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.Trifluoperazine: A phenothiazine with actions similar to CHLORPROMAZINE. It is used as an antipsychotic and an antiemetic.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.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.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.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.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.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.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.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.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.Sulfonamides: A group of compounds that contain the structure SO2NH2.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Kinetics: The rate dynamics in chemical or physical systems.Egtazic Acid: A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.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)2',3'-Cyclic-Nucleotide Phosphodiesterases: Nucleoside-2',3'-cyclic phosphate nucleotidohydrolase. Enzymes that catalyze the hydrolysis of the 2'- or 3'- phosphate bonds of 2',3'-cyclic nucleotides. Also hydrolyzes nucleoside monophosphates. Includes EC 3.1.4.16 and EC 3.1.4.37. EC 3.1.4.-.Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking DOPAMINE RECEPTORS. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup.Calcium-Transporting ATPases: Cation-transporting proteins that utilize the energy of ATP hydrolysis for the transport of CALCIUM. They differ from CALCIUM CHANNELS which allow calcium to pass through a membrane without the use of energy.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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.3',5'-Cyclic-AMP Phosphodiesterases: Enzymes that catalyze the hydrolysis of CYCLIC AMP to form adenosine 5'-phosphate. The enzymes are widely distributed in animal tissue and control the level of intracellular cyclic AMP. Many specific enzymes classified under this heading demonstrate additional spcificity for 3',5'-cyclic IMP and CYCLIC GMP.Neurogranin: A BRAIN-specific substrate for PROTEIN KINASE C that binds CALMODULIN and is involved in regulation of CALCIUM SIGNALING.Sesterterpenes: Terpenes of five units of HEMITERPENES, formed from geranylfarnesyl pyrophosphate.Melitten: Basic polypeptide from the venom of the honey bee (Apis mellifera). It contains 26 amino acids, has cytolytic properties, causes contracture of muscle, releases histamine, and disrupts surface tension, probably due to lysis of cell and mitochondrial membranes.Cyclic Nucleotide Phosphodiesterases, Type 1: A CALCIUM and CALMODULIN-dependent cyclic nucleotide phosphodiesterase subfamily. The three members of this family are referred to as type 1A, type 1B, and type 1C and are each product of a distinct gene. In addition, multiple enzyme variants of each subtype can be produced due to multiple alternative mRNA splicing. Although the type 1 enzymes are classified as 3',5'-cyclic-AMP phosphodiesterases (EC 3.1.4.17), some members of this class have additional specificity for CYCLIC GMP.Calcineurin: A CALCIUM and CALMODULIN-dependent serine/threonine protein phosphatase that is composed of the calcineurin A catalytic subunit and the calcineurin B regulatory subunit. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including HISTONES; MYOSIN LIGHT CHAIN; and the regulatory subunits of CAMP-DEPENDENT PROTEIN KINASES. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes.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.Phenothiazines: Compounds containing dibenzo-1,4-thiazine. Some of them are neuroactive.Ca(2+) Mg(2+)-ATPaseParamecium: A genus of ciliate protozoa that is often large enough to be seen by the naked eye. Paramecia are commonly used in genetic, cytological, and other research.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.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.EF Hand Motifs: Calcium-binding motifs composed of two helices (E and F) joined by a loop. Calcium is bound by the loop region. These motifs are found in many proteins that are regulated by calcium.Prenylamine: A drug formerly used in the treatment of angina pectoris but superseded by less hazardous drugs. Prenylamine depletes myocardial catecholamine stores and has some calcium channel blocking activity. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1406)Wasp Venoms: Venoms produced by the wasp (Vespid) family of stinging insects, including hornets; the venoms contain enzymes, biogenic amines, histamine releasing factors, kinins, toxic polypeptides, etc., and are similar to bee venoms.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.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.Phosphorylase Kinase: An enzyme that catalyzes the conversion of ATP and PHOSPHORYLASE B to ADP and PHOSPHORYLASE A.Chickens: Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA.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.Phosphoric Diester Hydrolases: A class of enzymes that catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound. EC 3.1.4.GizzardTroponin: One of the minor protein components of skeletal muscle. Its function is to serve as the calcium-binding component in the troponin-tropomyosin B-actin-myosin complex by conferring calcium sensitivity to the cross-linked actin and myosin filaments.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Chromatography, Affinity: A chromatographic technique that utilizes the ability of biological molecules to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Spectrometry, Fluorescence: Measurement of the intensity and quality of fluorescence.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.Fluphenazine: A phenothiazine used in the treatment of PSYCHOSES. Its properties and uses are generally similar to those of CHLORPROMAZINE.Molecular Weight: The sum of the weight of all the atoms in a molecule.Troponin C: One of the three polypeptide chains that make up the TROPONIN complex of skeletal muscle. It is a calcium-binding protein.Myosins: A diverse superfamily of proteins that function as translocating proteins. They share the common characteristics of being able to bind ACTINS and hydrolyze MgATP. Myosins generally consist of heavy chains which are involved in locomotion, and light chains which are involved in regulation. Within the structure of myosin heavy chain are three domains: the head, the neck and the tail. The head region of the heavy chain contains the actin binding domain and MgATPase domain which provides energy for locomotion. The neck region is involved in binding the light-chains. The tail region provides the anchoring point that maintains the position of the heavy chain. The superfamily of myosins is organized into structural classes based upon the type and arrangement of the subunits they contain.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Myosin Type I: A subclass of myosins found generally associated with actin-rich membrane structures such as filopodia. Members of the myosin type I family are ubiquitously expressed in eukaryotes. The heavy chains of myosin type I lack coiled-coil forming sequences in their tails and therefore do not dimerize.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)Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.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.Bee Venoms: Venoms obtained from Apis mellifera (honey bee) and related species. They contain various enzymes, polypeptide toxins, and other substances, some of which are allergenic or immunogenic or both. These venoms were formerly used in rheumatism to stimulate the pituitary-adrenal system.Erythrocyte Membrane: The semi-permeable outer structure of a red blood cell. It is known as a red cell 'ghost' after HEMOLYSIS.Actins: Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.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.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.

AMP-activated protein kinase phosphorylation of endothelial NO synthase. (1/4572)

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

Calmodulin mediates calcium-dependent activation of the intermediate conductance KCa channel, IKCa1. (2/4572)

Small and intermediate conductance Ca2+-activated K+ channels play a crucial role in hyperpolarizing the membrane potential of excitable and nonexcitable cells. These channels are exquisitely sensitive to cytoplasmic Ca2+, yet their protein-coding regions do not contain consensus Ca2+-binding motifs. We investigated the involvement of an accessory protein in the Ca2+-dependent gating of hIKCa1, a human intermediate conductance channel expressed in peripheral tissues. Cal- modulin was found to interact strongly with the cytoplasmic carboxyl (C)-tail of hIKCa1 in a yeast two-hybrid system. Deletion analyses defined a requirement for the first 62 amino acids of the C-tail, and the binding of calmodulin to this region did not require Ca2+. The C-tail of hSKCa3, a human neuronal small conductance channel, also bound calmodulin, whereas that of a voltage-gated K+ channel, mKv1.3, did not. Calmodulin co-precipitated with the channel in cell lines transfected with hIKCa1, but not with mKv1. 3-transfected lines. A mutant calmodulin, defective in Ca2+ sensing but retaining binding to the channel, dramatically reduced current amplitudes when co-expressed with hIKCa1 in mammalian cells. Co-expression with varying amounts of wild-type and mutant calmodulin resulted in a dominant-negative suppression of current, consistent with four calmodulin molecules being associated with the channel. Taken together, our results suggest that Ca2+-calmodulin-induced conformational changes in all four subunits are necessary for the channel to open.  (+info)

Interaction of NE-dlg/SAP102, a neuronal and endocrine tissue-specific membrane-associated guanylate kinase protein, with calmodulin and PSD-95/SAP90. A possible regulatory role in molecular clustering at synaptic sites. (3/4572)

NE-dlg/SAP102, a neuronal and endocrine tissue-specific membrane-associated guanylate kinase family protein, is known to bind to C-terminal ends of N-methyl-D-aspartate receptor 2B (NR2B) through its PDZ (PSD-95/Dlg/ZO-1) domains. NE-dlg/SAP102 and NR2B colocalize at synaptic sites in cultured rat hippocampal neurons, and their expressions increase in parallel with the onset of synaptogenesis. We have identified that NE-dlg/SAP102 interacts with calmodulin in a Ca2+-dependent manner. The binding site for calmodulin has been determined to lie at the putative basic alpha-helix region located around the src homology 3 (SH3) domain of NE-dlg/SAP102. Using a surface plasmon resonance measurement system, we detected specific binding of recombinant NE-dlg/SAP102 to the immobilized calmodulin with a Kd value of 44 nM. However, the binding of Ca2+/calmodulin to NE-dlg/SAP102 did not modulate the interaction between PDZ domains of NE-dlg/SAP102 and the C-terminal end of rat NR2B. We have also identified that the region near the calmodulin binding site of NE-dlg/SAP102 interacts with the GUK-like domain of PSD-95/SAP90 by two-hybrid screening. Pull down assay revealed that NE-dlg/SAP102 can interact with PSD-95/SAP90 in the presence of both Ca2+ and calmodulin. These findings suggest that the Ca2+/calmodulin modulates interaction of neuronal membrane-associated guanylate kinase proteins and regulates clustering of neurotransmitter receptors at central synapses.  (+info)

Properties of filament-bound myosin light chain kinase. (4/4572)

Myosin light chain kinase binds to actin-containing filaments from cells with a greater affinity than to F-actin. However, it is not known if this binding in cells is regulated by Ca2+/calmodulin as it is with F-actin. Therefore, the binding properties of the kinase to stress fibers were examined in smooth muscle-derived A7r5 cells. Full-length myosin light chain kinase or a truncation mutant lacking residues 2-142 was expressed as chimeras containing green fluorescent protein at the C terminus. In intact cells, the full-length kinase bound to stress fibers, whereas the truncated kinase showed diffuse fluorescence in the cytoplasm. After permeabilization with saponin, the fluorescence from the truncated kinase disappeared, whereas the fluorescence of the full-length kinase was retained on stress fibers. Measurements of fluorescence intensities and fluorescence recovery after photobleaching of the full-length myosin light chain kinase in saponin-permeable cells showed that Ca2+/calmodulin did not dissociate the kinase from these filaments. However, the filament-bound kinase was sufficient for Ca2+-dependent phosphorylation of myosin regulatory light chain and contraction of stress fibers. Thus, dissociation of myosin light chain kinase from actin-containing thin filaments is not necessary for phosphorylation of myosin light chain in thick filaments. We note that the distance between the N terminus and the catalytic core of the kinase is sufficient to span the distance between thin and thick filaments.  (+info)

cAMP inhibits translation by inducing Ca2+/calmodulin-independent elongation factor 2 kinase activity in IPC-81 cells. (5/4572)

Treatment of IPC-81 cells led to inhibition of protein synthesis, which was accompanied by an increase in the average size of polysomes and a decreased rate of elongation, indicating that it involved inhibition of peptide chain elongation. This inhibition was also associated with increased phosphorylation of elongation factor eEF2 (which inhibits its activity) and enhanced Ca2+/calmodulin-independent activity of eEF2 kinase. Previous work has shown that phosphorylation of eEF2 kinase by cAMP-dependent protein kinase (cAPK) in vitro induces such activator-independent activity, and the present data show that such a mechanism can occur in intact cells to link physiological levels of cAPK activation with inhibition of protein synthesis.  (+info)

T-cell stimulation through the T-cell receptor/CD3 complex regulates CD2 lateral mobility by a calcium/calmodulin-dependent mechanism. (6/4572)

T lymphocyte activation through the T cell receptor (TCR)/CD3 complex alters the avidity of the cell surface adhesion receptor CD2 for its ligand CD58. Based on the observations that activation-associated increases in intracellular [Ca2+] ([Ca2+]i) strengthen interactions between T cells and antigen-presenting cells, and that the lateral mobility of cell surface adhesion receptors is an important regulator of cellular adhesion strength, we postulated that [Ca2+]i controls CD2 lateral mobility at the T cell surface. Human Jurkat T leukemia cells were stimulated by antibody-mediated cross-linking of the TCR/CD3 complex. CD2 was labeled with a fluorescently conjugated monoclonal antibody. Quantitative fluorescence microscopy techniques were used to measure [Ca2+]i and CD2 lateral mobility. Cross-linking of the TCR/CD3 complex caused an immediate increase in [Ca2+]i and, 10-20 min later, a decrease in the fractional mobility of CD2 from the control value of 68 +/- 1% to 45 +/- 2% (mean +/- SEM). One to two hours after cell stimulation the fractional mobility spontaneously returned to the control level. Under these and other treatment conditions, the fraction of cells with significantly elevated [Ca2+]i was highly correlated with the fraction of cells manifesting significantly reduced CD2 mobility. Pretreatment of cells with a calmodulin inhibitor or a calmodulin-dependent kinase inhibitor prevented Ca2+-mediated CD2 immobilization, and pretreatment of cells with a calcineurin phosphatase inhibitor prevented the spontaneous reversal of CD2 immobilization. These data suggest that T cell activation through the TCR/CD3 complex controls CD2 lateral mobility by a Ca2+/calmodulin-dependent mechanism, and that this mechanism may involve regulated phosphorylation and dephosphorylation of CD2 or a closely associated protein.  (+info)

Suramin and suramin analogs activate skeletal muscle ryanodine receptor via a calmodulin binding site. (7/4572)

Contraction of skeletal muscle is triggered by the rapid release of Ca2+ from the sarcoplasmic reticulum via the ryanodine receptor/calcium-release channel. The trypanocidal drug suramin is an efficient activator of the ryanodine receptor. Here, we used high-affinity [3H]ryanodine binding to sarcoplasmic reticulum from rabbit skeletal muscle to screen for more potent analogs of suramin. This approach resulted in the identification of NF307, which accelerates the association rate of [3H]ryanodine binding with an EC50 = 91 +/- 7 microM at 0.19 microM calculated free Ca2+. In single-channel recordings with the purified ryanodine receptor, NF307 increased mean open probability at 0.6 microM Ca2+ from 0.020 +/- 0.006 to 0.53 +/- 0.07 with no effect on current amplitude and unitary conductance. Like caffeine, NF307 exerts a very pronounced Ca2+-sensitizing effect (EC50 of Ca2+ shifted approximately 10-fold by saturating NF307 concentrations). Conversely, increasing concentrations of free Ca2+ sensitized the receptor for NF307 (EC50 = 14.6 +/- 3.5 microM at 0.82 microM estimated free Ca2+). The effects of NF307 and caffeine on [3H]ryanodine binding were additive, irrespective of the Ca2+ concentration. In contrast, the effects of calmodulin, which activates and inhibits the ryanodine receptor in the absence and presence of Ca2+, respectively, and of NF307 were mutually antagonistic. If the purified ryanodine receptor was prebound to a calmodulin-Sepharose matrix, 100 microM NF307 and 300 microM suramin eluted the purified ryanodine receptor to an extent that was comparable to the effect of 10 microM calmodulin. We conclude that NF307 and suramin interact directly with a calmodulin binding domain of the ryanodine receptor. Because of its potent calcium-sensitizing effect, NF307 may represent a lead compound in the search of synthetic ryanodine receptor ligands.  (+info)

Dynamic and quantitative Ca2+ measurements using improved cameleons. (8/4572)

Cameleons are genetically-encoded fluorescent indicators for Ca2+ based on green fluorescent protein variants and calmodulin (CaM). Because cameleons can be targeted genetically and imaged by one- or two-photon excitation microscopy, they offer great promise for monitoring Ca2+ in whole organisms, tissues, organelles, and submicroscopic environments in which measurements were previously impossible. However, the original cameleons suffered from significant pH interference, and their Ca2+-buffering and cross-reactivity with endogenous CaM signaling pathways was uncharacterized. We have now greatly reduced the pH-sensitivity of the cameleons by introducing mutations V68L and Q69K into the acceptor yellow green fluorescent protein. The resulting new cameleons permit Ca2+ measurements despite significant cytosolic acidification. When Ca2+ is elevated, the CaM and CaM-binding peptide fused together in a cameleon predominantly interact with each other rather than with free CaM and CaM-dependent enzymes. Therefore, if cameleons are overexpressed, the primary effect is likely to be the unavoidable increase in Ca2+ buffering rather than specific perturbation of CaM-dependent signaling.  (+info)

TY - JOUR. T1 - Fluorescence analysis of calmodulin mutants containing tryptophan. T2 - Conformational changes induced by calmodulin-binding peptides from myosin light chain kinase and protein kinase II. AU - Prendergast, Franklyn G.. PY - 1991. Y1 - 1991. N2 - 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. The peptides RS20F and RS20CK correspond to CaM-binding amino acid sequence segments of either nonmuscle myosin light chain kinase (nmMLCK) or calmodulin-dependent protein kinase II (CaMPK-II), respectively. Both steady-state and time-resolved fluorescence data were collected from the various peptide-CaM complexes. Steady-state fluorescence intensity measurements indicated that, in the presence of an excess of ...
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 ...
Techniques such as X-ray structural analysis offer snapshots, at best, of steps in this intracellular work flow. But single-molecule atomic-force spectroscopy has opened a new window on such dynamic processes.. Professor Matthias Rief and colleagues at the Technische Universitaet Muenchen had previously shown that they could fix a single calmodulin molecule between a surface and the cantilever tip of a specially built atomic-force microscope, expose it to calcium ions in solution, induce peptide binding and unbinding, and measure changes in the molecules mechanical properties as it did its work. "What is special about our technique," Rief says, "is that we can work directly in aqueous solution. We can make our measurements in exactly the conditions under which the protein works in its natural environment. So we can directly observe how the calmodulin snatches the amino acid chain and folds itself, to hold its target fast." Measuring the force needed to bend the calmodulin molecule out of its ...
Elsewhere, we have reported the structure of a rat calmodulin gene and two distinct rat calmodulin cDNAs, pRCM1 and pRCM3. Here, I report the cloning and sequencing of the third calmodulin cDNA (pRCM4) and two additional rat calmodulin genes. The original calmodulin gene is named CaM I (pRCM1) and t …
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N-methyl-D-aspartate (NMDA) receptors are calcium-permeable ion channels assembled from four subunits that each have a common membrane topology. The intracellular carboxyl terminal domain (CTD) of each subunit varies in length, is least conserved between subunits, and binds multiple intracellular proteins. We defined a region of interest in the GluN2A CTD, downstream of well-characterized membraneproximal motifs, that shares only 29% sequence similarity with the equivalent region of GluN2B. GluN2A (amino acids 875-1029) was fused to GST and used as a bait to identify proteins from mouse brain with the potential to bind GluN2A as a function of calcium. Using mass spectrometry we identified calmodulin as a calcium-dependent GluN2A binding partner. Equilibrium fluorescence spectroscopy experiments indicate that Ca²⁺/calmodulin binds GluN2A with high affinity (5.2 ± 2.4 nM) in vitro. Direct interaction of Ca²⁺/calmodulin with GluN2A was not affected by disruption of classic sequence motifs ...
Involvement of calmodulin and calmodulin-like proteins in plant responses to abiotic stresses Published In Frontiers in Plant Science, 6:600, 2015, by Houqing Zeng, Luqin Xu, Amarjeet Singh, Huizhong Wang, Liqun Du, B. W. Poovaiah ...
TY - JOUR. T1 - Calmodulin binds to the C terminus of sodium channels Nav1.4 and Navl.6 and differentially modulates their functional properties. AU - Herzog, Raimund I.. AU - Liu, Chuanju. AU - Waxman, Stephen G.. AU - Cummins, Theodore R.. PY - 2003/9/10. Y1 - 2003/9/10. N2 - Modulation of voltage-gated sodium channels (VGSC) can have a major impact on cell excitability. Analysis of calmodulin (CaM) binding to GST-fusion proteins containing the C-terminal domains of Navl.l-Na vl.9 indicates that some of the tetrodotoxin-sensitive VGSC isoforms, including Navl.4 and Navl.6, are able to bind CaM in a calcium-independent manner. Here we demonstrate that association with CaM is important for functional expression of Nav1.4 and Navl.6 VGSCs. Disrupting the interaction between CaM and the C terminus of Na vl.4 and Navl.6 channels reduced current amplitude by 99 and 62%, respectively. Overexpression of CaM increased the current generated by Navl.4 and Navl.6 C-terminal mutant constructs that ...
The calcium-signaling network is an important transducer of internal and external stimuli in plants. These signals are transduced by a divers set of calcium-sensors such as calmodulin and calmodulin like proteins. In this work, AFG1L2 (AFG1 like protein 2) was characterized as a calmodulin binding protein that belongs to the family of AAA+ proteins (ATPases associated with various cellular activities). Using GFP fusion constructs it was possible to determine the in vivo localization of AFG1L2 in mitochondria and also to confirm the dual localization of a previously described homologe, AFG1L1, to mitochondria and chloroplasts. The interaction between AFG1L2 and calmodulin is calcium dependent and the calmodulin binding site of the AFG1L2 protein is in the AAA domain at a site homologous to the AFG1L1 protein, in very close proximity to the Walker A Motif, which is essential for ATP hydrolysis. It could be shown that ATP and ADP intensify the interaction between AFG1L2 and calmodulin. AAA-proteins ...
Mutations: The following mutations were used: Camn339, recessive RNA null mutation (Heimanet al. 1996); Cam7, recessive ethyl methanesulfonate mutation (Nelsonet al. 1997); Cam352, recessive hypomorph, generated by excision of a P element in 5′ flanking DNA (Scottet al. 1997); Cam3909, recessive hypomorph generated by a P insertion 60 bp 5′ of the transcription start site (Harvieet al. 1998); Ryr16, recessive mutation of the ryanodine receptor gene (Ryr; Sullivanet al. 2000); Df(2R)H3E1, deficiency with breakpoints at 44D1-4 and 44F12 (Bloomington Stock Center); Ca-α1DX7, embryonic lethal Ca-α1D mutation (Eberlet al. 1998); Ca-α1DAR66, hypomorphic Ca-α1D mutation (Eberlet al. 1998; Renet al. 1998); and cn1, cinnabar (Bloomington Stock Center).. Gal4 lines: We used the following Gal4 lines: 24B-Gal4, P{GawB}how24B, an insertion into held out wings that expresses Gal4 in muscle (Brand and Perrimon 1993); elav-Gal4, Gal4 expressed under the elav promoter in neurons at all developmental ...
The regulation of the guinea-pig pancreatic acinar plasma membrane Ca2+ pump by protein kinase A, protein kinase C and calmodulin was investigated. The results were compared with the effects of these regulators on the high affinity Ca2+-ATPase found in this membrane preparation. The catalytic subunit of cyclic AMP-dependent protein kinase stimulated Ca2+ transport 2-fold, but had no effect on Ca2+-dependent ATPase activity. Purified protein kinase C, the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate and diacylglycerol derivative, 1-stearoyl-2-arachidonoyl-sn-glycerol, failed to stimulate the Ca2+-uptake but augmented the Ca2+-dependent ATPase activity. Exogenously added calmodulin failed to stimulate either activity. In addition, two antagonists of calmodulin activity, trifluoperazine and compound 48/80 produced a concentration-dependent inhibition of Ca2+-transport. These data suggest the presence of endogenous calmodulin within guinea-pig pancreatic acinar plasma membranes. Both calmodulin
Biological systems primarily use proteins to sense and respond to other molecules. We sought to engineer a protein-based platform as the basis of a biologically emulative biosensor. This biosensor platform is especially powerful if both the analyte sensitivity and transduction method can be straightforwardly customized to respond to important targets. Here we show our attempts to demonstrate the modularity of a pre-existing protein biosensor through such customization. The calcium-binding protein calmodulin has already been engineered to exhibit enzymatic switching in response to peptide binding through fusion to a split TEM1 ß-lactamase. To extend this platform, we first evolved the calmodulin-ß-lactamase fusion (BlaCaM) to exhibit sensitivity to a previously inactive peptide, Staphylococcus aureus ∂-toxin, through random mutagenesis of the calmodulin portion of BlaCaM, followed by screening the purified library for ß-lactamase activity. Second, we altered the transduction domain by ...
Calmodulin (CaM) (an abbreviation for CALcium MODULated proteIN) is a calcium-binding protein expressed in all eukaryotic cells. It can bind to and regulate a number of different protein targets, thereby affecting many different cellular functions. Calmodulin 1 is one of nearly twenty human calmodulins.Calmodulinis the archetype of the family of calcium-modulated proteins of which nearly 20 members have been found. They are identified by their occurrence in the cytosol or on membranes facing the cytosol and by a high affinity for calcium. Calmodulin contains 148 amino acids and has 4 calcium-binding motifs. Its functions include roles in growth and the cell cycle as well as in signal transduction and the synthesis and release of neurotransmitters.
Transcription factor regulating the cell cycle specific transcription of a spindle pole body (SPB) calmodulin binding protein SPC110. Required for full induction of SPC110 transcription in late G1. Binds to DNA consensus sequence 5-[AT]AA[TC]AAACAA[AT]-3. Dosage dependent suppressor of calmodulin mutants which have specific defects in SPB assembly.
It is an open question how the multiple special and temporal scales involved in intracellular Ca2+ handling within the STDP models affect the plasticity outcomes predicted by these models. Hebbian or associative plasticity is triggered by postsynaptic Ca2+ influx which activates calmodulin and CaMKII. The influx of Ca2+ through voltage-dependent NMDA receptors and Ca2+ channels is regulated by Ca2+ -activated K+ channels (SK-channels) providing negative feedback regulation of postsynaptic [Ca2+]. Using 3-dimensional modelling of Ca2+ and calmodulin dynamics within dendritic spines we show that the non-linear relationship between Ca2+ influx and calmodulin activation endows SK-channels with the ability to "gate" calmodulin activation and therefore the induction of Hebbian synaptic plasticity. Since SK-channels are inhibited by several neuro-modulator receptors including acetylcholine and noradrenaline, the gating of synaptic plasticity by SK-channels could represent a common mechanism by which ...
It is an open question how the multiple special and temporal scales involved in intracellular Ca2+ handling within the STDP models affect the plasticity outcomes predicted by these models. Hebbian or associative plasticity is triggered by postsynaptic Ca2+ influx which activates calmodulin and CaMKII. The influx of Ca2+ through voltage-dependent NMDA receptors and Ca2+ channels is regulated by Ca2+ -activated K+ channels (SK-channels) providing negative feedback regulation of postsynaptic [Ca2+]. Using 3-dimensional modelling of Ca2+ and calmodulin dynamics within dendritic spines we show that the non-linear relationship between Ca2+ influx and calmodulin activation endows SK-channels with the ability to "gate" calmodulin activation and therefore the induction of Hebbian synaptic plasticity. Since SK-channels are inhibited by several neuro-modulator receptors including acetylcholine and noradrenaline, the gating of synaptic plasticity by SK-channels could represent a common mechanism by which ...
Background: Recent genetic studies identified mutations in CALM1 or CALM2, 2 of the 3 human genes encoding calmodulin (CaM), in both catecholaminergic polymorphic ventricular tachycardia (CPVT) and long QT syndrome (LQTS). CPVT is commonly caused by mutations in sarcoplasmic reticulum genes that increase diastolic Ca leakage through ryanodine receptor (RyR2) Ca relase channels, whereas LQTS is usually caused by dysfunctional plasma membrane ion channels. How mutant CaM causes either CPVT or LQTS is unknown.. Objective: To gain mechanistic insight into how CaM mutations cause divergent human arrhythmia phenotypes.. Methods and Results: We prepared recombinant wild-type (WT) and mutant CaM proteins associated with either CPVT (N54I, N98S) or LQTS ( F142L, D130G). LQTS CaM mutations drastically reduce Ca binding affinity to CaM, whereas CPVT mutations have either no effect (N54I) or slightly reduce Ca binding affinity (N98S). At physiological free CaM [100 nM] and Ca [120 nM], CPVT CaMs ...
In article ,95059.080316RJC8 at psuvm.psu.edu, Richard Cyr ,RJC8 at psuvm.psu.edu, writes: , Does anyone know of a reference wher , e the extinction coefficient of CaM was determined? The Merck index gives the extinction coefficient(1%) at A280 to be 2.1 Christine Dept. of Biochemistry hughe014 at mc.duke.edu ...
(1994) Means. FEBS Letters. Calcium and its ubiquitous intracellular receptor calmodulin are required for cell proliferation. Studies in a variety of model systems are beginning to identify components of the calcium/calmodulin cascade required for movement of quiescent cells into the cell cycle a...
The vacuolar calmodulin (CaM)-stimulated Ca2+-ATPase, BCA1p, in cauliflower (Brassica oleracea) has an extended N terminus, which was suggested to contain a CaM-binding domain (S. Malmstrom, P. Askerlund, M.G. Palmgren [1997] FEBS Lett 400: 324328). The goal of the present study was to determine the role of the N terminus in regulating BCA1p. Western analysis using three different antisera showed that the N terminus of BCA1p is cleaved off by trypsin and that the N terminus contains the CaM-binding domain. Furthermore, the expressed N terminus binds CaM in a Ca2+dependent manner. A synthetic peptide corresponding to the CaM-binding domain of BCA1p (Ala-19 to Leu-43) strongly inhibited ATP-dependent Ca2+ pumping by BCA1p in cauliflower low-density membranes, indicating that the CaM-binding region of BCA1p also has an autoinhibitory function. The expressed N terminus of BCA1p and a synthetic peptide (Ala-19 to Met-39) were good substrates for phosphorylation by protein kinase C. Sequencing of the ...
Structural and biophysical studies reveal how CaMKII kinases, which are important for cellular learning and memory, are switched on by binding of Ca2+/calmodulin.
Rabbit polyclonal Calmodulin (phospho T79 + S81) antibody validated for WB, ELISA, IHC, ICC/IF and tested in Human. Referenced in 2 publications. Immunogen…
Adunyah S.E.; Dean W.L., 1987: Regulation of human platelet membrane calcium transport by cyclic amp and calmodulin dependent phosphorylation
Ca2+-calmodulin binding to caldesmon and the caldesmon-actin-tropomyosin complex. Its role in Ca2+regulation of the activity of synthetic smooth-muscle thin filaments Academic Article ...
Many signalling pathways in plants are regulated by the second messenger calcium (Ca2+). In the standard model, Ca2+-sensor proteins, such as CaM (calmodulin), detect Ca2+ signals and subsequently regulate downstream targets to advance the signal transduction cascade. In addition to CaM, plants possess many CMLs (CaM-like proteins) that are predicted to function as Ca2+ sensors, but which remain largely uncharacterized. In the present study, we examined the biochemical properties, subcellular localization and tissue-specific distribution of Arabidopsis CML43. Our data indicate that CML43 displays characteristics typical of Ca2+ sensors, including high-affinity Ca2+ binding, conformational changes upon Ca2+ binding that expose hydrophobic regions and stabilization of structure in the presence of Mg2+ or Ca2+. In vivo localization analysis demonstrates that CML43 resides in cytosolic and nuclear compartments. Transgenic plants expressing a CML43:GUS (β-glucoronidase) promoter reporter gene ...
The limited ability of cytotoxic CD8+ T cells to infiltrate solid tumors and function within the tumor microenvironment presents a major roadblock to effective immunotherapy. Ion channels and Ca2+-dependent signaling events control the activity of T cells and are implicated in the failure of immune surveillance in cancer. Reduced KCa3.1 channel activity mediates the heightened inhibitory effect of adenosine on the chemotaxis of circulating T cells from head and neck squamous cell carcinoma (HNSCC) patients. Herein, we conducted experiments that elucidate the mechanisms of KCa3.1 dysfunction and impaired chemotaxis in HNSCC CD8+ T cells. The Ca2+ sensor calmodulin (CaM) controls multiple cellular functions including KCa3.1 activation. Our data showed that CaM expression is lower in HNSCC than healthy donor (HD) T cells. This reduction was due to an intrinsic decrease in the genes encoding CaM combined to the failure of HNSCC T cells to upregulate CaM upon activation. Furthermore, the reduction in CaM was
The RbcS genes encode the small subunits of rubisco; the expression of these genes is controlled in a light-dependent and independent manner. It has been reported that intracellular calmodulin (CaM) is involved in light-dependent RbcS expression. In this report, the role of extracellular CaM in regulating expression of RbcS in darkness was examined. The time course of expression of RbcS-GUS and that of the secretion of CaM in the suspended transgenic tobacco cells in darkness were very similar. Both showed initial increase followed by decline with maximum CaM secretion preceding maximum GUS expression by 24 h. The concentration of CaM in the culture medium is regulated light independently. Purified CaM alone added to the media enhanced RbcS-GUS expression in darkness. The addition of membrane-impermeable CaM inhibitors, such as anti-CaM antiserum or W7-agarose, repressed the expression of RbcS-GUS in darkness, but this inhibitory effect was completely reversed by adding exogenous purified CaM. ...
Forkhead Transcription Factor; Drives S-phase Specific Expression Of Genes Involved In Chromosome Segregation, Spindle Dynamics, And Budding; Suppressor Of Calmodulin Mutants With Specific SPB Assembly Defects; Telomere Maintenance Role; Regulates Replicative Lifespan; Ortholog Of C. Elegans Lifespan Regulator PHA-4
Protein interactions animation. Clip 10 of 10. Final clip in an animation sequence showing protein interactions within a dividing cell. This clip, which includes labels, shows an actin-myosin bundle (right) forming part of the contractile ring at the periphery of the cell. Proteins (left) are in the surrounding cytoplasm, including those that activate the contractile ring. This contraction (a form of cytokinesis) is initiated by a wave of calcium ions (see K003/3843). Here, the heads of the myosin filaments (dark) are wrapped around the actin filaments (light) and pulling them. The full sequence of ten clips shows the interaction between the protein calmodulin (CaM, calcium-modulated protein), calcium ions, the MLCK (myosin light-chain kinase) protein, and the actin-myosin bundles of the cells cytoskeleton, resulting in contraction of the membrane and cell division. For the entire sequence, see clips K003/3847 to K003/3838. For the same sequence as an anaglyph 3D animation, see clips K003/4492 to K003
Authors: Bertini, Ivano; Luchinat, Claudio; Parigi, Giacomo; Yuan, Jing. Citation: Bertini, Ivano; Kursula, Petri; Luchinat, Claudio; Parigi, Giacomo; Vahokoski, Juha; Wilmanns, Matthias; Yuan, Jing. "Accurate Solution Structures of Proteins from X-ray Data and a Minimal Set of NMR Data: Calmodulin-Peptide Complexes As Examples" J. Am. Chem. Soc. 131, 5134-5144 (2009).. Assembly members: ...
Calmodulin (CaM) is a ubiquitous calcium-binding protein responsible for the binding and activation of a vast number of enzymes and signaling pathways. It contains two lobes that bind two calcium ions each, separated by a flexible central linker. This structural flexibility allows CaM to bind and regulate a large number of diverse protein targets within the cell in response to Ca2+ gradients. Voltage gated calcium channels (CaVs), as main sources of extracellular Ca2+, are crucial for a number of physiological processes, from muscle contraction to neurotransmission and endocrine function. These large transmembrane proteins open in response to membrane depolarization and allow gated entry of Ca2+ ions into the cytoplasm. Their regulation is currently the subject of intense investigation due to its pharmacological and scientific importance. CaM has been previously shown to pre-associate and act as a potent inhibitor of one class of high-voltage activated (HVA) channels called L-type channels via ...
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
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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...
Ca(2+)-dependent inactivation (CDI) of L-type Ca(2+) channels plays a critical role in controlling Ca(2+) entry and downstream signal transduction in excitable cells. Ca(2+)-insensitive forms of calmodulin (CaM) act as dominant negatives to prevent CDI, suggesting that CaM acts as a resident Ca(2+) sensor. However, it is not known how the Ca(2+) sensor is constitutively tethered. We have found that the tethering of Ca(2+)-insensitive CaM was localized to the C-terminal tail of alpha(1C), close to the CDI effector motif, and that it depended on nanomolar Ca(2+) concentrations, likely attained in quiescent cells. Two stretches of amino acids were found to support the tethering and to contain putative CaM-binding sequences close to or overlapping residues previously shown to affect CDI and Ca(2+)-independent inactivation. Synthetic peptides containing these sequences displayed differences in CaM-binding properties, both in affinity and Ca(2+) dependence, leading us to propose a novel mechanism for ...
View mouse Camta1 Chr4:151059525-151861876 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
I need an online or downloadable hydropathy plot programme. But I need something special! I want a programme that takes into account the presence or absence of non-covalent modifications, especially phosphorylation sites and calmodulin binding sites. Any suggestions? If so, please email me at: o.s.depeyer at reading.ac.uk ...
85. Assessment of Foreign Qualifications Act, cf. Consolidation Act No. 74 of 24 January 2003, with the amendments following from Act No. 315 of 30 March 2007, (2007).. ...
Myc-DDK-tagged ORF clone of Homo sapiens calmodulin-like 4 (CALML4), transcript variant 1 as transfection-ready DNA - 10 µg - OriGene - cdna clones
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TY - JOUR. T1 - Phosphorylation of smooth muscle myosin light chain kinase by Ca2+/calmodulin-dependent protein kinase II. T2 - Comparative study of the phosphorylation sites. AU - Hashimoto, Yoshiaki. AU - Soderling, Thomas. PY - 1990. Y1 - 1990. N2 - Smooth muscle myosin light chain kinase (MLC-kinase) was rapidly phosphorylated in vitro by the autophosphorylated form of Ca2+/calmodulin-dependent protein kinase II (CaM-kinase II) to a molar stoichiometry of 2.77 ± 0.15 associated with a threefold increase in the concentration of calmodulin (CaM) required for half-maximal activation of MLC-kinase. Binding of CaM to MLC-kinase markedly reduced the phosphorylation stoichiometry to 0.21 ± 0.05 and almost completely inhibited phosphorylation of sites in two peptides (32P-peptides P1 and P2) with reduced phosphorylation of peptide P3. By analogy, cAMP-dependent protein kinase phosphorylated MLC-kinase to a stoichiometry of 3.0 or greater in the absence of CaM with about a threefold decrease in the ...
We report the identification and characterization of myr 4 (myosin from rat), the first mammalian myosin I that is not closely related to brush border myosin I. Myr 4 contains a myosin head (motor) domain, a regulatory domain with light chain binding sites and a tail domain. Sequence analysis of myosin I head (motor) domains suggested that myr 4 defines a novel subclass of myosin Is. This subclass is clearly different from the vertebrate brush border myosin I subclass (which includes myr 1) and the myosin I subclass(es) identified from Acanthamoeba castellanii and Dictyostelium discoideum. In accordance with this notion, a detailed sequence analysis of all myosin I tail domains revealed that the myr 4 tail is unique, except for a newly identified myosin I tail homology motif detected in all myosin I tail sequences. The Ca(2+)-binding protein calmodulin was demonstrated to be associated with myr 4. Calmodulin binding activity of myr 4 was mapped by gel overlay assays to the two consecutive light ...
The effect of calmodulin on the order of lipids in rhodopsin-free and rhodopsin-containing membranes has been studied using spin-label electron spin resonance methods. Calmodulin, up to 10(-6)M, did not change the measured order of lipids in bilayer membranes containing only rhodopsin. However, for bovine rod outer segment disc membranes, which contain rhodopsin and other proteins, calmodulin induced a significant concentration and temperature dependent increase in the order of the membrane lipids. This suggests that the site of calmodulin binding is remote from rhodopsin itself, and the nature of the binding appears to be a membrane surface phenomenon.
The Munc13 proteins are the key mediators of synaptic vesicle priming, an essential step in Ca2+-regulated neurotransmitter release that renders docked vesicles fusion-competent prior to exocytosis. They have emerged as important regulators of adaptive synaptic mechanisms such as presynaptic short-term plasticity, a process by which the release of neurotransmitter is dynamically adapted to a changing demand. Indeed, Munc13-1 and ubMunc13-2 contain a conserved calmodulin (CaM) binding site and the Ca2+-dependent interaction of these Munc13 isoforms with CaM constitutes a molecular mechanism that transduces residual Ca2+ signaling to the synaptic exocytotic machinery. This study aimed to (i) establish whether such regulation through CaM exists in the other Munc13 isoforms, bMunc13-2 and Munc13-3, and (ii) provide structural insights into the Munc13-CaM interaction. Bioinformatic tools were used to identify potential CaM recognition motifs in the non-conserved sequences of bMunc13-2 and Munc13-3. ...
Changes in calmodulin (CaM) mRNA and protein were investigated in aleurone layers of barley (Hordeum vulgare L. cv Himalaya) incubated in the presence and absence of calcium, gibberellic acid (GA3), and abscisic acid (ABA). CaM mRNA levels increased rapidly and transiently following incubation of aleurone layers in H2O, CaCl2, or GA3. The increase in CaM mRNA was prevented by ABA. This increase in CaM mRNA was brought about by physical stimulation during removal of the starchy endosperm from the aleurone layer. CaM protein levels did not increase in response to physical stimulation. Only incubation in GA3 plus CaCl2 brought about a rapid increase in CaM protein levels in the aleurone cell. ABA reduced the level of CaM protein below that found at the beginning of the incubation period. The rise in CaM protein preceded increases in the synthesis and secretion of [alpha]-amylase. Immunocytochemistry with monoclonal antibodies to carrot and mung bean CaM was used to localize CaM in aleurone ...
TY - JOUR. T1 - Degradation of PEP-19, a calmodulin-binding protein, by calpain is implicated in neuronal cell death induced by intracellular Ca2+ overload. AU - Kanazawa, Y.. AU - Makino, M.. AU - Morishima, Y.. AU - Yamada, K.. AU - Nabeshima, T.. AU - Shirasaki, Y.. PY - 2008/6/23. Y1 - 2008/6/23. N2 - Excessive elevation of intracellular Ca2+ levels and, subsequently, hyperactivation of Ca2+/calmodulin-dependent processes might play an important role in the pathologic events following cerebral ischemia. PEP-19 is a neuronally expressed polypeptide that acts as an endogenous negative regulator of calmodulin by inhibiting the association of calmodulin with enzymes and other proteins. The aims of the present study were to investigate the effect of PEP-19 overexpression on cell death triggered by Ca2+ overload and how the polypeptide levels are affected by glutamate-induced excitotoxicity and cerebral ischemia. Expression of PEP-19 in HEK293T cells suppressed calmodulin-dependent signaling and ...
Unloaded shortening velocity, a mechanical parameter associated with the rate of cross-bridge cycling, was investigated in chemically skinned guinea pig taenia coli and hog carotid artery. Shortening velocity was measured by the technique described by Edman, whereby large length steps are rapidly imposed on the muscle and the time under unloaded conditions is determined from the isometric myograms. Shortening velocity determined in this manner was similar to Vmax from the Hill force-velocity relations reported for both living and skinned taenia coli, and, in the case of carotid artery, was at least as large as that reported for living muscle. The behavior of shortening velocity was qualitatively similar for both preparations. Shortening velocity was strongly temperature dependent, with a Q10 of approximately 3.6. Shortening velocity was found to be dependent on both the Ca++ and calmodulin concentration. In contrast to the dependence of isometric force on Ca++-calmodulin, shortening velocity ...
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DNA-binding activity of a maize heat shock transcription factor (HSF) was induced by heat shock of a whole cell extract at 44°C. Addition of the calcium ion chelator EGTA reduced the binding of the HSF to heat shock element (HSE) in vitro. Re-addition of CaCl2 to the sample pretreated with EGTA restored the ability of the HSF to bind to DNA. DNA-binding activity of the HSF was also induced by directly adding CaCl2 to a whole cell extract at non-heat-shock temperature, but not by MgCl2. During HS at 44°C, calmodulin (CaM) antagonists chlorpromazine (CPZ) and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W7) inhibited DNA-binding activity of the HSF in a concentration-dependent manner, but N-(6-aminohexyl)-1-naphthalenesulfonamide (W5), an inactive structural analogue of W7, did not. Addition of antiserum specific to CaM reduced the binding of the HSF to HSE. Re-addition of CaM to the sample pretreated with antiserum could restore the binding activity of the HSF. DNA-binding activity of ...
Molecular dynamics (MD) simulation techniques have been employed to investigate structure and function relationships in cell motility proteins at atomic resolution. (1) To analyze motions in cell motility proteins an algorithm is described to identify and visualize the movements of rigid domains about common hinges in proteins. In comparing two structures, the method partitions a protein into domains of preserved geometry and characterizes the relative movement of domains by effective rotation axes. (2) Simulated in solution, the calcium-binding protein calmodulin exhibits large conformational changes on the nanosecond time scale. The central a-helix, which has been shown to unwind locally upon binding of calmodulin to target proteins, bends and unwinds near residue Arg74. The major structural change is a reorientation of the two Ca2+-binding domains with respect to each other and a rearrangement of α-helices in the N-terminus domain which make the hydrophobic target peptide binding site more ...
Problem statement: The present study was performed to determine the effect of Intracerebroventricular (ICV) administration of W-7, a specific calmodulin inhibitor, on the analgesic effect and development of tolerance to antinociceptive effect of acute and chronic morphine administration respectively. Approach: This study was carried out on male wistar rats, weighing 200-250 g. For acute experimental protocol, Morphine was injected intraperitonealy in a single dose (5 mg kg-1). For chronic experimental protocol, Morphine was administered daily (15 mg kg-1 for 8 days). The threshold to thermal nociceptive stimuli was measured by tail-flick test. In acute and chronic experiments, W-7 (0.25, 0.5 and 1 μmol/rat) was injected through ICV at different paradigms. Maximal Possible Effect percentage (MPE%) was considered as analgesia index. Results: Our result showed that W-7 (0.25, 0.5 and 1 μmol/rat) injections before acute morphine administration significantly reduced the analgesic effect of
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
Sequence searching (5) revealed that 14 of the 39 calmodulin-binding proteins contain a motif whose consensus is (I/L)QXXK(K/X)GB, where X is any residue and B is a basic residue (Fig. 2B). A related sequence in myosins, IQXXXXKXXXR, has been shown previously to bind calmodulin (18). Thus, we demonstrate that the domain is found in many calmodulin-binding proteins. Presumably the other targets that lack this motif have other calmodulin-binding sequences (10).. In addition to the calmodulin-binding targets, we also identified one protein, Pyc1p, that bound Cy3-labeled streptavidin. Pyc1p encodes a pyruvate carboxylase 1 homolog that contains a highly conserved biotin attachment region (19). Thus, as predicted by its sequence, Pyc1p is biotinylated in vivo. With appropriate detection assays, we expect that proteome chips can identify many types of posttranslational modification of proteins.. To test whether proteome chips could be used to identify activities that might not be accessible by other ...
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David Yue and colleagues report in the the current issue of Cell a surprising role for Ca2+-unbound apopcalmodulin in regulating calcium and sodium channel activities. The Ca2+-free form of calmodulin (apoCaM) often appears inert, modulating target molecules only upon conversion to its Ca2+-bound form. This schema has appeared to govern voltage-gated Ca2+ channels, where apoCaM has been considered a dormant Ca2+ sensor, associated with channels but awaiting the binding of Ca2+ ions before inhibiting channel opening to provide vital feedback inhibition. Using single-molecule measurements of channels and chemical dimerization to elevate apoCaM, we find that apoCaM binding on its own markedly upregulates opening, rivaling the strongest forms of modulation. Upon Ca2+ binding to this CaM, inhibition may simply reverse the initial upregulation. As RNA-edited and -spliced channel variants show different affinities for apoCaM, the apoCaM-dependent control mechanisms may underlie the functional diversity ...
Activation-induced cytidine deaminase (AID) is the key mutagenic enzyme that initiates somatic hypermutation (SH) and class switch recombination (CSR) by deaminating cytosine to uracil. The targeting of AID and therefore SH and CSR to Ig genes is a central process of the immune system, but the trans-acting factors mediating the specific targeting have remained elusive. Here we show that defective calmodulin inhibition of the transcription factor E2A after activation of the B cell receptor (BCR) leads to reduced BCR, IL4 plus CD40 ligand stimulated CSR to IgE and instead CSR to other Ig classes. AID that initiates CSR is shown to be in a complex with the transcription factors E2A, PAX5 and IRF4 on key sequences of the Igh locus. Calmodulin shows proximity with each of them after BCR stimulation. BCR signaling reduces binding of the proteins to some of the target sites on the Igh locus, and calmodulin resistance of E2A blocks these reductions. AID binds directly to the bHLH domain of E2A and to ...
Calcium-calmodulin (CaM) binding to the epidermal growth factor receptor (EGFR) has been shown to both inhibit and stimulate receptor activity. CaM binds to the intracellular juxtamembrane (JM) domain (Met645-Phe688) of EGFR. Protein kinase C (PKC) mediated phosphorylation of Thr654 occurs within this domain. CaM binding to the JM domain inhibits PKC phosphorylation and conversely PKC mediated phosphorylation of Thr654 or Glu substitution of Thr654 inhibits CaM binding. A second threonine residue (Thr669) within the JM domain is phosphorylated by the mitogen-activated protein kinase (MAPK). Previous results have shown that CaM interferes with EGFR-induced MAPK activation. If and how phosphorylation of Thr669 affects CaM-EGFR interaction is however not known.In the present study we have used surface plasmon resonance (BIAcore) to study the influence of Thr669 phosphorylation on real time interactions between the intracellular juxtamembrane (JM) domain of EGFR and CaM. The EGFR-JM was expressed as ...
Background Calmodulin (CaM) plays an important role in Ca2+-dependent signal transduction. Ca2+ binding to CaM triggers a conformational change, forming a hydrophobic patch that is important for target protein recognition. CaM regulates a Ca2+-dependent inactivation process in store-operated Ca2+entry, by interacting Orai1. To understand the relationship between Ca2+-induced hydrophobicity and CaM/Orai interaction, chimera proteins constructed by exchanging EF-hands of CaM with those of Troponin C (TnC) are used as an informative probe to better understand the functionality of each EF-hand. Results ANS was used to assess the context of the induced hydrophobic surface on CaM and chimeras upon Ca2+ binding. The exchanged EF-hands from TnC to CaM resulted in reduced hydrophobicity compared with wild-type CaM. ANS lifetime measurements indicated that there are two types of ANS molecules with rather distinct fluorescence lifetimes, each specifically corresponding to one lobe of CaM or chimeras.
The effect of Ca2+ and calmodulin on phosphorylation of islet secretory granule proteins was studied. Secretory granules were incubated in a phosphorylation reaction mixture containing [32P]ATP and test reagents. The 32P-labeled proteins were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the 32P content was visualized by autoradiography, and the relative intensities of specific bands were quantitated. When the reaction mixture contained EGTA and no added Ca2+, 32P was incorporated into two proteins with molecular weights of 45,000 and 13,000. When 10−4 M Ca2+ was added without EGTA, two additional proteins (58,000 and 48,000 Mr) were phosphorylated, and the 13,000-Mr protein was absent. The addition of 2.4 μM calmodulin markedly enhanced the phosphorylation of the 58,000- and 48,000-Mr proteins and resulted in the phosphorylation of a major protein whose molecular weight (64,000 Mr) is identical to that of one of the calmodulin binding proteins located on the granule ...
BACKGROUND: In contrast to conventional muscle myosins, where two different light chains (LCs) stabilize the elongated regulatory domain (RD) region of the head portion of the molecule, unconventional myosins are a diverse group of motors in which from one to six calmodulin (CaM) subunits are bound tandemly to the RD. In both cases, the heavy chains of the RDs have special sequences called "IQ motifs to which the LCs or CaM bind. A previously puzzling aspect of certain unconventional myosins is their unusual mode of regulation, where activation of motility occurs at low levels of Ca2+. Although the atomic structure of the conventional muscle myosin RD has been determined, no crystallographic structure of the RD of an unconventional myosin is yet available. RESULTS: We have constructed a model of vertebrate CaM bound to the first IQ motif present in the neck region of an unconventional myosin (chicken brush border myosin I), using strict binding rules derived from the crystal structure of the ...
Numerous investigations reported that increases of internal Ca2+ (Ca2+i) pivotally regulate high voltage-activated (HVA) Ca2+ channels via calmodulin (CaM). However, it is largely elusive that Ca2+i can regulate low voltage-activated T-type Ca2+ channels. Using whole cell patch clamp, we compared the biophysical properties of Ca2+ current through T-type Ca2+ channel Cav3.1, Cav3.2, or Cav3.3 stably expressed in HEK293 cells between internal solutions containing 27 nM and l μM free Ca2+. Both activation and inactivation kinetics of Cav3.3 current in l μM Ca2+i solution were more rapid than those of Cav3.3 in 27 nM Ca2+i solution. In addition, both activation and steady-state inactivation curves of Cav3.3 were negatively shifted in the higher Ca2+i solution. In contrast, the biophysical properties of Cav3.1 and Cav3.2 isoforms were not different between the two internal solutions. Overexpression of CaM1234 (calmodulin mutant lacking 4 Ca2+ binding sites) strongly suppressed the effects of l μM ...
A number of mouse and rat cells and their virus-transformed counterparts were tested for sensitivity to Pseudomonas aeruginosa exotoxin A (PEA). In each case, the transformed cells were considerably less sensitive than were the nontransformed cells. In the presence of trifluoperazine, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, or retinoic acid, the transformed cells became as sensitive as the nontransformed cells, whereas these drugs had little or no effect on the sensitivity to PEA of the nontransformed cells. Temperature-sensitive virus-transformed normal rabbit kidney cells were sensitized to PEA by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, when these cells were grown as the transformed phenotype, whereas the nontransformed phenotype could not be sensitized. The possibility is discussed that upon malignant transformation a process which is dependent upon calmodulin or protein kinase C strongly decreases the sensitivity of the cells to PEA.. ...
Read "Two isoforms of glutamate decarboxylase in Arabidopsis are regulated by calcium/calmodulin and differ in organ distribution, Plant Molecular Biology" on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
Typically hippocampal long-term potentiation (LTP) of synaptic strength requires Ca2+/calmodulin(CaM)-dependent Bibf1120 protein kinase II Bibf1120 (CaMKII) and Bibf1120 other kinases while long-term depression (LTD) requires phosphatases. This differential rules triggered GluA1 S831 to become well-liked by LTP-type stimuli (solid but short) while GluA1 S567 was well-liked by LTD-type stimuli (fragile but long term). Thus dependence on autonomous CaMKII in opposing types of plasticity requires specific substrate classes that are differentially controlled to allow stimulus-dependent substrate-site choice. Intro LTD and LTP trigger long-term adjustments Bibf1120 of synaptic power in reverse directions; both are Ca2+- reliant may appear at the same hippocampal CA3 to CA1 synapses and so are together considered to underlie learning memory space and cognition (for review discover (Collingridge et al. 2010 Carry and Malenka 2004 Martin et al. 2000 Xia and Surprise 2005 Twenty-five many years of study ...
When membrane potential is depolarized, intracellular Ca2+ beneath the plasma membrane of cardiac myocytes increases. Ca2+ binds to CaM and Ca2+/CaM complex leads to the facilitation of RGS action to accelerate hydrolysis of GKα-GTP to GKα-GDP. GKα-GDP binds free Gβγ to form trimeric G proteins, which therefore decreases the number of free Gβγ and thus the number of available KG channels at depolarized potentials. The time-dependent increase in KG current on hyperpolarization can then be interpreted as the reflection of the reverse reactions of these events, ie, less Ca2+ influx, less Ca2+/CaM, lesser activity of RGS, and more available Gβγ.. There still remain, however, two major questions in this reaction scheme. The first one is how Ca2+/CaM facilitates RGS action. It was reported that Ca2+/CaM binds RGS but does not change its GTPase accelerating activity in vitro.14 Therefore, some mechanisms other than direct facilitating action of Ca2+/CaM on the GTPase-accelerating function of ...
4J9Z: Unstructured to structured transition of an intrinsically disordered protein peptide in coupling Ca2+-sensing and SK channel activation.
Calcium-dependent, calmodulin-stimulated protein phosphatase. This subunit may have a role in the calmodulin activation of calcineurin.
The effects of extracellularly applied 3′-5′ cyclic guanosine monophosphate (cGMP) on kainate responses from cultured cerebellar granule and Purkinje neurons were investigated using whole-cell and outside-out patch recording modes. Cerebellar granule cell responses to kainate were not homogeneous, nor were the effects of cGMP. Therefore, effects of cGMP are described for two groups of granule cells categorized on the basis of the underlying channel conductance estimated by variance analysis. Cells with high-noise kainate responses had average channel conductances of 5 to 7 picoseimens, whereas the average conductances of low-variance noise responses were 0.3 to 2.0 picoseimens. High-noise kainate responses were inhibited by externally applied cGMP (5-1000 μM) in a rapidly reversible and dose-dependent manner. IC50 values were estimated at ∼150 μM cGMP for 25 μM kainate and ∼500 μM cGMP for 100 μM kainate. Evidence that cGMP-mediated inhibition of high-noise kainate responses ...
Ubiquitination was surprising because tBid-N has no lysine residues that conventionally act as ubiquitin acceptor sites (Fig. S1 B). Typically, ubiquitin can be linked either via a peptide bond to the ε amino group of a lysine residue or to the α amino group of an N-terminal residue (Ciechanover and Ben-Saadon, 2004). Because linkage to lysine was excluded, we investigated whether the N terminus of tBid-N acted as a ubiquitin acceptor site. To this end, tBid-N was fused C-terminally to a tandem affinity purification (TAP) tag, which contains a calmodulin-binding domain and protein A sequence separated by a tobacco etch virus (TEV) protease-sensitive site (ENLYFQG). This allows for two-step purification; first on IgG beads and then after cleavage by TEV on calmodulin beads (Rigaut et al., 1999). In one tBid-N TAP construct (TEV tBid-N TAP 7), sequences encoding the first seven amino acids of tBid-N and a TEV protease site were cloned upstream of the tBid-N coding region (Fig. 3 C). If tBid-N ...
Glioblastoma multiforme is a fatal malignancy of the central nervous system, demanding new methods of treatment. The combination of a calmodulin antagonist with bleomycin has shown synergistic activity in several preclinical models and has been evaluated in a Phase I clinical trial. Since phenothiazines reach high concentrations in the central nervous system, and bleomycin has been reported to have antitumoral activity as well, we studied this combination in a Phase II clinical trial. In addition, we purified calmodulin from normal brain and malignant gliomas to determine its biochemical and pharmacological characteristics. Seventeen patients were entered onto this study and all were evaluable. There were no partial or complete responses. There was one case of fatal pulmonary toxicity in a patient showing an objective tumor response. Otherwise, the treatment was well tolerated. Calmodulin purified from the normal brain and gliomas of patients undergoing resection was identical to each other and ...
We identified and analyzed 33 and 29 IQD1-like genes in Arabidopsis thaliana and Oryza sativa, respectively. The encoded IQD proteins contain a plant-specific domain of 67 conserved amino acid residues, referred to as the IQ67 domain, which is characterized by a unique and repetitive arrangement of three different calmodulin recruitment motifs, known as the IQ, 1-5-10, and 1-8-14 motifs. We demonstrated calmodulin binding for IQD20, the smallest IQD protein in Arabidopsis, which consists of a C-terminal IQ67 domain and a short N-terminal extension. A striking feature of IQD proteins is the high isoelectric point (~10.3) and frequency of serine residues (~11%). We compared the Arabidopsis and rice IQD gene families in terms of gene structure, chromosome location, predicted protein properties and motifs, phylogenetic relationships, and evolutionary history. The existence of an IQD-like gene in bryophytes suggests that IQD proteins are an ancient family of calmodulin-binding proteins and arose ...
We identified and analyzed 33 and 29 IQD1-like genes in Arabidopsis thaliana and Oryza sativa, respectively. The encoded IQD proteins contain a plant-specific domain of 67 conserved amino acid residues, referred to as the IQ67 domain, which is characterized by a unique and repetitive arrangement of three different calmodulin recruitment motifs, known as the IQ, 1-5-10, and 1-8-14 motifs. We demonstrated calmodulin binding for IQD20, the smallest IQD protein in Arabidopsis, which consists of a C-terminal IQ67 domain and a short N-terminal extension. A striking feature of IQD proteins is the high isoelectric point (~10.3) and frequency of serine residues (~11%). We compared the Arabidopsis and rice IQD gene families in terms of gene structure, chromosome location, predicted protein properties and motifs, phylogenetic relationships, and evolutionary history. The existence of an IQD-like gene in bryophytes suggests that IQD proteins are an ancient family of calmodulin-binding proteins and arose ...
Glycoprotein (GP)VI (≈65 kDa) is a member of the immunoglobulin (Ig) superfamily, with two extracellular Ig domains, a mucin-like domain, transmembrane domain, and cytoplasmic tail.5,6 In addition to the major physiological ligand, collagen, GPVI also binds laminin55 and nonphysiological ligands including cross-linked collagen-related peptide (CRP) and the snake toxins, convulxin, and alborhagin, which bind at overlapping but distinct binding-sites within the extracellular Ig domains.56-58 GPVI signals by Fc receptor γ-chain (FcRγ)-dependent and FcRγ-independent pathways5,6,59-61: the former involves an immunoreceptor tyrosine-based activation motif (ITAM) in the cytoplasmic tail of FcRγ, whereby ligand-induced cross-linking of GPVI/FcRγ leads to activation of the ITAM-dependent Syk kinase; this involves direct interaction of Src family kinases, Fyn and Lyn, with a consensus Pro-rich sequence in the GPVI cytoplasmic tail,62 whereas a juxtamembrane calmodulin-binding sequence is involved ...
Matrix enzymes are imported into peroxisomes and glyoxysomes, a subclass of peroxisomes involved in lipid mobilization. Two peroxisomal targeting signals (PTS), the C-terminal PTS1 and the N-terminal
Malca Chen-Zion, Ph.D., is a Clinical and Regulatory Consultant for the Medical Industry. Malca Chen-Zion Consulting Group provides clinical and regulatory consulting services related to the research and development of medical devices and related technologies.
1MXE: Structure of the Complex of Calmodulin with the Target Sequence of Calmodulin-Dependent Protein Kinase I: Studies of the Kinase Activation Mechanism
M. Dettmann, V. Herrig, J. Maldonis, J. Neuhaus, D. Shrestha, P. Rajbhandari, Z. Thune, M. Been, M. Martinez-Szewczyk, V. Khristenko, Y. Onel and U. Akgun, "Radiation Hard Elastomer Scintillators for a New Generation of Particle Detectors", JINST 23 P0716, Journal of Instrumentation, 2017. L.K. Balcziak, T. H. Bach, L.R. Montgomery, M. E. Warwick, and U. Akgun, "Calmodulin Bound Aquaporin-0 Reveals Two Distinct Energy Profiles" Computational Molecular Bioscience, 6, 66-79, 2016. I.J. Tillman, M.A. Dettmann, V. Herrig, Z.L. Thune, A.J. Zieser, S.F. Michalek, M.O. Been, M.M. Martinez-Szewczyk, H.J. Koster, C.J. Wilkinson, M.W. Kielty, L.G. Jacobsohn, U. Akgun"High-Density Scintillating Glasses For A Proton Imaging Detector" http://dx.doi.org/10.1016/j.optmat.2016.10.015, Journal of Optical Materials, 2016. F. Duru, D. Baker, J. Schletzbaum, P. Bruecken, Y. Onel, A. Konik and U. Akgun, "Post Situ Neutron and Gamma Radiation Damage Tests on Different Quartz Types", JINST 11 T10006,Journal of ...
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:. ...
Norways National Research Center in Complementary and Alternative Medicine (NAFKAM) is organized as a center at the Faculty of Medicine, at UiT The Arctic University of Norway ...
The goal of the input team is to improve the binding and switching activity of the BlaCaM protein with respect to a previously non-functional analyte. A successful evolution would demonstrate the ability of the BlaCaM switch to sense different molecules, highlighting its potential as a biosensor component. BlaCaM is a fusion of two proteins, a calmodulin center with two halves of β-lactamase attached to the N- and C-termini. Calmodulin displays large conformational changes when it binds to both calcium and varying peptides. These conformational changes adjust the position of the two β-lactamase halves relative to each other, greatly affecting the activity of the enzyme. The ability to turn on or off the activity of the attached enzyme depending on the presence of an analyte gives the BlaCaM protein the ability to act as a sensor. By evolving BlaCaM to bind to different peptides or small molecules, the protein can be made into a sensor for a wide array of compounds. Adapting the BlaCaM switch ...
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
connectin: cell surface protein which binds both laminin & actin; binds thick filaments to Z lines in frog skeletal muscle; see also record for mini-titin which is a similar protein from invertebrates; titin has a protein kinase domain and a calmodulin-binding site near the C-terminus
(2004) Luoni et al. FEBS Letters. Type IIB Ca2+-ATPases have a terminal auto-inhibitory, domain the action of which is suppressed by calmodulin (CaM) binding. Here, we show that a peptide (6His-1M-I116) corresponding to the first 116 aminoacids (aa) of At-ACA8, the first cloned isoform of Arabido...
We have used a constitutively active mutant of the α2A-AR stably expressed in CHO-K1 cells to examine mechanisms of α2A-AR signaling. From these studies, at least three new conclusions can be drawn. First, the α2A-AR T373K has enhanced signaling to both Gi and Gs. Second, the inverse efficacy of a series of α2-AR antagonists is examined, and a novel difference between idazoxan and methyl-idazoxan (RX821002) has been found. This point is important for interpreting physiological studies that use these two compounds. Finally, the fraction of active α2A-AR for the T373K CAM mutant is approximately 50% for our whole cell cAMP accumulation assay, whereas the WT receptor appears to have a very low percentage of receptor active in the absence of agonist.. The effects of constitutively active receptor mutants on different G proteins are not always concordant as reported for the α1-AR by Perez et al. (1996). Ren et al. (1993)previously showed for the α2A-AR that the T373K mutation adjacent to TM6 ...
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Professional guide for Trifluoperazine Hydrochloride. Includes: pharmacology, pharmacokinetics, contraindications, interactions, adverse reactions and more.
Wondering how to take trifluoperazine? This eMedTV resource features helpful instructions for those who are starting treatment. It also talks about drug interactions, factors affecting your dose, and what to do if you take too much.
Professional guide for Trifluoperazine. Includes: pharmacology, pharmacokinetics, contraindications, interactions, adverse reactions and more.
Background Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein...
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SWISS-MODEL Template Library (SMTL) entry for 1l7z.1. Crystal structure of Ca2+/Calmodulin complexed with myristoylated CAP-23/NAP-22 peptide
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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 ...
Nakai A, Nagasaka A, Hidaka H, Tanaka T, Ohyama T, Iwase K, Ohtani S, Shinoda S, Aono T, Masunaga R, et al.
Endocrinology. 1986 Nov;119(5):2279-83.

Abstract

The effect of calmodulin inhibitors, N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7) and trifluoperazine, on TSH-induced thyroid hormone secretion from rat thyroid was examined in vivo and in vitro. The ip administration of 5 mg W-7 to the rat inhibited T4 and T3 secretion from rat thyroids at 2, 3, and 4 h after the ip injection of 2 IU TSH, and so did the ip injection of trifluoperazine at 3 and 4 h. However, the ip injection of N-(6-aminohexyl)-1-naphthalene sulfonamide as a control substance did not show any significant inhibition of T4 and T3 release. To identify the site of action of calmodulin, the effect of W-7 on (Bu)2cAMP-induced thyroid hormone secretion was tested in vitro. One hundred micromolar W-7 completely inhibited T4 release from the rat thyroid when it was enhanced by TSH or (Bu
Background-Genetic predisposition to life-threatening cardiac arrhythmias such as in congenital long-QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) represent treatable causes of sudden cardiac death in young adults and children. Recently, mutations in calmodulin (CALM1, CALM2) have been associated with severe forms of LQTS and CPVT, with life-threatening arrhythmias occurring very early in life. Additional mutation-positive cases are needed to discern genotype-phenotype correlations associated with calmodulin mutations. Methods and Results-We employed conventional and next-generation sequencing approaches including exome analysis in genotype-negative LQTS probands. We identified five novel de novo missense mutations in CALM2 in three subjects with LQTS (p.N98S, p.N98I, p.D134H) and two subjects with clinical features of both LQTS and CPVT (p.D132E, p.Q136P). Age of onset of major symptoms (syncope or cardiac arrest) ranged from 1-9 years. Three of five ...
The aim of this study was to investigate possible regulation of the hyperpolarization-activated current (I(f)) by cytosolic calcium in guinea-pig sino-atrial (SA) node cells. Isolated SA node cells were superfused with physiological saline solution (36 degrees C) and the perforated patch voltage-clamp technique used to record I(f) activated by hyperpolarizing voltage steps. A 10-min loading of SA node cells with the calcium chelator BAPTA (using 10 microM BAPTA-AM) significantly reduced the amplitude of I(f) at all potentials studied (69+/-8% at -80 mV, n=6). BAPTA loading also shifted the voltage of half-activation (V(h)) of the conductance from -83+/-2 mV in control to -93+/-2 mV in BAPTA (n=6) without significantly altering the slope of activation. The calmodulin antagonists W-7 (10 microM), calmidazolium (25 microM) and ophiobolin A (20 microM) caused similar reductions in I(f) amplitude (73+/-4, 86+/-9 and 59+/-6% at -80 mV, n=6, 5 and 4, respectively) and shifts in V(h) (11+/-3, 14+/-3 and 8+/-2
TY - JOUR. T1 - Expression of the rat calmodulin gene II in the central nervous system. T2 - a 294-base promoter and 68-base leader segment mediates neuron-specific gene expression in transgenic mice. AU - Matsuo, Koichi. AU - Ikeshima, Hiroko. AU - Shimoda, Kouji. AU - Umezawa, Akihiro. AU - Hata, Jun ichi. AU - Maejima, Kazuyoshi. AU - Nojima, Hiroshi. AU - Takano, Toshiya. PY - 1993. Y1 - 1993. N2 - Deletion analysis of the rat CaMII promoter demonstrated that the segment from -294 to +68 bases of CaMII was efficient as a promoter in NIH3T3 by transient assay. We developed transgenic mice carrying a fusion gene of this promoter segment and a β-galactosidase reporter gene. This short CaMII promoter mediated the transgene expression in pyramidal cells of the cerebral neocortex, the pyriformcortex and the hippocampal regions CA1 to CA3, in granule cells of the dentate gyrus, in Purkinje cells of the cerebellum, and in neurons of the lateral vestibular nucleus of pons and the spinal cord of ...
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Calmodulin is an example of a signal-transduction protein. It is a small protein that contains four EF-hand motifs, each of ... Pb2+ (lead) can replace Ca2+ (calcium) as, for example, with calmodulin or Zn2+ (zinc) as with metallocarboxypeptidases[48] ... Chin D, Means AR (August 2000). "Calmodulin: a prototypical calcium sensor". Trends in Cell Biology. 10 (8): 322-8. doi:10.1016 ... Stevens FC (August 1983). "Calmodulin: an introduction". Canadian Journal of Biochemistry and Cell Biology = Revue Canadienne ...
Calmodulin Calmodulin binding molecule 8 Poly-A RNA contating poly (U) sequence ...
The calmodulin antagonist, W7, has also been found to bind to cNTnC to act as a troponin inhibitor. All of these compounds bind ... and calmodulin. In cCTnC the two EF-hand motifs constitute two high affinity Ca2+-binding sites. that are occupied at all ... In a typical EF-hand protein like calmodulin, Ca2+ binding induces a closed-to-open conformational transition, exposing a large ...
Benaim G, Villalobo A (August 2002). "Phosphorylation of calmodulin. Functional implications". European Journal of Biochemistry ...
Application to calmodulin". Biochemistry. 29 (19): 4659-67. doi:10.1021/bi00471a022. PMID 2372549. Lewis E Kay; Mitsuhiko Ikura ...
Benaim G, Villalobo A (August 2002). "Phosphorylation of calmodulin. Functional implications". European Journal of Biochemistry ...
Benaim G, Villalobo A (Aug 2002). "Phosphorylation of calmodulin. Functional implications". European Journal of Biochemistry / ...
Application to calmodulin". Biochemistry. 29 (19): 4659-67. doi:10.1021/bi00471a022. PMID 2372549. Lewis E Kay; Mitsuhiko Ikura ...
Cook WJ, Walter LJ, Walter MR (1995). "Drug binding by calmodulin: crystal structure of a calmodulin-trifluoperazine complex". ... 1993). "Cytosolic domain of the human immunodeficiency virus envelope glycoproteins binds to calmodulin and inhibits calmodulin ... "Functional analysis of the promoters of the human CaMIII calmodulin gene and of the intronless gene coding for a calmodulin- ... Calmodulin 3 is a protein that in humans is encoded by the CALM3 gene. Human CALM3 genome location and CALM3 gene details page ...
This domain binds calmodulin, a protein known as a calcium sensor that can bind and regulate many target proteins. A GRD ( ... Hart MJ, Callow MG, Souza B, Polakis P (Aug 1996). "IQGAP1, a calmodulin-binding protein with a rasGAP-related domain, is a ... Li Z, Sacks DB (February 2003). "Elucidation of the interaction of calmodulin with the IQ motifs of IQGAP1". J. Biol. Chem. 278 ... Li Z, Kim SH, Higgins JM, Brenner MB, Sacks DB (December 1999). "IQGAP1 and calmodulin modulate E-cadherin function". J. Biol. ...
calmodulin binding. • protein binding. Cellular component. • cytoplasm. • cell projection. • membrane. • postsynaptic density. ... Identification of phosphorylation sites and regulation by calmodulin". The Journal of Biological Chemistry. 266 (16): 10544-51 ... Gamby C, Waage MC, Allen RG, Baizer L (Oct 1996). "Analysis of the role of calmodulin binding and sequestration in neuromodulin ... In the case of neuromodulin, it was shown to bind calmodulin avidly. ...
For this reason protein kinases are named based on what regulates their activity (i.e. Calmodulin-dependent protein kinases). ... The 1970s included the discovery of calmodulin-dependent protein kinases and the finding that proteins can be phosphorylated on ... Activation loop Autophosphorylation Ca2+/calmodulin-dependent protein kinase Cell signaling Cyclin-dependent kinase G protein- ...
Tuberculosis toxin blocking phagosome maturation inhibits a novel Ca2!/calmodulin-PI3K hVPS34 cascade. J. Exp. Med. 198:653-659 ...
They are used in Calmodulin. G. W. Rouse; S. K. Goffredi & R. C. Vrijenhoek (2004). "Osedax: Bone-Eating Marine Worms with ...
... produces Calmodulin inhibitors. Many of the strains of Aspergillus stromatoides have been isolated in ... "Calmodulin inhibitors from Aspergillus stromatoides". Chemistry & biodiversity. 10 (3): 328-37. doi:10.1002/cbdv.201200321. ...
"New nuclear functions for calmodulin". Cell Calcium. 23 (2-3): 115-21. doi:10.1016/S0143-4160(98)90109-9. PMID 9601606. ...
One such example is calmodulin. One molecule of calmodulin binds four calcium ions cooperatively. Its structure presents four ... DAPK and EGFR calmodulin binding domains interact with different calmodulin-calcium complexes". Biochimica et Biophysica Acta ( ... "Three-dimensional structure of calmodulin". Nature. 315 (6014): 37-40. doi:10.1038/315037a0. PMID 3990807. Ptashne, M.; Jeffrey ... "A general strategy to characterize calmodulin-calcium complexes involved in CaM-target recognition: ...
Joyal JL, Burks DJ, Pons S, Matter WF, Vlahos CJ, White MF, Sacks DB (November 1997). "Calmodulin activates ...
Ca2+-bound calmodulin (CaM) interacts with Cav1.3 to induce calcium-dependent inactivation (CDI). Recently, it has been shown ... but weakens the pre-binding of Ca2+-free calmodulin (apoCaM) to channels. The upshot is that CDI is continuously tuneable by ... "Calcium calmodulin and hormone secretion". Clinical Endocrinology. 23 (2): 201-18. doi:10.1111/j.1365-2265.1985.tb00216.x. PMID ...
Li Z, Kim SH, Higgins JM, Brenner MB, Sacks DB (December 1999). "IQGAP1 and calmodulin modulate E-cadherin function". The ...
The distinguishing feature of PDE1 as a family is their regulation by calcium (Ca2+) and calmodulin (CaM). Calmodulin has been ... either at the level of calmodulin binding sites such as compound KS505a or directly on Ca2+/calmodulin such as bepril, ... In PDE1 this region contains a calmodulin binding domain. The catalytic domains of PDE1 (and other types of PDEs) have three ... Vinpocetine was described as a specific inhibitor of basal and calmodulin-activated PDE1. This effect leads to an increase of ...
Bähler M, Rhoads A (Feb 2002). "Calmodulin signaling via the IQ motif". FEBS Letters. 513 (1): 107-13. doi:10.1016/S0014-5793( ... Mar 2009). "NuMA-related LIN-5, ASPM-1, calmodulin and dynein promote meiotic spindle rotation independently of cortical LIN-5/ ... where it regulates spindle organization and rotation by interacting with calmodulin, dynein and NuMA-related LIN-5. A new ...
"Cytosolic domain of the human immunodeficiency virus envelope glycoproteins binds to calmodulin and inhibits calmodulin- ... Calmodulin 2 is a protein that in humans is encoded by the CALM2 gene. Mutations in CALM2 are associated to cardiac arrhythmias ... Pan Z, Radding W, Zhou T, Hunter E, Mountz J, McDonald JM (1996). "Role of calmodulin in HIV-potentiated Fas-mediated apoptosis ... Berchtold MW, Egli R, Rhyner JA, Hameister H, Strehler EE (May 1993). "Localization of the human bona fide calmodulin genes ...
Daube H, Billich A, Mann K, Schramm HJ (1991). "Cleavage of phosphorylase kinase and calcium-free calmodulin by HIV-1 protease ... the delta subunit is calmodulin (CALM1; MIM 114180). PHKA2 (MIM 306000) encodes the alpha subunit of liver-specific ...
2006). "Influence of calcium on the proteolytic degradation of the calmodulin-like skin protein (calmodulin-like protein 5) in ... Calmodulin-like protein 5 is a protein that in humans is encoded by the CALML5 gene. This gene encodes a novel calcium binding ... "Entrez Gene: CALML5 calmodulin-like 5". Human CALML5 genome location and CALML5 gene details page in the UCSC Genome Browser. ... Méhul B, Bernard D, Schmidt R (2001). "Calmodulin-like skin protein: a new marker of keratinocyte differentiation". J. Invest. ...
The CaMPDE isoenzymes of 60 kDa from brain, heart and lung are regulated by calmodulin, but the affinities for calmodulin are ... The bovine lung CaMPDE isoenzyme contains calmodulin as a tightly bound subunit, so that a change in calmodulin concentration ... Characterization of calmodulin-dependent cyclic nucleotide phosphodiesterase isoenzymes. R K Sharma, J Kalra ... Calmodulin-dependent phosphodiesterase (CaMPDE) is one of the key enzymes involved in the complex interactions which occur ...
Trifluoperazine (50 microM), a specific inhibitor of calmodulin, inhibited the Ca2+-calmodulin activation of the adenylate ... Differential effects of Ca2+-calmodulin on adenylate cyclase activity cyclase activity in mouse and rat pancreatic islets. P ... Ca2+ (10 microM)-calmodulin (1 microM) stimulated adenylate cyclase activity 53.1 +/- 5.2 (N = 6)% in the particulate fraction ... The results question the role of calmodulin in the Ca2+-dependent rise in cyclic AMP evoked by glucose in pancreatic islets. ...
The NH2-terminal IQ motif bound calmodulin in the absence of free Ca2+, whereas the COOH-terminal IQ motif bound calmodulin in ... The Ca(2+)-binding protein calmodulin was demonstrated to be associated with myr 4. Calmodulin binding activity of myr 4 was ... A further Ca(2+)-dependent calmodulin binding site was mapped to amino acids 776-874 in the myr 4 tail domain. These results ... Rat myr 4 defines a novel subclass of myosin I: identification, distribution, localization, and mapping of calmodulin-binding ...
Mutational analysis of Ca2+-independent autophosphorylation of calcium/calmodulin-dependent protein kinase II. In: Journal of ... Mukherji S, Soderling T. Mutational analysis of Ca2+-independent autophosphorylation of calcium/calmodulin-dependent protein ... Previous studies with synthetic peptides indicate that residues 290-309, corresponding to the calmodulin (CaM)-binding domain ... Mutational analysis of Ca2+-independent autophosphorylation of calcium/calmodulin-dependent protein kinase II. / Mukherji, ...
One of the peptides, whose phosphorylation was inhibited in the presence of excess calmodulin, appeared to be the same as P2. ... One of the peptides, whose phosphorylation was inhibited in the presence of excess calmodulin, appeared to be the same as P2. ... One of the peptides, whose phosphorylation was inhibited in the presence of excess calmodulin, appeared to be the same as P2. ... One of the peptides, whose phosphorylation was inhibited in the presence of excess calmodulin, appeared to be the same as P2. ...
Calmodulin is a small thermostable protein which has been involved in the regulation of a number of cellular activities such as ... Calmodulin is a small thermostable protein which has been involved in the regulation of a number of cellular activities such as ... Calmodulin is apparently present in all nucleated cells. High concentrations from 1-50μM have been reported from a variety of ... Vandermeers A., Vandermeers-Piret MC., Christophe J. (1982) Calmodulin. In: Swillens S., Dumont J.E. (eds) Cell Regulation by ...
... Christine Hughes hughe014 at mc.duke.edu Sat Mar 4 13:09:33 EST 1995 *Previous message: ...
calmodulin-2. Names. Calmodulin-1. Calmodulin-3. LP7057 protein. calmodulin 2 (phosphorylase kinase, delta). phosphorylase ... Calmodulin and calmodulin-dependent protein kinase-II (CaMK-II)-activated p38 MAPK play a role in extracellular Tat-induced IL- ... Calmodulin binds to both HIV-1 Gag and Matrix proteins through an extended calmodulin-binding domain in Matrix (amino acids 11- ... Calmodulin induced events, organism-specific biosystemOne important physiological role for Calmodulin is the regulation of ...
Calmodulin 1 (CALM1) Calmodulin 2 (CALM2) Calmodulin 3 (CALM3) calmodulin 1 pseudogene 1 (CALM1P1) Calmodulin-like 3 (CALML3) ... Calmodulin-like 4 (CALML4) Calmodulin-like 5 (CALML5) Calmodulin-like 6 (CALML6) Calmodulin belongs to one of the two main ... Troponin C, like Calmodulin, has two globular domains that are connected by a linker region. However, Troponin C and Calmodulin ... Calmodulin can also make use of the calcium stores in the endoplasmic reticulum, and the sarcoplasmic reticulum. Calmodulin can ...
1986) Effect of Calmodulin Inhibitors on Thyroid Hormone Secretion. In: Medeiros-Neto G., Gaitan E. (eds) Frontiers in ... Myosin Light Chain Kinase Thyroid Lobe Calmodulin Inhibitor Thyroid Hormone Secretion Thyroid Hormone Release These keywords ... Chlorpromazine inhibits the action of calmodulin which is contained in the thyroid and may act on tubulin assembly-disassembly ... 3). These findings led us to postulate that calmodulin plays a role in TSH-induced thyroid hormone secretion. ...
Calmodulin methyltransferase is an evolutionarily conserved enzyme that trimethylates Lys-115 in calmodulin.. Magnani R, Dirk ... Calmodulin N-methyltransferase. Partial purification and characterization.. Rowe PM, Wright LS, Siegel FL.. J. Biol. Chem. 261 ... Literature: Calmodulin-lysine N-methyltransferase (IPR025800). References used in this entry. The following publications were ...
Calcium-Calmodulin-Dependent Protein Kinase Type 2 delta Subunit. *Calcium Calmodulin Dependent Protein Kinase Type 2 delta ... Calcium-Calmodulin-Dependent Protein Kinase Type 2 alpha Subunit. *Calcium Calmodulin Dependent Protein Kinase Type 2 alpha ... Calcium-Calmodulin-Dependent Protein Kinase Type 2 beta Subunit. *Calcium Calmodulin Dependent Protein Kinase Type 2 beta ... Calcium-Calmodulin-Dependent Protein Kinase Type 2 gamma Subunit. *Calcium Calmodulin Dependent Protein Kinase Type 2 gamma ...
calmodulin-1. Names. Calmodulin 1 (phosphorylase kinase, delta). caM. calmodulin I. NP_114175.1. *EC 2.7.11.19 ... Calmodulin induced events, organism-specific biosystem (from REACTOME) Calmodulin induced events, organism-specific biosystem ... Title: Pivoting between calmodulin lobes triggered by calcium in the Kv7.2/calmodulin complex. ... Calm1 calmodulin 1 [Rattus norvegicus] Calm1 calmodulin 1 [Rattus norvegicus]. Gene ID:24242 ...
Calmodulin 1 is a protein that in humans is encoded by the CALM1 gene. Calmodulin 1 is the archetype of the family of calcium- ... Calmodulin contains 148 amino acids and has 4 calcium-binding EF hand motifs. Its functions include roles in growth and the ... "Entrez Gene: CALM1 calmodulin 1 (phosphorylase kinase, delta)". Takahashi M, Yamagiwa A, Nishimura T, Mukai H, Ono Y (Sep 2002 ... Calmodulin 1 has been shown to interact with: AKAP9, Androgen receptor, IQGAP1, PPEF1, and TRPV1. GRCh38: Ensembl release 89: ...
Calmodulin-kinases: modulators of neuronal development and plasticity.. Wayman GA1, Lee YS, Tokumitsu H, Silva AJ, Soderling TR ... calmodulin and subsequently by protein phosphorylation. One member of this family, CaMKII, is well-established for its effects ...
Other names in common use include ubiquityl-calmodulin synthase, ubiquitin-calmodulin synthetase, ubiquityl-calmodulin ... n-calmodulin The 3 substrates of this enzyme are ATP, calmodulin, and ubiquitin, whereas its 3 products are AMP, diphosphate, ... "Multiple ubiquitination of vertebrate calmodulin by reticulocyte lysate and inhibition of calmodulin conjugation by ... In enzymology, an ubiquitin-calmodulin ligase (EC 6.3.2.21) is an enzyme that catalyzes the chemical reaction n ATP + ...
In molecular biology, calmodulin binding domain (CaMBD) is a protein domain found in small-conductance calcium-activated ... They are heteromeric complexes that comprise pore-forming alpha-subunits and the Ca2+-binding protein calmodulin (CaM). CaM ... "Structure of the gating domain of a Ca2+-activated K+ channel complexed with Ca2+/calmodulin". Nature. 410 (6832): 1120-4. doi: ...
Calmodulin-binding proteins are, as their name implies, proteins which bind calmodulin. Examples include: Gap-43 protein ( ... presynaptic) Neurogranin (postsynaptic) Caldesmon Calmodulin-Binding Proteins at the US National Library of Medicine Medical ...
The multifunctional Ca2+/calmodulin-dependent protein kinases.. Schulman H1.. Author information. 1. Department of Pharmacology ... Multifunctional Ca2+/calmodulin-dependent (CaM) kinase, CaM kinase Ia, CaM kinase Ib and CaM kinase IV are four of the kinases ...
Calcium-dependent folding Calmodulin Calumenin EF-hand Calcium signaling SR-CD SEC-MALS SEC-SAXS SPR ... Zhang M, Abrams C, Wang L et al (2012) Structural basis for calmodulin as a dynamic calcium sensor. Structure 20:911-923 ... Iida S, Potter JD (1986) Calcium binding to calmodulin. Cooperativity of the calcium-binding sites. J Biochem 99:1765-1772 ... 2019) Calcium-Induced Protein Folding in Calumenin and Calmodulin. In: Heizmann C. (eds) Calcium-Binding Proteins of the EF- ...
Studies in a variety of model systems are beginning to identify components of the calcium/calmodulin cascade required for ... Calcium and its ubiquitous intracellular receptor calmodulin are required for cell proliferation. ... Two calcium/calmodulin-dependent enzymes, the multifunctional calcium/calmodulin-dependent protein kinase and the protein ... Studies in a variety of model systems are beginning to identify components of the calcium/calmodulin cascade required for ...
The crystal structure of calcium-calmodulin (CaM) reveals a protein with a typical dumbbell structure. Various spectroscopic ... Bending of the calmodulin central helix: a theoretical study.. *van der Spoel D ... The crystal structure of calcium-calmodulin (CaM) reveals a protein with a typical dumbbell structure. Various spectroscopic ...
The IQ calmodulin-binding motif is an amino acid sequence motif containing the following sequence: [FILV]Qxxx[RK]Gxxx[RK]xx[ ... Rhoads AR, Friedberg F (April 1997). "Sequence motifs for calmodulin recognition". FASEB J. 11 (5): 331-40. PMID 9141499. Xie X ... Calmodulin (CaM) is recognized as a major calcium (Ca2+) sensor and orchestrator of regulatory events through its interaction ...
In molecular biology, the plant calmodulin-binding domain is a protein domain found repeated in a number of plant calmodulin- ... These domains are thought to constitute the calmodulin-binding domains of these proteins. Binding of the proteins to calmodulin ... Reddy VS, Ali GS, Reddy AS (May 2003). "Characterization of a pathogen-induced calmodulin-binding protein: mapping of four Ca2+ ... "Isolation and characterization of a novel calmodulin-binding protein from potato". J. Biol. Chem. 277 (6): 4206-14. doi:10.1074 ...
... calmodulin N6-methyl-L-lysine Thus, the two substrates of this enzyme are S-adenosyl methionine and calmodulin L-lysine, ... In enzymology, a calmodulin-lysine N-methyltransferase (EC 2.1.1.60) is an enzyme that catalyzes the chemical reaction S- ... The systematic name of this enzyme class is S-adenosyl-L-methionine:calmodulin-L-lysine N6-methyltransferase. Other names in ... Sitaramayya A, Wright LS, Siegel FL (1980). "Enzymatic methylation of calmodulin in rat brain cytosol". J. Biol. Chem. 255 (18 ...
  • Rat myr 4 defines a novel subclass of myosin I: identification, distribution, localization, and mapping of calmodulin-binding sites with differential calcium sensitivity. (rupress.org)
  • These results demonstrate a differential Ca2+ sensitivity for calmodulin binding by IQ motifs, and they suggest that myr 4 activity might be regulated by Ca2+/calmodulin. (rupress.org)
  • Several infants with severe forms of long-QT syndrome (LQTS) who displayed life-threatening ventricular arrhythmias together with delayed neurodevelopment and epilepsy were found to have mutations in either this gene or another member of the calmodulin gene family (PMID:23388215). (nih.gov)
  • Mutations in this gene have also been identified in patients with less severe forms of LQTS (PMID:24917665), while mutations in another calmodulin gene family member have been associated with catecholaminergic polymorphic ventricular tachycardia (CPVT)(PMID:23040497), a rare disorder thought to be the cause of a significant fraction of sudden cardiac deaths in young individuals. (nih.gov)
  • Synthetic peptide conjugated to KLH derived from within residues 100 to the C-terminus of Human Calmodulin. (abcam.com)
  • Professor Matthias Rief and colleagues at the Technische Universitaet Muenchen had previously shown that they could fix a single calmodulin molecule between a surface and the cantilever tip of a specially built atomic-force microscope, expose it to calcium ions in solution, induce peptide binding and unbinding, and measure changes in the molecule's mechanical properties as it did its work. (innovations-report.com)
  • By applying mechanical force," Junker says, "we are able to dismantle the calmodulin-target peptide complex with surgical precision. (innovations-report.com)
  • Synthetic peptide corresponding to Human Calmodulin. (abcam.com)
  • Synthetic peptide corresponding to Human Calmodulin 1/2/3 aa 10-30 (C terminal) conjugated to keyhole limpet haemocyanin. (abcam.com)
  • This work describes the development of a new platform for allosteric protein engineering that takes advantage of the ability of calmodulin to change conformation upon binding to peptide and protein ligands. (harvard.edu)
  • A synthesized peptide derived from human Calmodulin, corresponding to a region within the internal amino acids. (thermofisher.com)
  • Here, we report the sequential backbone and side chain resonance assignment of the Ca 2+ -Calmodulin/Munc13-1 458-492 peptide complex at pH 6.8 and 35°C (BMRB No. 15470). (springer.com)
  • Calmodulin participates as a subunit of the channel itself, bound to the cytoplasmic C-terminus region of the peptide called the calmodulin binding domain (CaMBD). (wikipedia.org)
  • GAP43 is also referred to as: protein F1 neuromodulin neural phosphoprotein B-50 axonal membrane protein GAP-43 calmodulin-binding protein P-57 nerve growth-related peptide GAP43 neuron growth-associated protein 43 GAP43, is a nervous tissue-specific cytoplasmic protein that can be attached to the membrane via a dual palmitoylation sequence on cysteines 3 and 4. (wikipedia.org)
  • In enzymology, an ubiquitin-calmodulin ligase (EC 6.3.2.21) is an enzyme that catalyzes the chemical reaction n ATP + calmodulin + n ubiquitin ⇌ {\displaystyle \rightleftharpoons } n AMP + n diphosphate + (ubiquitin)n-calmodulin The 3 substrates of this enzyme are ATP, calmodulin, and ubiquitin, whereas its 3 products are AMP, diphosphate, and (ubiquitin)n-calmodulin. (wikipedia.org)
  • The systematic name of this enzyme class is calmodulin:ubiquitin ligase (AMP-forming). (wikipedia.org)
  • In enzymology, a calmodulin-lysine N-methyltransferase (EC 2.1.1.60) is an enzyme that catalyzes the chemical reaction S-adenosyl-L-methionine + calmodulin L-lysine ⇌ {\displaystyle \rightleftharpoons } S-adenosyl-L-homocysteine + calmodulin N6-methyl-L-lysine Thus, the two substrates of this enzyme are S-adenosyl methionine and calmodulin L-lysine, whereas its two products are S-adenosylhomocysteine and calmodulin N6-methyl-L-lysine. (wikipedia.org)
  • The systematic name of this enzyme class is S-adenosyl-L-methionine:calmodulin-L-lysine N6-methyltransferase. (wikipedia.org)
  • Calmodulin methyltransferase is an evolutionarily conserved enzyme that trimethylates Lys-115 in calmodulin. (ebi.ac.uk)
  • As greater amounts of calcium and calmodulin accumulate, autophosphorylation occurs leading to persistent activation of the CaMKII enzyme for a short period of time. (wikipedia.org)
  • The binding of enzymes may be enhanced if the enzyme substrate is present and enzyme-substrate-calmodulin-Ca 2+ complexes are particularly stable. (sigmaaldrich.com)
  • A truncation which deletes the calmodulin-like domain, as in mutant delta C-6H, disrupts Ca2+ activation and leaves the enzyme with a basal level of activity. (nih.gov)
  • Activation and autophosphorylation of all four enzymes were stringently dependent on Ca2+/calmodulin, indicating that neither Arg-283 nor Thr-286 is an absolute requirement for the pseudosubstrate inhibition of the enzyme. (pnas.org)
  • Activation of the enzyme is ligand-dependent-peptides with higher affinities for wild-type calmodulin exhibit increased switch activity. (harvard.edu)
  • However, calmodulin must remain bound to the enzyme for its activity to be sustained. (wikipedia.org)
  • Here, we describe protocols for the expression and purification of calumenin and calmodulin, another EF-hand protein modulated by calcium, along with protocols for biophysical techniques used to characterize calcium-induced changes to protein conformation. (springer.com)
  • Calmodulin is a small thermostable protein which has been involved in the regulation of a number of cellular activities such as cyclic nucleotide and glycogen metabolism, smooth muscle contraction, intracellular motility, and calcium transport. (springer.com)
  • In this system, we investigate the hitherto unknown physiological roles of calmodulin (CaM) in light adaptation and in regulation of the inward current that is brought about by depletion of cellular Ca 2+ stores. (pnas.org)
  • Craig, T.A., Watterson, D.M., and Hinrichsen, R.D., 1987a, Analysis of a mutant Paramecium with a non-lethal selective alteration in calmodulin regulation and a defective calcium-dependent potassium conductance. (springer.com)
  • Our present understanding implicates both calmodulin (CaM) and 3',5'-cyclicAMP (cAMP) in the regulation of pollen tube growth. (nih.gov)
  • THE small calcium sensor protein calmodulin (CaM) is one of the major mediators of the complex interactions that underlie calcium regulation (see V an E ldik and W atterson 1998 for review). (genetics.org)
  • Data suggest that Cys3602 in RyR2 (ryanodine receptor 2 (show RYR2 Antibodies )) plays important role in activation/termination of Ca2 (show CA2 Antibodies )+ release, but it is not essential for calmodulin regulation of RyR2 (show RYR2 Antibodies ). (antibodies-online.com)
  • Contribution of the KCa3.1 channel-calmodulin interactions to the regulation of the KCa3.1 gating process. (abcam.com)
  • Studies have found that calmodulin participates in the regulation of several biological processes including energy and biosynthetic metabolism, cell motility, exocytosis, cytoskeletal assembly, and intracellular modulation of both cAMP and calcium concentrations. (thermofisher.com)
  • Modular architecture of Munc13/calmodulin complexes: dual regulation by Ca2+ and possible function in short-term synaptic plasticity. (nih.gov)
  • Because of in vitro regulation by Ca2+/calmodulin, PDE1s are believed to function as a mechanism for integrating cell signalling pathways mediated by cGMP and cAMP with pathways that regulate intracellular calcium levels. (wikipedia.org)
  • Chlorpromazine inhibits the action of calmodulin which is contained in the thyroid and may act on tubulin assembly-disassembly (3). (springer.com)
  • N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide, a calmodulin antagonist, inhibits cell proliferation. (springer.com)
  • In this approach, calmodulin acts as the input domain, whose ligand-dependent conformational changes control the activity of the β-lactamase output domain. (harvard.edu)
  • Upon binding to Ca2+, this motif may undergo conformational changes that enable Ca2+-regulated functions as seen in Ca2+ effectors such as calmodulin (CaM) and troponin C (TnC) and Ca2+ buffers such as calreticulin and calbindin D9k. (wikipedia.org)
  • For example, calmodulin binds both NMDA receptors and potassium channels which differ in length by about 50 amino acid residues. (wikipedia.org)
  • Here we show that calmodulin is a critical Ca2+ sensor for both inactivation and facilitation, and that the nature of the modulatory effect depends on residues within the IQ motif important for calmodulin binding. (nih.gov)
  • The phenylalanine residues of calmodulin were implicated in function both by structural studies of calmodulin bound to target peptides and by their extraordinary conservation in evolution. (genetics.org)
  • These results suggest that the several phenylalanine residues in calmodulin are required to different extents in different combinations in order to carry out each of the several essential tasks. (genetics.org)
  • The association of calcium-bound calmodulin (CaM ) with DREAM is mediated by a short amphipathic amino acid sequence located between residues 29 and 44 on DREAM. (antibodies-online.com)
  • Upon complexation, increased amide exchange rates are observed for residues Lys 75 through Thr 79 located in the 'central helix' of calmodulin, and for the C-terminal residues Ser 147 and Lys 148 . (springer.com)
  • Residues Lys 75 -Asp 80 have J H N H α values in the 6-7 Hz range, suggesting that a break in the 'central helix' occurs at the same position as previously observed in solution NMR studies of Ca 2+ -ligated calmodulin. (springer.com)
  • In the case of neuromodulin, it was shown to bind calmodulin avidly. (wikipedia.org)
  • The cDNA encoding A. oryzae calmodulin was expressed under the control of the GAL1 promoter in the calmodulin null mutant (cmd1) of yeast, Saccharomyces cerevisiae, and could function as a calmodulin gene. (nih.gov)
  • In molecular biology, calmodulin binding domain (CaMBD) is a protein domain found in small-conductance calcium-activated potassium channels (SK channels). (wikipedia.org)
  • Molecular analysis of human and rat calmodulin complementary DNA clones. (wikipedia.org)
  • Formation of the autophagic tubes is mediated through Atg7-dependent ubiquitin-like conjugation (Ublc) or via vacuolar transporter chaperone (VTC) molecular complex which acts through calmodulin-dependent manner. (wikipedia.org)
  • A cDNA and genomic gene encoding calmodulin were isolated from Aspergillus oryzae using a part of the calmodulin gene from A. nidulans as a hybridization probe. (nih.gov)
  • An adenylyl cyclase cDNA clone (type II) was isolated from a rat brain library and found to encode a protein of 1090 amino acids that was homologous to but distinct from the previously described Ca2+/calmodulin-stimulated adenylyl cyclase from bovine brain. (pnas.org)
  • Expression of the type II cDNA in an insect cell line resulted in an increased level of adenylyl cyclase activity that was insensitive to Ca2+/calmodulin. (pnas.org)
  • So we can directly observe how the calmodulin snatches the amino acid chain and folds itself, to hold its target fast. (innovations-report.com)
  • Measuring the force needed to bend the calmodulin molecule out of its stable condition at any given moment enables the researchers to compute the energies associated with binding both the calcium ions and the amino acid chains. (innovations-report.com)
  • Although the nucleotide sequence homology with that of A. nidulans was not so high (68%), the deduced amino acid sequence was 100% and 84% identical with calmodulin of A. nidulans and chicken, respectively. (nih.gov)
  • 2-chloro-(epsilon-amino-Lys(75))-[6-4-(N,N'-diethylaminophenyl)-1,3,5-triazin-4-yl]-calmodulin (TA-CaM) and fluorescein-calmodulin (FL-CaM), fluorescent analogues of CaM, were loaded into pollen tubes and CaM activity was mapped by fluorescence ratio imaging. (nih.gov)
  • Calmodulin contains 149 amino acids and has 4 calcium-binding domains. (acris-antibodies.com)
  • A novel calmodulin-binding protein, belonging to the WD-repeat family, is localized in dendrites of a subset of CNS neurons. (wikigenes.org)
  • Activity-dependent modulation of endocytosis by calmodulin at a large central synapse. (nih.gov)
  • In this study, we identified a novel calcium-dependent interaction between EP24.15 and calmodulin, which is important for the stimulated, but not constitutive, secretion of EP24.15. (nih.gov)
  • Using mass spectrometry this study identified calmodulin as a calcium-dependent GluN2A (show GRIN2A Antibodies ) binding partner. (antibodies-online.com)
  • The compounds of the second group, which are reported to inhibit calmodulin dependent events and the increase in cytosolic Ca 2+ (Ca i ) induced by high K + depolarization, were the most efficient inhibitors of [ 3 H]GABA release. (springer.com)
  • Ca2+-bound calmodulin (CaM) interacts with Cav1.3 to induce calcium-dependent inactivation (CDI). (wikipedia.org)
  • Calcium-binding protein 1 which is a neuron -specific member of the calmodulin (CaM) superfamily which modulates Ca2+-dependent activity of inositol trisphosphate receptors (InsP3RS). (wikipedia.org)
  • The activity of eEF-2K is dependent on calcium and calmodulin. (wikipedia.org)
  • The function is conserved, the C. elegans protein ASPM-1 was shown to be localized to spindle asters, where it regulates spindle organization and rotation by interacting with calmodulin, dynein and NuMA-related LIN-5. (wikipedia.org)
  • These results indicate that the same calmodulin molecule may act as a Ca2+ sensor for both positive and negative modulation. (nih.gov)
  • Methods developed by biophysicists at the Technische Universitaet Muenchen (TUM) have enabled them to manipulate and observe calmodulin in action, on the single-molecule scale. (innovations-report.com)
  • Original paper: "Single-molecule force spectroscopy distinguishes target binding modes of calmodulin," by Jan Philipp Junker and Matthias Rief, published in the online Early Edition of PNAS, Proceedings of the National Academy of Sciences for the week of August 10, 2009. (innovations-report.com)
  • We show that calmodulin (CaM), a molecule involved in mediating Ca2+ signalling, is expressed at higher levels in the long and pointed beaks of cactus finches than in more robust beak types of other species. (nih.gov)
  • ala changes to mutant phenotypes support the idea of internal functional redundancy in the symmetrical calmodulin protein molecule. (genetics.org)
  • Thermodynamics of calmodulin binding to cardiac and skeletal muscle ryanodine receptor ion channels. (nih.gov)
  • The skeletal muscle (RyR1) and cardiac muscle (RyR2) ryanodine receptor calcium release channels contain a single, conserved calmodulin (CaM) binding domain, yet are differentially regulated by CaM. (nih.gov)
  • In addition to this in vivo observation, we showed in vitro that the mutant protein is susceptible to a proteolytic activity induced by nitrogen starvation that hardly affects the wild-type calmodulin. (pnas.org)