-terminal signal sequence that will interact with a signal recognition particle (SRP). (wikipedia.org)
  • Once the sequence has "docked", the protein continues translation, with the resultant strand being fed through the polypeptide translocator directly into the ER. (wikipedia.org)
  • CERK shares sequence homology with sphingosine kinase type I, including an N-terminal pleckstrin homology (PH) domain and a diacylglycerol kinase domain. (wikipedia.org)
  • The reductase domain is linked to the oxidase domain by a calmodulin-binding sequence. (wikipedia.org)
  • Protein sequence alignment shows that calponin 1 is highly conserved in mammals but more diverged among lower vertebrates. (wikipedia.org)
  • numbering refers to the mouse sequence) are localized in the M motif of cMyBP-C and are targeted by protein kinases in a hierarchical order of events. (wikipedia.org)
  • The specific DNA sequence for the rod domain may differ between different type III intermediate filaments, but the structure of the protein is highly conserved. (wikipedia.org)
  • A protein domain is a conserved part of a given protein sequence and (tertiary) structure that can evolve, function, and exist independently of the rest of the protein chain. (wikipedia.org)
  • Helix 3, 4, and the hinge region are the most divergent areas between individual S100 proteins, and so it is likely that the sequence of these regions is pivotal in fine-tuning calcium-dependent target binding by S100 proteins. (wikipedia.org)
  • A Cyclic nucleotide-binding domain is an intracellular domain located in the C-terminus region and has a similar sequence to other cyclic nucleotide-binding proteins. (wikipedia.org)
  • This protein shares regions of very high-sequence similarity with protein EP300 in its bromodomain, cysteine-histidine-rich regions, and histone acetyltransferase domain. (wikipedia.org)