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.Kinetics: The rate dynamics in chemical or physical systems.Desulfovibrio gigas: A species of gram-negative, anaerobic, spiral-shaped bacteria originally isolated from a saltwater pond in France. It contains a well-characterized metabolic pathway that enables it to survive transient contacts with OXYGEN.Phenylhydrazines: Diazo derivatives of aniline, used as a reagent for sugars, ketones, and aldehydes. (Dorland, 28th ed)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.Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2.Potassium Cyanide: A highly poisonous compound that is an inhibitor of many metabolic processes, but has been shown to be an especially potent inhibitor of heme enzymes and hemeproteins. It is used in many industrial processes.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.Trypsinogen: The inactive proenzyme of trypsin secreted by the pancreas, activated in the duodenum via cleavage by enteropeptidase. (Stedman, 25th ed)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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.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.Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.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.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.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.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.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.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).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.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Enzyme Precursors: Physiologically inactive substances that can be converted to active enzymes.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Type C Phospholipases: A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.DiglyceridesMagnesium: A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Macromolecular Substances: Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.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.Nitric Oxide Synthase: An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Muscles: Contractile tissue that produces movement in animals.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Molecular Weight: The sum of the weight of all the atoms in a molecule.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.

A kinetic study of ribulose bisphosphate carboxylase from the photosynthetic bacterium Rhodospirillum rubrum. (1/44858)

The activation kinetics of purified Rhodospirillum rubrum ribulose bisphosphate carboxylase were analysed. The equilibrium constant for activation by CO(2) was 600 micron and that for activation by Mg2+ was 90 micron, and the second-order activation constant for the reaction of CO(2) with inactive enzyme (k+1) was 0.25 X 10(-3)min-1 . micron-1. The latter value was considerably lower than the k+1 for higher-plant enzyme (7 X 10(-3)-10 X 10(-3)min-1 . micron-1). 6-Phosphogluconate had little effect on the active enzyme, and increased the extent of activation of inactive enzyme. Ribulose bisphosphate also increased the extent of activation and did not inhibit the rate of activation. This effect might have been mediated through a reaction product, 2-phosphoglycolic acid, which also stimulated the extent of activation of the enzyme. The active enzyme had a Km (CO2) of 300 micron-CO2, a Km (ribulose bisphosphate) of 11--18 micron-ribulose bisphosphate and a Vmax. of up to 3 mumol/min per mg of protein. These data are discussed in relation to the proposed model for activation and catalysis of ribulose bisphosphate carboxylase.  (+info)

Nitric oxide stimulates the stress-activated protein kinase p38 in rat renal mesangial cells. (2/44858)

Nitric oxide (NO) has gained increased attention as a diffusible universal messenger that plays a crucial role in the pathogenesis of inflammatory and autoimmune diseases. Recently, we reported that exogenous NO is able to activate the stress-activated protein kinase (SAPK) cascade in mesangial cells. Here, we demonstrate that exposure of glomerular mesangial cells to compounds releasing NO, including spermine-NO and (Z)-1- (N-methyl-N-[6-(N-methylammoniohexyl)amino]diazen)-1-ium-1,2-diolate (MAHMA-NO), results in an activation of the stress-activated p38-mitogen-activated protein kinase (p38-MAPK) cascade as measured by the phosphorylation of the activator of transcription factor-2 (ATF2) in an immunocomplex kinase assay. Activation of the p38-MAPK cascade by a short stimulation (10 min) with the NO donor MAHMA-NO causes a large increase in ATF2 phosphorylation that is several times greater than that observed after stimulation with interleukin-1beta, a well-known activator of the p38-MAPK pathway. Time course studies reveal that MAHMA-NO causes rapid and maximal activation of p38-MAPK after 10 min of stimulation and that activation declines to basal levels within 60 min. The longer-lived NO donor spermine-NO causes a comparable rapid activation of the p38-MAPK pathway; however, the increased activation state of p38-MAPK was maintained for several hours before control values were reattained after 24 h of stimulation. Furthermore, the NO donors also activated the classical extracellular signal-regulated kinase (ERK) p44-MAPK cascade as shown by phosphorylation of the specific substrate cytosolic phospholipase A2 in an immunocomplex kinase reaction. Both MAHMA-NO and spermine-NO cause a rapid activation of p44-MAPK after 10 min of stimulation. Interestingly, there is a second delayed peak of p44-MAPK activation after 4-24 h of stimulation with NO donors. These results suggest that there is a differential activation pattern for stress-activated and mitogen-activated protein kinases by NO and that the integration of these signals may lead to specific cell responses.  (+info)

A Drosophila TNF-receptor-associated factor (TRAF) binds the ste20 kinase Misshapen and activates Jun kinase. (3/44858)

Two families of protein kinases that are closely related to Ste20 in their kinase domain have been identified - the p21-activated protein kinase (Pak) and SPS1 families [1-3]. In contrast to Pak family members, SPS1 family members do not bind and are not activated by GTP-bound p21Rac and Cdc42. We recently placed a member of the SPS1 family, called Misshapen (Msn), genetically upstream of the c-Jun amino-terminal (JNK) mitogen-activated protein (MAP) kinase module in Drosophila [4]. The failure to activate JNK in Drosophila leads to embryonic lethality due to the failure of these embryos to stimulate dorsal closure [5-8]. Msn probably functions as a MAP kinase kinase kinase kinase in Drosophila, activating the JNK pathway via an, as yet, undefined MAP kinase kinase kinase. We have identified a Drosophila TNF-receptor-associated factor, DTRAF1, by screening for Msn-interacting proteins using the yeast two-hybrid system. In contrast to the mammalian TRAFs that have been shown to activate JNK, DTRAF1 lacks an amino-terminal 'Ring-finger' domain, and overexpression of a truncated DTRAF1, consisting of only its TRAF domain, activates JNK. We also identified another DTRAF, DTRAF2, that contains an amino-terminal Ring-finger domain. Msn specifically binds the TRAF domain of DTRAF1 but not that of DTRAF2. In Drosophila, DTRAF1 is thus a good candidate for an upstream molecule that regulates the JNK pathway by interacting with, and activating, Msn. Consistent with this idea, expression of a dominant-negative Msn mutant protein blocks the activation of JNK by DTRAF1. Furthermore, coexpression of Msn with DTRAF1 leads to the synergistic activation of JNK. We have extended some of these observations to the mammalian homolog of Msn, Nck-interacting kinase (NIK), suggesting that TRAFs also play a critical role in regulating Ste20 kinases in mammals.  (+info)

Intracellular signalling: PDK1--a kinase at the hub of things. (4/44858)

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

Bcl-2 regulates amplification of caspase activation by cytochrome c. (5/44858)

Caspases, a family of specific proteases, have central roles in apoptosis [1]. Caspase activation in response to diverse apoptotic stimuli involves the relocalisation of cytochrome c from mitochondria to the cytoplasm where it stimulates the proteolytic processing of caspase precursors. Cytochrome c release is controlled by members of the Bcl-2 family of apoptosis regulators [2] [3]. The anti-apoptotic members Bcl-2 and Bcl-xL may also control caspase activation independently of cytochrome c relocalisation or may inhibit a positive feedback mechanism [4] [5] [6] [7]. Here, we investigate the role of Bcl-2 family proteins in the regulation of caspase activation using a model cell-free system. We found that Bcl-2 and Bcl-xL set a threshold in the amount of cytochrome c required to activate caspases, even in soluble extracts lacking mitochondria. Addition of dATP (which stimulates the procaspase-processing factor Apaf-1 [8] [9]) overcame inhibition of caspase activation by Bcl-2, but did not prevent the control of cytochrome c release from mitochondria by Bcl-2. Cytochrome c release was accelerated by active caspase-3 and this positive feedback was negatively regulated by Bcl-2. These results provide evidence for a mechanism to amplify caspase activation that is suppressed at several distinct steps by Bcl-2, even after cytochrome c is released from mitochondria.  (+info)

Concomitant activation of pathways downstream of Grb2 and PI 3-kinase is required for MET-mediated metastasis. (6/44858)

The Met tyrosine kinase - the HGF receptor - induces cell transformation and metastasis when constitutively activated. Met signaling is mediated by phosphorylation of two carboxy-terminal tyrosines which act as docking sites for a number of SH2-containing molecules. These include Grb2 and p85 which couple the receptor, respectively, with Ras and PI 3-kinase. We previously showed that a Met mutant designed to obtain preferential coupling with Grb2 (Met2xGrb2) is permissive for motility, increases transformation, but - surprisingly - is impaired in causing invasion and metastasis. In this work we used Met mutants optimized for binding either p85 alone (Met2xPI3K) or p85 and Grb2 (MetPI3K/Grb2) to evaluate the relative importance of Ras and PI 3-kinase as downstream effectors of Met. Met2xPI3K was competent in eliciting motility, but not transformation, invasion, or metastasis. Conversely, MetP13K/Grb2 induced motility, transformation, invasion and metastasis as efficiently as wild type Met. Furthermore, the expression of constitutively active PI 3-kinase in cells transformed by the Met2xGrb2 mutant, fully rescued their ability to invade and metastasize. These data point to a central role for PI 3-kinase in Met-mediated invasiveness, and indicate that simultaneous activation of Ras and PI 3-kinase is required to unleash the Met metastatic potential.  (+info)

Activation of c-Abl tyrosine kinase requires caspase activation and is not involved in JNK/SAPK activation during apoptosis of human monocytic leukemia U937 cells. (7/44858)

Genotoxic stress triggers the activation of several sensor molecules, such as p53, JNK1/SAPK and c-Abl, and occasionally promotes the cells to apoptosis. We previously reported that JNK1/SAPK regulates genotoxic stress-induced apoptosis in p53-negative U937 cells by activating caspases. c-Abl is expected to act upstream of JNK1/SAPK activation upon treatment with genotoxic stressors, but its involvement in apoptosis development is still unclear. We herein investigated the kinase activities of c-Abl and JNK1/SAPK during apoptosis elicited by genotoxic anticancer drugs and tumor necrosis factor (TNF) in U937 cells and their apoptosis-resistant variant UK711 cells. We found that the activation of JNK1/SAPK and c-Abl correlated well with apoptosis development in these cell lines. Unexpectedly, however, the JNK1/SAPK activation preceded the c-Abl activation. Moreover, the caspase inhibitor Z-Asp suppressed c-Abl activation and the onset of apoptosis but not the JNK1/SAPK activation. Interestingly, c-Abl tyrosine kinase inhibition by CGP 57148 reduced apoptosis without interfering with JNK1/SAPK activation. These results indicate that c-Abl acts not upstream of JNK1/ SAPK but downstream of caspases during the development of p53-independent apoptosis and is possibly involved in accelerating execution of the cell death pathway.  (+info)

Activation of telomerase and its association with G1-phase of the cell cycle during UVB-induced skin tumorigenesis in SKH-1 hairless mouse. (8/44858)

Telomerase is a ribonucleoprotein enzyme that adds hexanucleotide repeats TTAGGG to the ends of chromosomes. Telomerase activation is known to play a crucial role in cell-immortalization and carcinogenesis. Telomerase is shown to have a correlation with cell cycle progression, which is controlled by the regulation of cyclins, cyclin dependent kinases (cdks) and cyclin dependent kinase inhibitors (cdkis). Abnormal expression of these regulatory molecules may cause alterations in cell cycle with uncontrolled cell growth, a universal feature of neoplasia. Skin cancer is the most prevalent form of cancer in humans and the solar UV radiation is its major cause. Here, we investigated modulation in telomerase activity and protein expression of cell cycle regulatory molecules during the development of UVB-induced tumors in SKH-1 hairless mice. The mice were exposed to 180 mjoules/cm2 UVB radiation, thrice weekly for 24 weeks. The animals were sacrificed at 4 week intervals and the studies were performed in epidermis. Telomerase activity was barely detectable in the epidermis of non-irradiated mouse. UVB exposure resulted in a progressive increase in telomerase activity starting from the 4th week of exposure. The increased telomerase activity either persisted or further increased with the increased exposure. In papillomas and carcinomas the enzyme activity was comparable and was 45-fold higher than in the epidermis of control mice. Western blot analysis showed an upregulation in the protein expression of cyclin D1 and cyclin E and their regulatory subunits cdk4 and cdk2 during the course of UVB exposure and in papillomas and carcinomas. The protein expression of cdk6 and ckis viz. p16/Ink4A, p21/Waf1 and p27/Kip1 did not show any significant change in UVB exposed skin, but significant upregulation was observed both in papillomas and carcinomas. The results suggest that telomerase activation may be involved in UVB-induced tumorigenesis in mouse skin and that increased telomerase activity may be associated with G1 phase of the cell cycle.  (+info)

Trouvez tous les livres de Stenmark, Harald (ed.) - Phosphoinositides in Subcellular Targeting and Enzyme Activation. Sur eurolivre.fr,vous pouvez commander des livres anciens et neufs.COMPARER ET acheter IMMÉDIATEMENT au meilleur prix. 9783540009504
Brajendra K. Tripathi, View ORCID ProfileTiera Grant, Xiaolan Qian, Ming Zhou, Philipp Mertins, Dunrui Wang, Alex G. Papageorge, View ORCID ProfileSergey G. Tarasov, View ORCID ProfileKent W. Hunter, Steven A. Carr, View ORCID ProfileDouglas R. Lowy ...
Rabbit polyclonal BCKDH kinase antibody validated for WB, IHC and tested in Human and Mouse. Referenced in 1 publication. Immunogen corresponding to…
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Elevated levels of the sIL-6R have been associated with the pathology of several disease states. This implies that production of the sIL-6R is increased as part of the inflammatory response. However, little is known regarding the factors that might regulate sIL-6R generation. In this study, physiological concentrations of native CRP and biologically relevant CRP-derived peptides were found to stimulate sIL-6R production by human neutrophils. Release of this soluble receptor was rapidly induced after CRP treatment and occurred via shedding of the cognate IL-6R from the cell surface. C-reactive protein represents the first known endogenous activator of this process. The observation that release of sIL-6R is only partially prevented by the hydroxamic acid-based metalloprotease inhibitor TAPI is of particular interest, since IL-6R shedding in response to phorbol esters and ionomycin has been shown to be prevented by this agent ((12), (20)). Thus, in neutrophils, shedding of the IL-6R presumably ...
Absence of adequate regulation is a prerequisite for pathophysiological developments, like hypersensitivity reactions and cancer. Thus, comprehension of physiological reactions requires knowledge about their regulation. In previous years, we were able to work out the central role which is played by the inositol-5-phosphatase, SHIP1, in regulating appropriate mast cell (MC) responses. If SHIP1 is missing, MCs severely hyper-react in response to diverse stimuli, like allergens, growth factors, and bacterial constituents. So far, this cellular behavior was explained mainly by SHIP1s catalytic function. However, in addition to its catalytic domain SHIP1 possesses various structural possibilities to interact with other proteins (i. e. an adaptor function). To understand how SHIP1 is controlling the physiological activation of MCs and why SHIP1 deficiency is resulting in hyperreactivity of MCs, we will, in this proposed project, thoroughly analyze the structural characteristics of SHIP1 and correlate ...
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Activation results during learning (Day 1).A: JULIDE results. At Day 1, the hippocampus (HP) and the parietal associative cortex (PTLp) are the most activated r
Protein kinase C regulates the activity of a diverse group of cellular proteins including membrane ion channel proteins. Although protein kinase C and its substrate protein have been identified in both membrane and cytosolic fractions in the heart, the physiological role of this kinase in the regulation of cardiac function remains unknown. We examined the physiological role of protein kinase C by stimulating its activity with 12-deoxyphorbol 13 isobutyrate 20 acetate (DPBA) in human trabeculae carneae. This resulted in decreased peak isometric twitch force and peak intracellular sarcoplasmic reticulum calcium release as detected with aequorin. Furthermore, in the presence of DPBA, steady-state force-[Ca2+] relations were shifted to higher intracellular calcium concentrations, and the Hill coefficient was reduced, indicating a decrease in responsiveness of the myofilaments to calcium and a change in cooperativity among thin filament proteins, respectively. Thus, DPBA affects not only ...
Stress-activated protein kinases (SAPKs) are stimulated by cell damaging agents as well as by physiological receptor agonists. In this study we show that human platelets contain the isoforms SAPK2a, SAPK2b, SAPK3 and SAPK4 as determined by immunoblotting with specific antibodies. All four kinases were activated in thrombin-stimulated platelets whereas only SAPK2a and SAPK2b were significantly stimulated by collagen. All four isoforms were able to phosphorylate wild-type human cPLA2in vitro, although to different extents, but not cPLA2 mutants that had Ser505 replaced by alanine. Phosphorylation at Ser505 was confirmed by phosphopeptide mapping using microbore HPLC. SAPK2a and 42-kDa mitogen-activated protein kinase incorporated similar levels of phosphate into cPLA2 relative to the ability of each kinase to stimulate phosphorylation of myelin basic protein. SAPK2b and SAPK4 incorporated less phosphate, and cPLA2 was a poor substrate for SAPK3. The inhibitor of SAPK2a and SAPK2b, SB 202190, ...
Maudsley S., Pierce K.L., Zamah A.M., Miller W.E., Ahn S., Daaka Y., Lefkowitz R.J., Luttrell L.M.. Many G protein-coupled receptors (GPCRs) activate MAP kinases by stimulating tyrosine kinase signaling cascades. In some systems, GPCRs stimulate tyrosine phosphorylation by inducing the "transactivation" of a receptor tyrosine kinase (RTK). The mechanisms underlying GPCR-induced RTK transactivation have not been clearly defined. Here we report that GPCR activation mimics growth factor-mediated stimulation of the epidermal growth factor receptor (EGFR) with respect to many facets of RTK function. beta(2)-Adrenergic receptor (beta(2)AR) stimulation of COS-7 cells induces EGFR dimerization, tyrosine autophosphorylation, and EGFR internalization. Coincident with EGFR transactivation, isoproterenol exposure induces the formation of a multireceptor complex containing both the beta(2)AR and the "transactivated" EGFR. beta(2)AR-mediated EGFR phosphorylation and subsequent beta(2)AR stimulation of ...
One of the key mediators of the antiviral and antiproliferative actions of interferon is double-stranded-RNA-dependent protein kinase (PKR). PKR activity is also involved in the regulation of cell proliferation, apoptosis and signal transduction. We have recently identified PACT, a novel protein activator of PKR, as an important modulator of PKR activity in cells in the absence of viral infection. PACT heterodimerizes with PKR and activates it by direct protein-protein interactions. Endogenous PACT acts as an activator of PKR in response to diverse stress signals, such as serum starvation and peroxide or arsenite treatment, and is therefore a novel, stress-modulated physiological activator of PKR. In this study, we have characterized the functional domains of PACT that are required for PKR activation. Our results have shown that, unlike the N-terminal conserved domains 1 and 2, the third conserved domain of PACT is dispensable for its binding of double-stranded RNA and inter action with PKR. ...
The data reported herein show the capacity of NSC 651016 to act as an inhibitor of CXCL12-mediated angiogenesis in a variety of in vitro and in vivo angiogenesis assays. Furthermore, these data suggest the potential application of NSC 651016 as an antiangiogenic therapy because it blocked endothelial cell migration, capillary-like tube formation, and angiogenesis. Furthermore, NSC 651016 may have wider applications in cancer therapy. CXCL12 has been implicated in the proliferation of astrocytes (14) by activating extracellular signal-regulated kinase 1/2 but not p38 or stress-activated protein kinase/c-Jun NH2-terminal kinase pathways (14) , therefore, CXCL12 may have a direct role in pathological glial cell proliferation such as reactive gliosis and brain tumor formation. Thus, blockade of CXCL12 function by NSC 651016 may have direct therapeutic benefits for certain brain cancers, one of the most refractory tumor types known. Additionally, CXCL12 participates in cancer cell metastasis by ...
p,This chapter presents a general approach for the application of spatial intensity distribution analysis (SpIDA) to the pharmacodynamic quantification of receptor tyrosine kinase homodimerization in response to direct ligand activation or transactivation by G-protein-coupled receptors. Intensity histograms are generated from single fluorescence microscopy images. These histograms are then fit with Poissonian distributions to obtain density maps and quantal brightness values of the labeled proteins underlying the images. This approach allows resolving monomer/oligomer protein mixtures within subcellular compartments using conventional confocal laser scanning microscopy. The application of quantitative pharmacological analysis to data obtained using SpIDA provides a universal method for comparing studies between cell lines and receptor systems. In contrast to methods based on resonance energy transfer, SpIDA is suitable not only for use in recombinant systems but also for the characterization of ...
Concepts regarding the controls and consequences of PKD1-Ser738/Ser742 (activation loop) phosphorylation are based largely on early studies that used an anti-PKD1-Ser(P)738/Ser(P)742 PSSA (from Cell Signaling Technology, Danvers, MA) and showed that PMA increases PKD1 activation loop phosphorylation in many cell types via a mechanism that requires nPKC isoform activity (PKCδ, PKCε, PKCη, and/or PKCθ). In vitro kinase assays showing direct phosphorylation of the PKD1 activation loop by certain nPKC isoforms also have been published (Brändlin et al., 2002). However, there is recent evidence that the Cell Signaling Technology anti-PKD1-Ser(P)738/Ser(P)742 PSSA primarily recognizes PKD1 phosphorylation at Ser738 and that PKD1 phosphorylation at Ser742 can be tracked with a different PSSA (commercially available from Abcam Inc., Cambridge, MA). Experiments that use a combined approach with these two PSSAs expose differences in the controls and consequences of PKD1 phosphorylation at Ser738 and ...
Sprouty-related, EVH1 domain-containing protein 3 also known as Spread-3 is a protein that in humans is encoded by the SPRED3 gene. Spread-3 is a member of the Sprouty (see SPRY1/SPRED) family of proteins that regulate growth factor-induced activation of the MAP kinase cascade. GRCh38: Ensembl release 89: ENSG00000188766 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000037239 - Ensembl, May 2017 "Human PubMed Reference:". "Mouse PubMed Reference:". "Entrez Gene: sprouty-related". Nonami A, Kato R, Taniguchi K, Yoshiga D, Taketomi T, Fukuyama S, Harada M, Sasaki A, Yoshimura A (December 2004). "Spred-1 negatively regulates interleukin-3-mediated ERK/mitogen-activated protein (MAP) kinase activation in hematopoietic cells". The Journal of Biological Chemistry. 279 (50): 52543-51. doi:10.1074/jbc.M405189200. PMID 15465815. Kato R, Nonami A, Taketomi T, Wakioka T, Kuroiwa A, Matsuda Y, Yoshimura A (March 2003). "Molecular cloning of mammalian Spred-3 which suppresses tyrosine ...
Glycerol kinase antibody [N1N3-2] (glycerol kinase) for ICC/IF, WB. Anti-Glycerol kinase pAb (GTX107474) is tested in Human samples. 100% Ab-Assurance.
Many stimuli mediate activation and nuclear translocation of ERK (extracellular-signal-regulated kinase) by phosphorylation on the TEY (Thr-Glu-Tyr) motif. This is necessary to initiate transcriptional programmes controlling cellular responses, but the mechanisms that govern ERK nuclear targeting are unclear. Single-cell imaging approaches have done much to increase our understanding of input-output relationships in the ERK cascade, but few studies have addressed how the range of ERK phosphorylation responses observed in cell populations influences subcellular localization. Using automated microscopy to explore ERK regulation in single adherent cells, we find that nuclear localization responses increase in proportion to stimulus level, but not the level of TEY phosphorylation. This phosphorylation-unattributable nuclear localization response occurs in the presence of tyrosine phosphatase and protein synthesis inhibitors. It is also seen with a catalytically inactive ERK2-GFP (green fluorescent ...
It has been suggested that S100A8 acts as an endogenous activator of the immune response (6). S100A8 expression is strongly upregulated in various inflammatory diseases, such as sepsis, rheumatoid arthritis, inflammatory bowel disease, vasculitis, and cancer (5). NAFLD has been increasingly recognized as an inflammatory disease as well as a metabolic disease (4). However, the involvement of S100A8 in the pathogenesis of NAFLD remains unclear. In the current study, we demonstrated that S100A8 expression was remarkably increased in the livers of HFHCD-fed mice that developed steatohepatitis. We also demonstrated that S100A8 protein was significantly more expressed in the liver tissues of patients with NASH than in those of patients with NAFL. These results suggested that S100A8 was associated with the development of NAFLD. Furthermore, we demonstrated that S100A8 was primarily produced in the myeloid lineage cell population, CD11b+Gr-1high cells in the liver leukocytes of both ND- and HFHCD-fed ...
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Separation of the catalytic and stimulatory regulatory subunits of rat brain adenylate cyclase.: The catalytic subunit of rat brain adenylate cyclase was separa
Sigma-Aldrich offers abstracts and full-text articles by [Shinichi Meguro, Noriko Osaki, Koji Onizawa, Noriyuki Yajima, Tadashi Hase, Noboru Matsuo, Ichiro Tokimitsu].
TA Sciences is creating research-based clinically tested wellness supplements that help address cellular aging through the science of Telomerase Activation.
In pyroptosis experiments, nigericin can be used as a positive control to generate a robust caspase-1 activation response in a variety of cell lines.
To demon selleckchem strate irrespective of whether ET 1 stimulates ERK1 two, p38 MAPK, and JNK1 2 phosphorylation via a G protein coupled ETB re ceptor cascade, pretreatment with BQ 788, GPA2, or GPA2A attenuated ET 1 stimulated ERK1 2, p38 MAPK, and JNK1 two phosphorylation through the period of observation. These results demonstrated that G protein coupled ETB dependent activation of ERK1 2, p38 MAPK, and JNK1 2 by ET 1 is, at the least in part, needed for COX two expression in bEnd. 3 cells. NFB is required for ET 1 induced COX two expression ET 1 has been shown to modulate cellular functions via activation of NFB signaling in a variety of cell sorts. To examine no matter whether activation of NFB is essential for ET 1 induced COX 2 expression, as shown in Figure 5A and B, pretreatment with a selective NFB inhibitor Bay11 7082, which blocks activation of NFB signaling, attenuated ET 1 induced COX 2 protein and mRNA expression in bEnd. three cells. To figure out whether or not the involvement ...
Phorbol ester-sensitive EL4 murine thymoma cells respond to phorbol 12-myristate 13-acetate with activation of ERK mitogen-activated protein kinases, synthesis of interleukin-2, and death, whereas phorbol ester-resistant variants of this cell line do not exhibit these responses. Additional aspects of the resistant phenotype were examined, using a newly-established resistant cell line. Phorbol ester induced morphological changes, ERK activation, calcium-dependent activation of the c-Jun N-terminal kinase (JNK), interleukin-2 synthesis, and growth inhibition in sensitive but not resistant cells. A series of protein kinase C activators caused membrane translocation of protein kinase Cs (PKCs) alpha, eta, and theta in both cell lines. While PKC eta was expressed at higher levels in sensitive than in resistant cells, overexpression of PKC eta did not restore phorbol ester-induced ERK activation to resistant cells. In sensitive cells, PKC activators had similar effects on cell viability and ERK ...
Cancer cells have different characteristics due to the genetic differences where these unique features may strongly influence the effectiveness of therapeutic interventions. Here, we show that the spontaneous reactivation of extracellular signal-regulated kinase (ERK), distinct from conventional ERK activation, represents a potent mechanism for cancer cell survival. We studied ERK1/2 activation in vitro in SW480 colorectal cancer cells. Although ERK signaling tends to be transiently activated, we observed the delayed reactivation of ERK1/2 in epidermal growth factor (EGF)-stimulated SW480 cells. This effect was observed even after EGF withdrawal. While phosphorylated ERK1/2 translocated into the nucleus following its primary activation, it remained in the cytoplasm during late-phase activation. The inhibition of primary ERK1/2 activation or protein trafficking, blocked reactivation and concurrently increased caspase 3 activity. Our results suggest that the biphasic activation of ERK1/2 plays a ...
G-protein-coupled receptor agonists are powerful stimulators of mitogen-activated protein kinase (MAPK) cascades in cardiac myocytes. However, little is known regarding the physiological activation of enzymes downstream of MAPKs. We examined the activation of mitogen- and stress-activated protein kinase-1 (MSK1), a downstream target of MAPKs, in adult rat cardiac myocytes by phenylephrine and endothelin-1. Both agonists induced the phosphorylation of MSK1 at Thr-581 and Ser-376 but not at Ser-360. Maximal phosphorylation was observed at 10-15min after stimulation and it correlated with increased activity. Maximal activation of MSK1 in adult cardiomyocytes temporally coincided with maximal p38 MAPK activation while activation of the extracellular-signal-regulated kinase (ERK) cascade was more rapid. Phosphorylation and activation of MSK1 was completely inhibited by either PD98059 (ERK1/2 pathway inhibitor) or SB203580 (p38 MAPK inhibitor) alone. These data demonstrate that MSK1 activation in ...
Phagocyte superoxide production by a multicomponent NADPH oxidase is important in host defense against microbial invasion. However inappropriate NADPH oxidase activation causes inflammation. Endothelial cells express NADPH oxidase and endothelial oxidative stress due to prolonged NADPH oxidase activation predisposes many diseases. Discovering the mechanism of NADPH oxidase activation is essential for developing novel treatment of these diseases. The p47(phox) is a key regulatory subunit of NADPH oxidase; however, due to the lack of full protein structural information, the mechanistic insight of p47(phox) phosphorylation in NADPH oxidase activation remains incomplete. Based on crystal structures of three functional domains, we generated a computational structural model of the full p47(phox) protein. Using a combination of in silico phosphorylation, molecular dynamics simulation and protein/protein docking, we discovered that the C-terminal tail of p47(phox) is critical for stabilizing its ...
H2O2 and oxygen-derived free radicals modulate vasodilator mechanisms.1 2 3 4 5 6 9 The present studies indicate that H2O2 enhances adenylyl cyclase activation and that the effect is dependent (in part) on the presence of iron and is blunted by agents that act to inhibit tyrosine kinase activity.. Our data suggest that the oxygen-derived species mediating the enhancement of adenylyl cyclase activation is either H2O2 itself or the hydroxyl radical. Incubation of cells with xanthine oxidase and purine resulted in a qualitatively similar enhancement of adenylyl cyclase activation. The effect of purine and xanthine oxidase was not blocked by coincubation with superoxide dismutase (which catalyzes the conversion from superoxide anion to H2O2). This suggests that the generation of the superoxide anion is not involved in the mechanism of enhancement of adenylyl cyclase activation. However, pretreatment with either catalase (which catalyzes conversion of H2O2 to water) or with deferoxamine (which ...
TY - JOUR. T1 - Stimulation of Jun N-terminal kinase (JNK) by gonadotropin-releasing hormone in pituitary αt3-1 cell line is mediated by protein kinase C, c-Src, and CDC42. AU - Levi, N. L.. AU - Hanoch, T.. AU - Benard, Outhiriaradjou. AU - Rozenblat, M.. AU - Harris, D.. AU - Reiss, N.. AU - Naor, Z.. AU - Seger, R.. PY - 1998. Y1 - 1998. N2 - The signaling of ligands operating via heterotrimeric G proteins is mediated by a complex network that involves sequential phosphorylation events. Signaling by the G protein-coupled receptor GnRH was shown to include elevation of Ca2+ and activation of phospholipases, protein kinase C (PKC) and extracellular signal-regulated kinase (ERK). In this study, GnRH was shown to activate Jun N-Terminal Kinase (JNK)/SAPK in αT3-1 cells in a PKC- and tyrosine kinase-dependent manner. GnRH as well as tumor-promoting agent (TPA) also increased c-Src activity, which peaked at 2 min after GnRH stimulation and was sensitive both to PKC and to tyrosine kinase ...
Global Markets Directs, Protein Kinase C Epsilon Type (nPKC Epsilon or PRKCE or EC 2.7.11.13) - Pipeline Review, provides in depth analysis on Protein Kinase C Epsilon Type (nPKC Epsilon or PRKCE or EC 2.7.11.13) targeted pipeline therapeutics.
Although accumulating evidence supports that JNK activation is involved in cancer development and progression [37, 38], the biological significance of JNK in gastric cancer remains unclear. The present study showed that constitutive activation of JNK was associated with specific clinicopathological factors, including pTNM stages, lymphatic invasion, and a better prognosis. We believe that this is the first report regarding the clinical implications of JNK in human gastric cancer. Furthermore, we found that JNK negatively regulates FOXO1 activation in gastric cancer cells. This finding contrasts with the results of the previous studies [22, 27-31], which showed JNK-induced activation of FOXO proteins in human cancer cells.. In the present study, JNK activation (evaluated by pJNK staining) was mainly observed in the proliferative zone of the gastric gland and in the areas showing intestinal metaplasia, which is known to be a predictor of gastric neoplasia [39], in the non-neoplastic gastric ...
We found that removal of Ca2+ and inhibition of PKC prevented high Pi-induced O2·− production (Figures 3A and 3B), indicating a role for mechanosensitive Ca2+ signaling and PKC-dependent pathways in high Pi-induced upregulation of NAD(P)H oxidase activity. This idea is consistent with the findings that high Pi elicited significantly greater increases in smooth muscle [Ca2+]i than normal levels of Pi (Figure 4). The important role of Ca2+ signaling is also supported by the finding that administration of a Ca2+ ionophore resulted in significantly increased arterial O2·− production (Figure 3C). Further, pharmacological activation of PKC2 elicited substantial increases in arterial NAD(P)H oxidase-derived O2·− generation (Figure 3C). Because removal of Ca2+ during high-pressure treatment prevented endothelial dysfunction (Figure 1) and increases in O2·− production in high Pi-exposed arteries (Figure 3A) and phorbol ester-stimulated O2·− generation in normotensive arteries could also be ...
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What cellular and molecular properties of neurons in the T-SWR support a 45 min spacing interval for two-trial LTM? Studies of the patterning requirements for the induction of long-term facilitation (LTF) of the tail SN-motor neuron (MN) synapse parallel those for sensitization memory in the T-SWR (Mauelshagen et al., 1996, 1998). For example, four spaced (ISI of 15 min) pulses of exogenous 5-HT are required to induce LTF at tail SN-MN synapses (Mauelshagen et al., 1996). If 5-HT release within the CNS is a critical signaling event initiated by TS, an important experimental question is whether two spaced 5-HT pulses (ISI of 45 min) can induce LTF or whether additional 5-HT signaling (provided by additional pulses) is required.. The analysis of repeated trial learning in Aplysia has identified several critical molecular requirements for LTM induction downstream of 5-HT. These include the signaling kinases protein kinase A (PKA), MAPK, the transcription factor CREB1, and CRE-mediated transcription ...
The soil-dwelling nematode C. elegans is a powerful system for comparative molecular analyses of environmental stress response mechanisms. Infection of worms with bacterial and fungal pathogens causes the activation of well-characterized innate immune transcriptional programs in pathogen-exposed hypodermal and intestinal tissues. However, the pathophysiological events that drive such transcriptional responses are not understood. Here, we show that infection-activated transcriptional responses are, in large part, recapitulated by either physiological or genetic activation of the osmotic stress response. Microarray profiling of wild type worms exposed to non-lethal hypertonicity identified a suite of genes that were also regulated by infection. Expression profiles of five different osmotic stress resistant (osr) mutants under isotonic conditions reiterated the wild type transcriptional response to osmotic stress and also showed substantial similarity to infection-induced gene expression under isotonic
View mouse Mapkapk5 Chr5:121525038-121545905 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
Protein Kinase C Theta Type (nPKC Theta or PRKCQ or EC 2.7.11.13) - Pipeline Review, H1 2017 Size and Share Published in 2017-05-30 Available for US$ 3500 at Researchmoz.us
MAPK3 [ENSP00000263025]. Extracellular signal-regulated kinase 1; Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are ...
Rabbit recombinant monoclonal Myosin light chain kinase antibody [EP1458Y] validated for WB, IHC, Flow Cyt, ICC/IF and tested in Human, Mouse and Rat…
PubMed journal article Inhibition of cyclooxygenase-2-mediated matriptase activation contributes to the suppression of prostate cancer cell motility and metastasi were found in PRIME PubMed. Download Prime PubMed App to iPhone or iPad.
|p|GF 109203X is a potent and selective inhibitor of protein kinase C [1].|/p||p| Protein kinase C (PKC) is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of serine and threon
Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that mediates non-redundant functions in T-cell receptor (TCR) signaling, including T-cells activation, proliferation, differentiation and survival, by mediating activation of multiple transcription factors such as NF-kappa-B, JUN, NFATC1 and NFATC2. In TCR-CD3/CD28-co-stimulated T-cells, is required for the activation of NF-kappa-B and JUN, which in turn are essential for IL2 production, and participates in the calcium-dependent NFATC1 and NFATC2 transactivation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11 on several serine residues, inducing CARD11 association with lipid rafts and recruitment of the BCL10-MALT1 complex, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. May also play an indirect role in activation of the non-canonical NF-kappa-B (NFKB2) pathway. In the signaling pathway leading to
Phosphorylation of mitogen-activated protein kinases (MAPKs) on specific tyrosine and threonine sites by MAP kinase kinases (MAPKKs) is thought to be the sole activation mechanism. Here, we report an unexpected activation mechanism for p38α MAPK that does not involve the prototypic kinase cascade. Rather it depends on interaction of p38α with TAB1 [transforming growth factor-β-activated protein kinase 1 (TAK1)-binding protein 1] leading to autophosphorylation and activation of p38α. We detected formation of a TRAF6-TAB1-p38α complex and showed stimulus-specific TAB1-dependent and TAB1-independent p38α activation. These findings suggest that alternative activation pathways contribute to the biological responses of p38α to various stimuli. ...
RAF activation and inhibition. A promising approach is to target the RAF protein, a crucial intermediary in cell signal transmission. Because of its preponderant role in tumor formation, pharmaceutical companies have invested considerable effort to identify molecules that inhibit RAF enzymatic activity. Although there has been some clinical success, it turns out that on the whole these inhibitors have the unfortunate habit of stimulating the growth of cancer cells instead of reducing it; a paradox that has puzzled an entire community of investigators and clinicians.. IRIC investigators recently discovered new elements to explain this paradox by showing how RAF activation requires three interconnected events involving RAF and RAS and how the drugs currently available unexpectedly stimulate some of those interactions. This new understanding at the molecular level results in being able to propose characteristics that the new generation of RAF inhibitors must possess to constitute effective cancer ...
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This site contains prices and technical information for products manufactured and sold by LC Laboratories. LC Laboratories manufactures laboratory reagents used to study signal transduction processes in cells and tissues in biomedical research. Signal transduction comprises the process by which communications between cells in an organism are transmitted from the outside surface of the cells into internal regions. LC Labs' products, which are the highest quality and lowest priced in the market, are produced either by: 1) isolation and/or semi-synthetic modification of natural products using preparative liquid chromatography (HPLC); or 2) multi-step total synthesis.
I have started measuring in-situ Protein Kinase C activity in permeabilized cells grown in 96-well plates, based on a few references from the literature such as: Heasley L.E., J.Biol.Chem., 1989, 264, 8646. I always get high activity after stimulation with phorbol esters and very low activity after treatment with PKC inhibitors. The problem is that the activity in untreated cells is often almost as high as in stimulated cells. Any advice or protocol would be welcome. Thanks Bernard medbpl at emory.edu ...
Sluyter, R., Shemon, A. & Wiley, J. S. (2007). P2X7 receptor activation causes phosphatidylserine exposure in human erythrocytes. Biochemical and Biophysical Research Communications, 355 169-173 ...
The Ka value of HNO3 is about 24. HNO3 is the chemical formula for strong nitric acid. The Ka value, also known as the acid dissociation equilibrium constant, is a measure of the acidity of a...
It is a member of the 14-3-3 family which consists of 30kDa proteins that are involved in multiple protein kinase signaling pathways, regulation of…
... MAPK 経路 LIMK, subsequent phosphorylation of cofilin, and migration of major human T cells in the three dimen
Obesity is caused by damage to stem cells from aging. This damage is caused at the level of the telomeres and is reversible by telomerase activation
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Browse our collection of workplace homicides information for news stories, slideshows, opinion pieces and related videos posted on AOL.com.
Protein kinases have become central in the efforts to understand the nature of various diseases, and a lot is invested into creating effective therapeutic strategies and finding effective and selective protein kinase inhibitors. In order to succeed it is also important to focus on the structure of the kinases, their exact biological role, and how they interact and cooperate in the signaling. The exact structure of MAPKAPK5 is still unknown, and selective inhibitors are yet to be identified. Even though some of its biological roles are starting to emerge more work is required, including searching for selective inhibitors, analyzing its structure and interactions with its interaction partners. In order to analyze the structure of MAPKAPK5, homology models were generated and their ability to discriminate between binders and non-binders were analyzed. Based on the results, one model was found satisfactory and may be used as a working tool for further experimental studies and possibly structure aided ...
TY - JOUR. T1 - The Mechanism of Heat Shock Activation of ERK Mitogen-activated Protein Kinases in the Interleukin 3-dependent ProB Cell Line BaF3. AU - Ng, D.C.H.. AU - Bogoyevitch, M.A.. PY - 2000. Y1 - 2000. M3 - Article. VL - 275. SP - 40856. EP - 40866. JO - The Journal of Biological Chemistry. JF - The Journal of Biological Chemistry. SN - 0021-9258. IS - 52. ER - ...
As the colonic epithelium is physiologically exposed to butyrate and to activators of protein kinase C, we examined the effect of the protein kinase C signalling pathway on butyrate-induced expression of markers of differentiation. Activators and inhibitors of protein kinase C were used in combination with butyrate and effects on the expression of markers of differentiation examined in colon cancer cell lines. When the protein kinase C activator phorbol myristate acetate (100 nM) was added for 24 h prior to the addition of 2 mM butyrate, there was a synergistic increase in alkaline phosphatase activity (154 ± 11% above that for butyrate alone, P = 0.003) in a concentration- and time-dependent manner. Butyrate-induced expression of carcinoembryonic antigen and interleukin-8, dome formation and cell turnover were also markedly augmented by pre-treatment with phorbol myristate acetate. A similar effect was observed with propionate or acetate (but not other differentiating agents), when phorbol ...
TT-232 is a somatostatin analogue containing a five-residue ring structure. The present report describes TT-232-induced signalling events in A431 cells, where a 4-h preincubation with the peptide irreversibly induced a cell death program, which involves DNA-laddering and the appearance of shrunken nuclei, but is unrelated to somatostatin signalling. Early intracellular signals of TT-232 include a transient two-fold activation of the extracellular signal-regulated kinase (ERK2) and a strong and sustained activation of the stress-activated protein kinases c-Jun NH(2)-terminal kinase (JNK)/SAPK and p38MAPK. Blocking the signalling to ERK or p38MAPK activation had no effect on the TT-232-induced cell killing. At the commitment time for inducing cell death, TT-232 decreased EGFR-tyrosine phosphorylation and prevented epidermial growth factor (EGF)-induced events like cRaf-1 and ERK2 activation. Signalling to ERK activation by FCS, phorbol 12-myristate 13-acetate (PMA) and platelet-derived growth ...
Phosphorylation in the activation segment of protein kinases is a common mechanism of kinase regulation. However, activation loop phosphorylation of many kinases generally induces activating structural changes by repositioning key structural elements that permit substrate and cofactor binding and efficient catalysis (51). Although no common mechanism has been proposed for negative regulation of protein-Ser/Thr kinases, phosphorylation of several of the CDKs within the subdomain I GXGXXG motif at the Thr14 and Tyr15 (human CDK1 numbering) are known to be inhibitory (67-69), and acetylation of the ATP coordinating Lys has been shown to reduce the kinase activity of CDK9 (70).. Here, we establish for the first time that mimicking phosphorylation of PLK1 on Tyr217 in the P+1 loop completely inhibits detectable kinase activity, likely through inhibition of substrate binding, although we cannot formally rule out the possibility that the effect is due to the Glu substitution rather than a ...
Introduction: Cardiac overexpression of muscle specific caveolin-3 (Cav3) protects against ischemic/reperfusion injury through Akt kinase activation. However, the mechanism by which Cav3 regulates Akt activation remains unclear. We tested the hypothesis that Cav3 regulates Akt activity by directly modulating Akt activation loop phosphorylation (T308 in Akt1).. Methods and Results: Adult mouse cardiac myocytes were infected with an adeno-virus that expressed Cav3 and GFP (Ad-GFP/Cav3). In the absence of serum, Cav3 overexpression did not significantly promote T308 phosphorylation. However, when myocytes were stimulated with insulin for 15 minutes, Cav3 synergized with insulin to induce T308 phosphorylation (Ad-GFP-In: 6.9±1.3, Ad-GFP/Cav3-In: 13.7±0.8, p,0.01). The cholesterol-depleting lipid raft inhibitor, cyclodextrin (CyDex), prevented Cav3-mediated Akt activation, suggesting that Cav3 regulates Akt activation through lipid rafts. To test whether lipid rafts directly modulate Akt-T308 ...
Inhibition of MAPKs and activator protein-1. MAPKs have been implicated in many physiologic processes, including cell proliferation, differentiation, and death. There are three major types of MAPKs in mammalian cells, the extracellular signal-regulated protein kinases (ERK), the p38 MAPKs, and the c-Jun NH2-terminal kinases (JNK). The major pathways that lie downstream of the membrane-associated receptor tyrosine kinases (RTK) are shown in Fig. 1. In this cascade, Ras interacts with and activates Raf-1, which in turn phosphorylates and activates MAP/ERK kinase 1/2 (MEK1/2). Activated MEK1/2 then phosphorylates ERK1/2. The JNK1/2/3 and p38α/β/γ pathways are parallel MAPK cascades in mammalian cells. Once activated, MAPKs (ERK, JNK, and p38) activate ELK and c-Jun. Phosphoinositide 3-kinase (PI3K) is activated by RTKs and it synthesizes the second messenger, phosphatidyl inositol-3,4,5-triphosphate, which is necessary for phosphorylation of Akt. Akt directly phosphorylates the proapoptotic ...
PRAK antibody [N3C3] (mitogen-activated protein kinase-activated protein kinase 5) for ICC/IF, WB. Anti-PRAK pAb (GTX107938) is tested in Human samples. 100% Ab-Assurance.
Platelet-derived growth factor (PDGF) is a family of signaling molecules that stimulates cell growth, survival and migration. PDGF is recognized by specific transmembrane proteins, the PDGF receptors, which relay the signals to the cell activating the Mitogen-activated protein (MAP) kinases and other signaling pathways. Aberrant activation of these pathways is frequently detected in cancer. Hence, the study of these processes is essential for identifying potential drug targets or diagnostic markers.. In paper I, we identified Receptor Subfamily 4 Group A Member 1 NR4A1 to be regulated by PDGF via MAP kinases, clarifying the role of Extracellular signal-regulated kinases (Erk) 1/2, Erk5 and Nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) in its regulation. NR4A1 was found to be important for the tumorigenic potential, measured as anchorage-independent growth, of glioblastoma cells.. Since the cellular responses elicited by PDGF result from the balance between phosphorylation ...
Recently, we demonstrated that interaction of multimeric HIV-1 envelope gp120 with the CD4 receptor induces T cell activation, resulting both in NF-κB nuclear translocation and AP-1 activation. Furthermore, analysis of biochemical events generated upon HIV-CD4 interaction was found to activate several cellular kinases, including p56lck, Raf-1, and ERK-2, suggesting a possible involvement of a Raf-1-dependent ERK signaling pathway in this process. The purpose of this study was to investigate the role of MEK and ERK in the signal-transduction pathway(s) leading to AP-1 and NF-κB activation following engagement of CD4 with HIV-1. We demonstrate in this study that both MEK-1 and ERK-1 are dowstream cellular intermediates in this CD4 receptor-dependent activation cascade that are required for efficient activation of the two DNA-binding proteins.. Although the signaling pathway that leads to AP-1 activation following engagement of CD4 with HIV-1 was not known, it is well established that AP-1 ...
Gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus acts upon its receptor in the anterior pituitary to regulate the production and release of the gonadotropins, LH and FSH. The GnRHR is coupled to Gq/11 proteins to activate phospholipase C which transmits its signal to diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG activates the intracellular protein kinase C (PKC) pathway and IP3 stimulates release of intracellular calcium. In addition to the classical Gq/11, coupling of Gs is occasionally observed in a cell-specific fashion. Signaling downstream of protein kinase C (PKC) leads to transactivation of the epidermal growth factor (EGF) receptor and activation of mitogen-activated protein kinases (MAPKs), including extracellular-signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and p38 MAPK. Active MAPKs translocate to the nucleus, resulting in activation of transcription factors and rapid induction of early genes ...
The MAP kinase p38 is activated by noncanonical BMP signaling, and also by cellular stress, with p38 activity providing a second readout of intrinsic and extrinsic function. If Gdf6a promotes apoptosis by increasing cell stress, upregulated p38 activity would be observed in mutants, while the converse would occur if p38 is a mediator of Gdf6a signaling. Compared with gdf6a+/+ siblings (Fig. 4A), gdf6a−/− embryos exhibit markedly increased ocular p38 MAP kinase phosphorylation assessed with whole-mount IHC using phospho-specific (Thr180/Tyr182) p38 MAP kinase antibodies (Fig. 4B). If such increased levels of phosphorylated-p38 MAP kinases activate apoptosis, inhibition of this kinase would be expected to rescue the gdf6a −/− cell death phenotype. To test this, we applied a pharmacologic inhibitor of p38 MAP kinase (SB203580 [60 μM]) to zebrafish embryos and examined apoptosis using caspase-3 IHC. Treatment with SB203580 partially inhibits the increased ocular caspase-3 activation of ...
Upon agonist stimulation, α1B-adrenergic receptors (α1B-ARs) couple to Gq, calcium signaling and protein kinase C activation; subsequently, the receptors are phosphorylated, desensitized and internalized. Internalization seems to involve scaffolding proteins, such as α-arrestin and clathrin. However, the fine mechanisms that participate remain unsolved. The roles of protein kinase C and the small GTPase, Rab9, in α1B-AR vesicular traffic were investigated by studying α1B-adrenergic receptor-Rab protein interactions, using Forster resonance energy transfer (FRET), confocal microscopy, and intracellular calcium quantitation. In HEK293 cells overexpressing DsRed-tagged α1B-ARs and EGFP-tagged Rab proteins, pharmacological protein kinase C activation mimicked α1B-AR traffic elicited by non-related agents, such as sphingosine 1-phosphate, i.e., transient α1B-AR-Rab5 FRET signal followed by a sustained α1B-AR-Rab9 interaction, suggesting brief receptor localization in early endosomes and ...
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First let me go back to my concerns about curcumin. Curcumin is a c-Jun NH(2)-terminal kinase (JNK) inhibitor. [1,2] This thing, a c-Jun NH(2)-terminal kinase (JNK) is also known as a stress-activated protein kinase (SAPK). Even the abbreviation SAPK is a mouthful but anyway, SAPK activation is necessary for cell death in response to exposure to certain forms of stress (including various chemotherapeutic agents) and defects in SAPK signaling promote cell survival. In other words curcumin makes it harder for stress or injury to kill a cell. Generally this is a good thing except when the stress and trauma happen to be chemotherapy which you are giving on purpose to kill cells. The study which started this entire worry showed that in a test tube, breast cancer cells being treated with Adriamycin or Cytoxan were somewhat protected by curcumin.[3 ...
Welcome to Recharge Biomedical, home of Dr. Ed Park and TA-65. Telomerase activation recharges your stem cells making you younger naturally, from the inside out
This collection of references is based on Cardioprotection induced by Na1/K1-ATPase activation involves extracellular signal-regulated kinase 1/2 and phosphoinositide 3-kinase/Akt pathway: Chronic heart failure (CHF) is a common, costly, disabling, and deadly condition in which a problem with the st ... ...
This collection of references is based on Cardioprotection induced by Na1/K1-ATPase activation involves extracellular signal-regulated kinase 1/2 and phosphoinositide 3-kinase/Akt pathway: Chronic heart failure (CHF) is a common, costly, disabling, and deadly condition in which a problem with the st ... ...
Kit Component:- KN206583G1, MAPK11 gRNA vector 1 in pCas-Guide vector- KN206583G2, MAPK11 gRNA vector 2 in pCas-Guide vector- KN206583D, donor vector…
S. Chatterjee, P. Mizar, R. Cassel, R. Neidl, B. R. Selvi, D.V Mohankrishna, B. Vedamurthy, A. Schneider, O. Bousiges, C. Mathis, J.C. Cassel, M. Eswaramoorthy, T. K. Kundu and A. L. Boutillier, A novel activator of CBP/p300 acetyltransferases promotes neurogenesis and extends memory duration in adult mice, J. Neuro Science 33, 10698 - 10712 (2013 ...
Effects of PKC activators on ACh-induced increases in [Ca2+]i. Fura-2 loaded endothelial cells were treated with ACh (3 μmol/L) followed by washing. Cells were
2. Most likely this is the result of a positive feedback mechanism, because if it was negative feedback, the production of the substance would most likely cease when it reaches high concentrations (e.g. d[A]/dt = -k [A]). A positive feedback mechanism, however, requires a brake, which, in this scenario, may not have been present, thus leading to the overproduction of the substance ...
|p| Ro 31-8220 is a selective inhibitor of protein kinase C (PKC) with IC50 values of 5, 24, 14, 27, and 24 nM for PKC α, PKC βI, PKC βII, PKC γ and PKC ε, respectively [1]. |/p| |p| PKC is a monomeric Ca2+- and phospholipid-dependent Ser/Thr protein kin
Background Negatively regulates MAP kinase activation by limiting the formation of Raf/MEK complexes probably by inactivation of the KSR1 scaffold protein. Also acts as a Ras responsive E3 ubiquitin ligase that, on activation...
p38 MAPK inhibitors (inhibiting targets of signaling pathways) used for various assays, some have entered clinical trials, which would be new cancer therapies.
ERK3/4. ERK3 (MAPK6) and ERK4 (MAPK4) are structurally related atypical MAPKs possessing SEG motifs in the activation loop and displaying major differences only in the C-terminal extension. ERK3 and ERK4 are primarily cytoplasmic proteins which bind, translocate and activate MK5 (PRAK, MAPKAP5). ERK3 is unstable, unlike ERK4 which is relatively stable.[12] ...
The mitogen-activated protein kinase-activated protein kinase MK5 is a substrate of the mitogen-activated protein kinases p38, ERK3 and ERK4. Cell culture and animal studies have demonstrated that MK5 is involved in tumour suppression and promotion, embryogenesis, anxiety, cell motility and cell cycle regulation. In the present study, homology models of MK5 were used for molecular dynamics (MD) simulations of: (1) MK5 alone; (2) MK5 in complex with an inhibitor; and (3) MK5 in complex with the interaction partner p38α. The calculations showed that the inhibitor occupied the active site and disrupted the intramolecular network of amino acids. However, intramolecular interactions consistent with an inactive protein kinase fold were not formed. MD with p38α showed that not only the p38 docking region, but also amino acids in the activation segment, αH helix, P-loop, regulatory phosphorylation region and the C-terminal of MK5 may be involved in forming a very stable MK5-p38α complex, and that p38α
TY - JOUR. T1 - Biochemical basis for the functional switch that regulates hepatocyte growth factor receptor tyrosine kinase activation. AU - Sheth, Payal R.. AU - Hays, John L.. AU - Elferink, Lisa. AU - Watowich, Stanley. PY - 2008/4/1. Y1 - 2008/4/1. N2 - Ligand-induced dimerization of receptor tyrosine kinases (RTKs) modulates a system of linked biochemical reactions, sharply switching the RTK from a quiescent state to an active state that becomes phosphorylated and triggers intracellular signaling pathways. To improve our understanding of this molecular switch, we developed a quantitative model for hepatocyte growth factor receptor (c-MET) activation using parameters derived in large part from c-MET kinetic and thermodynamic experiments. Our model accurately produces the qualitative and quantitative dynamic features of c-MET phosphorylation observed in cells following ligand binding, including a rapid transient buildup of phosphorylated c-MET at high ligand concentrations. In addition, our ...
The p38 mitogen-activated protein (MAP) kinase signal transduction pathway is activated by proinflammatory cytokines and environmental stress. The detection of p38 MAP kinase in the nucleus of activated cells suggests that p38 MAP kinase can mediate signaling to the nucleus. To test this hypothesis, we constructed expression vectors for activated MKK3 and MKK6, two MAP kinase kinases that phosphorylate and activate p38 MAP kinase. Expression of activated MKK3 and MKK6 in cultured cells caused a selective increase in p38 MAP kinase activity. Cotransfection experiments demonstrated that p38 MAP kinase activation causes increased reporter gene expression mediated by the transcription factors ATF2 and Elk-1. These data demonstrate that the nucleus is one target of the p38 MAP kinase signal transduction pathway. ...
Complement factor C3, recently found to contain covalently bound phosphate, was phosphorylated in vitro by cyclic AMP-dependent protein kinase (protein kinase A) and Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C). Both protein kinases phosphorylated the same serine residue(s) located in the C3a portion of the alpha-chain. In addition, protein kinase C phosphorylated the beta-chain to a lesser extent. Protein kinase A gave a maximal incorporation of 1 mol of phosphate/mol of C3 while that value with protein kinase C was 1.5 mol of phosphate/mol of C3. The velocity in pmol of [32P]phosphate/(min x unit kinase) was 20 times higher for protein kinase C than for protein kinase A although a 10 times lower ratio of protein kinase to C3 was used in the former case. The apparent Kmfor C3 was 2.6 µM when protein kinase C was used. The phosphorylated C3 was found to be more resistant to partial degradation by trypsin than unphosphorylated C3. It was also found that ...
MAPK8 [ENSP00000378974]. Stress-activated protein kinase JNK1; Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including ...
Delayed cytoprotection (preconditioning) occurs 24h after sublethal simulated ischaemia and reperfusion (SI/R) in neonatal rat ventricular cardiomyocytes. SI/R was used to investigate the role of activation of mitogen-activated protein kinases (MAPKs), stress-activated protein kinases (SAPKs) and phosphoinositide 3-kinase-dependent protein kinase B (PKB)/Akt in cytoprotection. SI resulted in transient dual (Thr/Tyr) phosphorylation of p42/p44-MAPK and p38-MAPK, weak phosphorylation of p46/p54-SAPK, but no phosphorylation of PKB. Reperfusion caused further transient phosphorylation of p38-MAPK, but sustained phosphorylation of p42/p44-MAPK (lasting 4h) and of Ser473 of PKB (lasting 2h). Furthermore, SI/R (24h) induced delayed protection against lethal SI, as determined by an increase in cell viability {bioreduction of MTT [3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide]} and a decrease in cell injury (release of creatine kinase). Both protection and phosphorylation of ...
TY - JOUR. T1 - Multiple forms of brain adenylate cyclase. T2 - Stimulation by Mn2+. AU - Malamuda, Daniel F.. AU - DiRusso, Concetta C.. AU - Aprille, June R.. PY - 1977/11/23. Y1 - 1977/11/23. N2 - Mn2+-stimulated adenylate cyclase (ATP pyrophosphate-lyase-(cyclizing), EC 4.6.1.1) activity in detergent solubilized preparations from mouse brain. While NaF-stimulated activity was decreased by both solubilization and storage at 0-4°C, the ability of the enzyme to be stimulated by Mn2+ was maintained for up to one week. By including Mn+ in the assay of adenylate cyclase in gel fractions after isoelectric focusing, two distinct peaks of enzyme activity (pI1 = 5.8, pI2 = 6.4) were detected, suggesting the existence of more than one type of catalytic subunit in mouse brain cell membranes.. AB - Mn2+-stimulated adenylate cyclase (ATP pyrophosphate-lyase-(cyclizing), EC 4.6.1.1) activity in detergent solubilized preparations from mouse brain. While NaF-stimulated activity was decreased by both ...
MK08_HUMAN] Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In ...
A tetracycline-regulated reporter system was used to investigate the regulation of cyclooxygenase 2 (Cox-2) mRNA stability by the mitogen-activated protein kinase (MAPK) p38 signaling cascade. The stable beta-globin mRNA was rendered unstable by insertion of the 2, 500-nucleotide Cox-2 3 untranslated region (3 UTR). The chimeric transcript was stabilized by a constitutively active form of MAPK kinase 6, an activator of p38. This stabilization was blocked by SB203580, an inhibitor of p38, and by two different dominant negative forms of MAPK-activated protein kinase 2 (MAPKAPK-2), a kinase lying downstream of p38. Constitutively active MAPKAPK-2 was also able to stabilize chimeric beta-globin-Cox-2 transcripts. The MAPKAPK-2 substrate hsp27 may be involved in stabilization, as beta-globin-Cox-2 transcripts were partially stabilized by phosphomimetic mutant forms of hsp27. A short (123-nucleotide) fragment of the Cox-2 3 UTR was necessary and sufficient for the regulation of mRNA stability by the p38
Nitric oxide (NO) is a gaseous compound that serves as a signaling molecule in cellular interactions. In the vasculature, NO is synthesized from endogenous agents by endothelial nitric oxide synthase (eNOS) where it plays key roles in several functions related to homeostasis, adaptation, and development. Recent experimental studies have revealed cycles of increasing and decreasing NO production when eNOS is stimulated by factors such as glucose or insulin. We offer a mathematical model of a generic amino acid receptor site on eNOS wherein this species is subject to activation/deactivation by a pair of interactive kinase and phosphatase species. The enzyme kinetic model is presented as a system of ordinary differential equations including time delay to allow for various intermediate, unspecified complexes. We show that under conditions on the model parameters, varying the delay time may give rise to a Hopf bifurcation. Properties of the bifurcating solutions are explored via a center manifold reduction,
The cell signaling docking protein p130cas became tyrosine-phosphorylated in SH-SY5Y human neuroblastoma cells during induced differentiation with 12-O-tetradecanoylphorbol-13-acetate (TPA) and serum or a combination of basic fibroblast growth factor (bFGF) and insulin-like growth factor-I (IGF-I). The differentiating cells develop a neuronal phenotype with neurites and growth cones and sustained activation of protein kinase C (PKC) and pp60c-src. The TPA-induced p130cas phosphorylation increased within 5 min of stimulation and persisted for at least 4 days, whereas bFGF/IGF-I-induced p130cas phosphorylation was biphasic. However, the increase in tyrosine phosphorylation of p130cas was not restricted to differentiation inducing stimuli. The phosphorylation was blocked by the specific PKC inhibitor GF 109203X, and transient transfection with active PKC-epsilon induced p130cas tyrosine phosphorylation. pp60c-src, known to directly phosphorylate p130cas in other cell systems, was not activated ...
MAP kinase-activated protein kinase 2 (MAPKAPK2) is an enzyme that in humans is encoded by the MAPKAPK2 gene. MAPKAP kinase-2 (MK2) is originally identified by its phosphorylation of glycogen synthase at serine-7 and the corresponding serine in a peptide (GS peptide-1) modelled after the N-terminus of glycogen synthase.. MAPKAP kinase-2 is a novel protein kinase activated by mitogen-activated protein kinase. This MAP kinase activated protein kinase, termed MAPKAP kinase-2, is distinguished from S6 kinase-II (MAPKAP kinase-1) by its response to inhibitors, lack of phosphorylation of S6 peptides and amino acid sequence.. ...
The protein encoded by this gene is a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act in a signaling cascade that regulates various cellular processes such as proliferation, differentiation, and cell cycle progression in response to a variety of extracellular signals. This kinase is activated by upstream kinases, resulting in its translocation to the nucleus where it phosphorylates nuclear targets. Alternatively spliced transcript variants encoding different protein isoforms have been described. [provided by RefSeq, Jul 2008 ...
Extracellular-signal-regulated kinases (ERKs), also called mitogen-activated protein kinases (MAPKs), are widely expressed signaling proteins that regulate meiosis, mitosis, and postmitotic functions in differentiated cells. Following activation by upstream kinases, ERKs are translocated to the nucleus, where they perform their regulatory functions. Disruption of ERK-mediated pathways is common in many cancers. Two members of this family were originally identified with 85% sequence similarity, called ERK1 and ERK2. ERK1 is also known as MAPK3, extracellular signal-regulated kinase 1, insulin-stimulated MAP2 kinase, microtubule-associated protein 2 kinase, PRKM3, ERT2, p44-ERK1, p44-MAPK, HS44KDAP, HUMKER1A, MAP kinase 1, and MAPK1. ERK2 is also known as MAPK1, extracellular signal-regulated kinase 2, PRKM1, PRKM2, ERT1, p41-ERK1, p41-MAPK, p42-MAPK, MAP kinase 1, MAP kinase 2, MAPK1, MAPK2, p38, p40, and p41.. ...
Extracellular-signal-regulated kinases (ERKs), also called mitogen-activated protein kinases (MAPKs), are widely expressed signaling proteins that regulate meiosis, mitosis, and postmitotic functions in differentiated cells. Following activation by upstream kinases, ERKs are translocated to the nucleus, where they perform their regulatory functions. Disruption of ERK-mediated pathways is common in many cancers. Two members of this family were originally identified with 85% sequence similarity, called ERK1 and ERK2. ERK1 is also known as MAPK3, extracellular signal-regulated kinase 1, insulin-stimulated MAP2 kinase, microtubule-associated protein 2 kinase, PRKM3, ERT2, p44-ERK1, p44-MAPK, HS44KDAP, HUMKER1A, MAP kinase 1, and MAPK1. ERK2 is also known as MAPK1, extracellular signal-regulated kinase 2, PRKM1, PRKM2, ERT1, p41-ERK1, p41-MAPK, p42-MAPK, MAP kinase 1, MAP kinase 2, MAPK1, MAPK2, p38, p40, and p41.. ...
MAP kinase-activated protein kinase 2 is an enzyme that in humans is encoded by the MAPKAPK2 gene. This gene encodes a member of the Ser/Thr protein kinase family. This kinase is regulated through direct phosphorylation by p38 MAP kinase. In conjunction with p38 MAP kinase, this kinase is known to be involved in many cellular processes including stress and inflammatory responses, nuclear export, gene expression regulation and cell proliferation. Heat shock protein HSP27 was shown to be one of the substrates of this kinase in vivo. Two transcript variants encoding two different isoforms have been found for this gene. SB 203580, suppresses the activation of MAPKAPK2 MAPKAPK2 has been shown to interact with: AKT1, MAPK14, PHC2, and SHC1. GRCh38: Ensembl release 89: ENSG00000162889 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000016528 - Ensembl, May 2017 "Human PubMed Reference:". "Mouse PubMed Reference:". Zu YL, Wu F, Gilchrist A, Ai Y, Labadia ME, Huang CK (Jun 1994). "The primary ...
article{1b8edece-ac08-4e30-9e8c-455b71ce3ca9, abstract = {The cholinergic regulation of phospholipase D activity was studied in SH-SY5Y human neuroblastoma cells with phosphatidylethanol formation as a specific marker for the enzyme activity. The muscarinic antagonists, hexahydrosiladifenidol and pirenzepine, inhibited carbachol-induced phosphatidylethanol formation in a concentration-dependent manner and the inhibitory constants indicated that muscarinic M1 receptors are responsible for the major part of the phospholipase D activation. The mechanism of receptor-mediated phospholipase D activation varies between different cell types and receptors. In SH-SY5Y cells, the carbachol-induced phospholipase D activity was inhibited by protein kinase C inhibitors. Since both phospholipases D and C are activated by muscarinic stimulation in SH-SY5Y cells, most of the phospholipase D activation is probably secondary to the protein kinase C activation that follows phospholipase C-mediated increase in ...
This gene product is a 626-amino acid polypeptide that is 96.5% identical to mouse Mekk3. Its catalytic domain is closely related to those of several other kinases, including mouse Mekk2, tobacco NPK, and yeast Ste11. Northern blot analysis revealed a 4.6-kb transcript that appears to be ubiquitously expressed. This protein directly regulates the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by activating SEK and MEK1/2 respectively; it does not regulate the p38 pathway. In cotransfection assays, it enhanced transcription from a nuclear factor kappa-B (NFKB)-dependent reporter gene, consistent with a role in the SAPK pathway. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008 ...
Extracellular signal-regulated kinases(ERKs), belonging to the family of mitogen-activated protein kinases (MAPKs), are cytoplasmic and nuclear serine/threonine kinases involved in the signal transduction of several extracellular effectors. Recent evidence indicates the presence of p21 Ras and the phosphorylation of ERK1 and ERK2, suggesting the occurrence of the Ras/ERK cascade in mammalian spermatozoa. The present article describes the biological role of ERK during the acrosome reaction of human spermatozoa on stimulation with zona pellucida (ZP). The mitogen-activated protein-kinase inhibitor PD098059 was used as a pharmacological tool to study the involvement of extracellular signal-regulated kinases in the induction of the acrosome reaction in human spermatozoa. This compound significantly inhibited the acrosome reaction induced by both ZP and the calcium ionophore A23187. These results suggest that ERKs are involved in the signal trans-duction pathway through which ZP stimulation works ...
"Ribonucleotide activation by enzyme ribonucleotide reductase: understanding the role of the enzyme". J Comput Chem. 25 (16): ... The iron-dependent enzyme, ribonucleotide reductase (RNR), is essential for DNA synthesis. Class I RNR enzymes are constructed ... Since the enzyme catalyses the de novo synthesis of deoxyribonucleotides (dNTPs), precursors to DNA synthesis, it is essential ... Organisms are not limited to having one class of enzymes. For example, E. coli have both class I and class III RNR. The ...
Fu PP, Xia Q, Lin G, Chou MW (2004). "Pyrrolizidine alkaloids--genotoxicity, metabolism enzymes, metabolic activation, and ... These tests and similarities in the peptide sequences of the proteins encoded by these genes to known enzymes indicate that one ... Further steps in loline biosynthesis are thought to proceed with sequential PLP-enzyme-catalyzed and oxidative decarboxylations ... coupled in a condensation reaction linking the γ-carbon in homoserine to the secondary amine in proline in a PLP-type enzyme- ...
Direct activation of enzymes by binding calcium is common; some other enzymes are activated by noncovalent association with ... Trypsin, a digestive enzyme, uses the first method; osteocalcin, a bone matrix protein, uses the third. Some other bone matrix ... continuously reformed through neutron activation of natural 40Ca.[24] Many other calcium radioisotopes are known, ranging from ... as cofactors in many enzymes; and in fertilization. Calcium ions outside cells are important for maintaining the potential ...
Desterro JM, Rodriguez MS, Kemp GD, Hay RT (1999). "Identification of the enzyme required for activation of the small ubiquitin ... Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes ... Ubiquitin-conjugating enzyme E2 E3 is a protein that in humans is encoded by the UBE2E3 gene.[5][6] ... ubiquitin conjugating enzyme activity. • ubiquitin-protein transferase activity. • transferase activity. • protein binding. ...
The gab genes upon activation produce enzymes that degrade GABA to succinate. The presence of nitrogen activates the csiR gene ... The enzymes produced by these genes convert GABA to succinate, which then enters the TCA cycle, to be used as a source of ... Joloba, Moses L.; Clemmer, Katy M.; Sledjeski, Darren D.; Rather, Philip N. (2004). "Activation of the gab Operon in an RpoS- ... The gabT gene encodes for GABA transaminase, an enzyme that catalyzes the conversion of GABA and 2-oxoglutarate into succinate ...
Activation of the enzyme leading to H2O2 production. Agmatine sulfate injection can increase food intake with carbohydrate ... Matrix metalloproteases (MMPs). Indirect down-regulation of the enzymes MMP 2 and 9. Advanced glycation end product (AGE) ... "Agmatine enhances the NADPH oxidase activity of neuronal NO synthase and leads to oxidative inactivation of the enzyme". ...
Involvement of serine 54 in the enzyme activation". The Journal of Biological Chemistry. 271 (28): 16526-34. doi:10.1074/jbc. ... cAMP-specific 3',5'-cyclic phosphodiesterase 4D is an enzyme that in humans is encoded by the PDE4D gene. The PDE4D gene is ... Sette C, Conti M (Jul 1996). "Phosphorylation and activation of a cAMP-specific phosphodiesterase by the cAMP-dependent protein ...
PI-3K is composed of a regulatory subunit (P85) and a catalytic subunit (P110). P85 regulates the activation of PI-3K enzyme . ... An example of positive feedback mechanism in the insulin transduction pathway is the activation of some enzymes that inhibit ... Other enzymes will push the pathway forward causing a positive feedback like the AKT and P70 enzymes. When insulin binds to its ... The activation of MAP-Kinase leads to completion of mitogenic functions like cell growth and gene expression. The activation of ...
Calcium overloading can also cause damage by over-activation of calcium-stimulated enzymes. Honokiol can reduce calcium influx ... Additionally, honokiol regulates the nuclear factor kappa B (NF-κB) activation pathway, an upstream effector of vascular ... Honokiol also blocks inflammatory factor production in glial cells through the inhibition on NF-κB activation.[21][22] This ... "Honokiol inhibits the inflammatory reaction during cerebral ischemia reperfusion by suppressing NF-κB activation and cytokine ...
These are produced by intrapancreatic activation of pancreatic enzymes. Lipase activation produces the necrosis of fat tissue ... The activation of these digestive enzymes lead to inflammation, edema, vascular injury, and even cellular death. The death of ... This occurs through inappropriate activation of inactive enzyme precursors called zymogens (or proenzymes) inside the pancreas ... Acute pancreatitis occurs when there is abnormal activation of digestive enzymes within the pancreas. ...
Decker H, Schweikardt T, Nillius D, Salzbrunn U, Jaenicke E, Tuczek F (August 2007). "Similar enzyme activation and catalysis ...
Feedback activation is when the enzyme is activated by a product of degradation of the terminal metabolite. Parallel activation ... Activation through a precursor is defined as when an enzyme is activated by a precursor of its substrate and a particularly ... frequent case of this is activation of the enzyme by the substrate itself. Allosteric enzymes are usually under the ... Since the activation energy of a covalent bond is high the reaction will have a slower speed than that of a non-covalent bond ( ...
Evidence for C-terminal involvement in enzyme activation by lecithin". Arch. Biochem. Biophys. 327 (1): 45-52. doi:10.1006/abbi ... D-beta-hydroxybutyrate dehydrogenase, mitochondrial is an enzyme that in humans is encoded by the BDH1 gene. This gene encodes ... The encoded protein forms a homotetrameric lipid-requiring enzyme of the mitochondrial membrane and has a specific requirement ... 2000). "Phosphatidylcholine activation of human heart (R)-3-hydroxybutyrate dehydrogenase mutants lacking active center ...
... which activates some of the cycle enzymes; and the RuBisCo enzyme activation, active in the Calvin cycle, which involves its ... The enzyme RuBisCo has its own, more complex activation process. It requires that a specific lysine amino acid be carbamylated ... The enzymes in the Calvin cycle are functionally equivalent to most enzymes used in other metabolic pathways such as ... The product of the first step is enediol-enzyme complex that can capture CO 2 or O 2. Thus, enediol-enzyme complex is the real ...
The enzyme pectinase lowers the activation energy needed for the juice to be produced and catalyzes the reaction. ... Pectinase enzymes are used for extracting juice from purée. This is done when the enzyme pectinase breaks down the substrate ... Pectinase is an enzyme that breaks down pectin, a polysaccharide found in plant cell walls. Commonly referred to as pectic ... Therefore, pectinase enzymes are commonly used in processes involving the degradation of plant materials, such as speeding up ...
July 2002). "Enzymes associated with reductive activation and action of nitazoxanide, nitrofurans, and metronidazole in ... enzyme-dependent electron transfer reaction which is essential to anaerobic energy metabolism. It has also been shown to have ...
Direct activation of enzymes by binding calcium is common; some other enzymes are activated by noncovalent association with ... Trypsin, a digestive enzyme, uses the first method; osteocalcin, a bone matrix protein, uses the third. Some other bone matrix ... as cofactors in many enzymes; and in fertilization.[5] Calcium ions outside cells are important for maintaining the potential ... continuously reformed through neutron activation of natural 40Ca.[26] Many other calcium radioisotopes are known, ranging from ...
doi:10.1016/0141-0229(90)90114-6. Que, Jr., Lawrence; Ho, Raymond (1996). "Dioxygen Activation by Enzymes with Mononuclear Non- ... The two enzymes can be distinguished based on their reaction products and cofactors. 1,2-CTD uses Fe3+ as a cofactor to cleave ... The enzyme resembles a boomerang in shape, and can therefore be clearly divided into three domains: two catalytic domains ... Almost all members of the 1,2-CTD family are homodimers; the 1,2-CTD enzyme produced by Pseudomonas arvilla is the exception to ...
"Proteasome recruitment and activation of the Uch37 deubiquitinating enzyme by Adrm1". Nature Cell Biology. 8 (9): 994-1002. doi ... preventing random protein-enzyme encounter and uncontrolled protein degradation. The 19S regulatory particles can recognize ... "hRpn13/ADRM1/GP110 is a novel proteasome subunit that binds the deubiquitinating enzyme, UCH37". The EMBO Journal. 25 (24): ... "hRpn13/ADRM1/GP110 is a novel proteasome subunit that binds the deubiquitinating enzyme, UCH37". The EMBO Journal. 25 (24): ...
CYP1A1 is the enzyme responsible for the metabolic activation of PAHs. Persons with a high degree of CYP1A1 inducibility (phase ... In general PAH carcinogenesis involves activation by the enzyme P-450 to diol epoxide metabolites with an epoxide ring in the ... Benzo[c]fluorene is mainly metabolized by the CYP enzymes in the liver. There is also evidence that a larger number of ... It is possible that benzo[c]fluorene may have a unique (and still unknown) mechanism of activation or transportation, which ...
Jin J, Li X, Gygi SP, Harper JW (2007). "Dual E1 activation systems for ubiquitin differentially regulate E2 enzyme charging". ... Ubiquitin-like modifier-activating enzyme 6 is a protein that in humans is encoded by the UBA6 gene. GRCh38: Ensembl release 89 ... "Entrez Gene: UBE1L2 ubiquitin-activating enzyme E1-like 2". Hartley JL, Temple GF, Brasch MA (2001). "DNA Cloning Using In ... a novel E1 enzyme specific for ubiquitin". J Biol Chem. 282 (32): 23010-4. doi:10.1074/jbc.C700111200. PMID 17580310. " ...
2002). "The FX enzyme is a functional component of lymphocyte activation". Cell. Immunol. 213 (2): 141-148. doi:10.1006/cimm. ... GDP-mannose 4,6 dehydratase is an enzyme that in humans is encoded by the GMDS gene. GRCh38: Ensembl release 89: ... 1998). "Molecular cloning and expression of GDP-D-mannose-4,6-dehydratase, a key enzyme for fucose metabolism defective in ... short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative". Chem Biol Interact. 178 (1-3): 94-98. doi: ...
Activation of the Neurospora crassa enzyme by ammonium and rubidium ions". The Biochemical Journal. 209 (2): 527-31. doi: ... In plants, the enzyme can work in either direction depending on environment and stress. Transgenic plants expressing microbial ... The enzyme represents a key link between catabolic and anabolic pathways, and is, therefore, ubiquitous in eukaryotes. In ... As such it was one of the earliest enzymes to show what was later described as allosteric behavior. Mutations alter the ...
Leidecker O, Matic I, Mahata B, Pion E, Xirodimas DP (March 2012). "The ubiquitin E1 enzyme Ube1 mediates NEDD8 activation ... Jin J, Li X, Gygi SP, Harper JW (June 2007). "Dual E1 activation systems for ubiquitin differentially regulate E2 enzyme ... Ubiquitin-like modifier activating enzyme 1 (UBA1) is an enzyme which in humans is encoded by the UBA1 gene. UBA1 participates ... "Structural insights into E1-catalyzed ubiquitin activation and transfer to conjugating enzymes". Cell. 134 (2): 268-78. doi: ...
Jin J، Li X، Gygi SP، Harper JW (2007). "Dual E1 activation systems for ubiquitin differentially regulate E2 enzyme charging". ... UBE1L2‏ (Ubiquitin like modifier activating enzyme 6) هوَ بروتين يُشَفر بواسطة جين UBE1L2 في الإنسان.[1][2] ... FAT10 activating enzyme activity. • nucleotide binding. • نشاط ليغازي. • ربط بروتيني. • ATP binding. • ubiquitin-like modifier ... "Entrez Gene: UBE1L2 ubiquitin-activating enzyme E1-like 2". مؤرشف من الأصل في 13 أبريل 2010. الوسيط ,مسار الأرشيف=. تم تجاهله ( ...
The encoded enzyme is a negative regulator of thiopurine activation and toxicity. Mutations in this gene result in poor ... This gene encodes an enzyme that belongs to the Nudix hydrolase superfamily. Members of this superfamily catalyze the ...
Particular enzymes in the ubiquitin/proteasome pathway allow ubiquitination to be directed to some proteins but not others - ... During atrophy, there is a down-regulation of protein synthesis pathways, and an activation of protein degradation. The ...
"Nicotinamide mononucleotide activation of new DNA-dependent polyadenylic acid synthesizing nuclear enzyme". Biochem. Biophys. ... The first mammalian enzyme with poly-ADP-ribose transferase activity was discovered during the late 1980s. For the next 15 ... Upon activation, bAREs ADP-ribosylate any number of eukaryotic proteins; such mechanism is crucial to the instigation of the ... However, as more enzymes with the ability to ADP-ribosylate proteins were discovered, the multifunctional nature of ADP- ...
Adenylate Cyclase, Animals, Catalytic Domain, Cell Line, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, Enzyme Activation, ... Activation of these enzymes requires the dimerization of the catalytic domain and typically occurs under stress. Using a ... Specifically, activation of trypanosome adenylate cyclase resulting from parasite phagocytosis by liver myeloid cells inhibited ... the synthesis of the trypanosome-controlling cytokine tumor necrosis factor-α through activation of protein kinase A in these ...
Enzyme Activations. All MeSH CategoriesPhenomena and Processes CategoryChemical PhenomenaBiochemical PhenomenaEnzyme Activation ... Enzyme Activation. Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation ... conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. ... by ions (activators); 2, activation by cofactors (coenzymes); and 3, ...
Not only enzyme activation is subject of a less detailed presentation, but also enzyme inhibition and activation are very often ... I attempt to introduce a general model of enzyme inhibition and activation to allow one to interpret inhibition and activation ... Enzyme inhibition and activation: A general theory. *A. A. Saboury. 1. Journal of the Iranian Chemical Society volume 6, pages ... J. Stojan, Enzyme Inhibition, in: H.J. Smith, C. Simons (Eds.), Enzymes and Their Inhibition, Drug Development, CRC Press, ...
... followed by ubiquitin transfer to an E2-conjugating enzyme through a transthiolation reaction4,5,6,7. Charged E2s function with ... involves adenylation and thioesterification of the carboxy-terminal carboxylate of ubiquitin by the E1-activating enzyme Ube1 ( ... Dual E1 activation systems for ubiquitin differentially regulate E2 enzyme charging. *Jianping Jin1. , ... Figure 4: Distinct requirements for charging of the ubiquitin conjugating enzymes Use1 and Cdc34 in vivo.. ...
Conversely, malic enzymes keep p53 in check; loss of malic enzymes ramps up p53 activation and induces senescence via either ... in which activation of p53 suppresses malic enzyme expression, reducing malic enzyme levels and further upregulating p53, ... p53 activation suppresses malic enzyme expression and leads to senescence in pre-cancerous cells. *Download PDF Copy ... malic enzyme 1 and malic enzyme 2 (ME1 and ME2), could be involved. Malic enzymes recycle malate - an intermediate molecule - ...
Phosphoinositides in Subcellular Targeting and Enzyme Activation ?????? Stenmark Harald ... Phosphoinositides in Subcellular Targeting and Enzyme Activation ?????? ??? ??? ???? ?????? 3500 ...
This invention covers a new process that allows the stabilization and activation of sensi-tive catalysts (respectively enzymes ... Stabilization and Activation of Enzymes for synthesis in Organic Media. 03.08.2005 ...
Title: Peroxide Activation for Electrophilic Reactivity by the Binuclear Non-heme Iron Enzyme AurF ... Accepted Manuscript: Peroxide Activation for Electrophilic Reactivity by the Binuclear Non-heme Iron Enzyme AurF ... 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; O2 activation; diiron site; peroxo intermediate; nuclear resonance ... As a result, this activation of peroxide by protonation is likely also relevant to the reactive peroxo intermediates in other ...
Activation Energy and Enzyme Catalysis. Discussion of all aspects of biological molecules, biochemical processes and laboratory ... Activation Energy and Enzyme Catalysis. by roark » Sun Feb 25, 2007 9:58 am ... 4) How does (Gibbs) free energy of activation relate to activation energy and threshold energy? 5) From what I understand, by ... it seems like the enzyme is increasing rate without changing activation energy. 3) How does a potential energy profile relate ...
Enzymes greatly decrease the activation energy in 2 distinct ways:. i. Lowering required energy: An enzymes selective three ... Q: Enzymes greatly decrease the activation energy. Explain two of the way they do this and be specific in terms of chemical ... Enzymes and activation energy.. Discussion of all aspects of biological molecules, biochemical processes and laboratory ... From Wikipedia on Enzymes:. The mechanism of enzyme catalysis is similar in principle to other types of chemical catalysis. By ...
... binding of calcium ions change structure for activation ... Upon proteolysis, the enzyme exothermally acquires two more Ca( ... Three-dimensional structure of the human transglutaminase 3 enzyme: ... Three-dimensional structure of the human transglutaminase 3 enzyme: binding of calcium ions change structure for activation. * ... Three-dimensional structure of the human transglutaminase 3 enzyme: binding of calcium ions changes structure for activation.. ...
Dissociation of inositol-requiring enzyme (IRE1α)-mediated c-Jun N-terminal kinase activation from hepatic insulin resistance ... Dissociation of Inositol-requiring Enzyme (IRE1α)-mediated c-Jun N-terminal Kinase Activation from Hepatic Insulin Resistance ... Dissociation of Inositol-requiring Enzyme (IRE1α)-mediated c-Jun N-terminal Kinase Activation from Hepatic Insulin Resistance ... Dissociation of Inositol-requiring Enzyme (IRE1α)-mediated c-Jun N-terminal Kinase Activation from Hepatic Insulin Resistance ...
... January 10, 2010, Indiana ... 10 that the compound, called Alda-1, acts much like a shim to prop up a mutated form of a key enzyme, restoring the enzymes ... The enzyme, called ALDH2, plays an important role in metabolizing alcohol and other toxins, including those created by a lack ... Hurley likens to a woodworking procedure in which Alda-1 attaches to the ALDH2 enzyme at a crucial spot and acts like a shim or ...
... direct activation, and indirect activation. Include G proteins and find homework help for other Science questions at eNotes ... Enzymes are a type of protein, so membrane enzyme proteins are enzymes that are attached to a cellular membrane. They perform ... Enzymes are a type of protein, so membrane enzyme proteins are enzymes that are attached to a cellular membrane. They perform ... Describe the relationships between membrane channel proteins, membrane enzyme proteins, direct activation, and indirect ...
... iodothyronine deiodinase by von Hippel-Lindau protein-interacting deubiquitinating enzymes regulates thyroid hormone activation ... iodothyronine deiodinase by von Hippel-Lindau protein-interacting deubiquitinating enzymes regulates thyroid hormone activation ... hybrid screen of a human-brain library with D2 as bait identified von Hippel-Lindau protein-interacting deubiquitinating enzyme ...
VHL-interacting deubiquitinating enzyme (VDU); GAL4 activation domain (GAL4 AD); hemaglutinin (HA); GAL4 DNA binding domain ( ... Although hundreds of UBP enzymes have been cloned, only a few examples of substrate recognition by UBP enzymes have been ... DUB-1, a deubiquitinating enzyme with growth-suppressing activity. Proc. Natl. Acad. Sci. U. S. A. 1996. 93:3275-3279. View ... Antagonistic regulation of myogenesis by two deubiquitinating enzymes, UBP45 and UBP69. Proc. Natl. Acad. Sci. U. S. A. 2002. ...
Increased substrate accessibility or enzyme activation. Plant Physiology, 85(3), 693-698. DOI: 10.1104/pp.85.3.693 ... We propose that plasma membrane ATPase activation is due not solely to vesicle disruption and accessibility of ATP to the ...
Enzyme-instructed self-assembly leads to the activation of optical properties for selective fluorescence detection and ... Enzyme-instructed self-assembly leads to the activation of optical properties for selective fluorescence detection and ... Here, we show that enzyme-instructed self-assembly (EISA) is an ideal strategy to develop a both fluorescence and reactive ...
Quercetin Protects Primary Human Osteoblasts Exposed to Cigarette Smoke through Activation of the Antioxidative Enzymes HO-1 ... Primary human osteoblasts exposed to 100 μM Quercetin for 4 h were examined for expression of the anti-oxidative enzymes HO-1 ... Activation precedes resorption followed by reversal and formation. Osteoblasts in particular play a key role in this cycle. ... Figure 4: Quercetin protects primary human osteoblasts from CSM-induced damage via upregulation of anti-oxidative enzymes HO-1 ...
Spätzle-Processing Enzyme-independent Activation of the Toll Pathway in Drosophila Innate Immunity. Miki Yamamoto-Hino1), ... Spätzle-processing enzyme (SPE) is the only enzyme identified to date that functions in converting Spätzle to an active form ... In the present study, Toll activation induced by immune challenge was almost suppressed in spätzle mutant larvae and adults, ...
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Centers RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.. ...
A catalytically dead paralog activates its cognate enzyme through an allosteric mechanism that combined structural and ... Mechanistic model of prozyme-induced TbAdoMetDC enzyme activation.. The model depicts a logical step-wise process assuming that ... Relief of autoinhibition by conformational switch explains enzyme activation by a catalytically dead paralog. ... Thank you for submitting your article "Relief of autoinhibition by conformational switch explains enzyme activation by a ...
UV radiation and enzyme inhibitors in a time and dose dependent manner and looked at the resulting enzyme activation rates of ... Elucidation of the enzyme activation kinetics in a time and dose dependent manner of the proteins governing cell fate decision ... Here we explored the kinetics of activation of these key enzymes, the rates of their product formation and the interplay ... Abstract 3103: Differences in the DDR enzymes activation kinetics between normal and cancer cells could be utilized to achieve ...
... as an enzyme that induces NLRP1B degradation and activation. Our results provide a unified mechanism for NLRP1B activation by ... Functional degradation: A mechanism of NLRP1 inflammasome activation by diverse pathogen enzymes ... Functional degradation: A mechanism of NLRP1 inflammasome activation by diverse pathogen enzymes ... Functional degradation: A mechanism of NLRP1 inflammasome activation by diverse pathogen enzymes ...
... well learn how enzymes function to lower the activation energy of a chemical reaction. Enzymes bind to their substrates to ... What your cells have to help overcome a problem of high activation energy are called enzymes. Enzymes are proteins that lower ... In summary, enzymes are proteins that lower the activation energy of a chemical reaction. Enzymes are not consumed or produced ... Video: Function of Enzymes: Substrate, Active Site & Activation Energy. In this lesson, well learn how enzymes function to ...
  • The aim of the study was to determine the effect of carboxylesterase 1 (CES1) genetic variation on the activation of angiotensin-converting enzyme inhibitor (ACEI) prodrugs. (ovid.com)
  • Concomitantly, it lowered the increased protein levels of angiotensin-converting enzyme (ACE), p22phox and cleaved caspase-3 and prevented the aorta histological and ultrustructural abnormalities induced by MI. (qxmd.com)
  • We evaluated the effects of activation of endogenous angiotensin converting enzyme (ACE) 2 on the early stages of DR. Rats were administered an intravenous injection of streptozotocin to induce hyperglycemia . (bvsalud.org)
  • Chymase has been shown to be a key enzyme in the local renin-angiotensin system (RAS) that generates angiotensin II (Ang II) independently from angiotensin-converting enzyme (ACE). (aspetjournals.org)
  • The highest enzymatic levels for these enzymes were achieved at 48 hours in plantlets elicited with COS and at 72 hours for those plants treated with chitosan polymer, while the highest POD (EC 1.11.1.6) activity was detected with CH between 48 and 72 hours. (scirp.org)
  • The obtained results show that only high concentrations and large sizes of Dextran reduce both constants suggesting a mixed activation-diffusion control of this enzymatic reaction due to the Dextran crowding action. (ub.edu)
  • From our knowledge, this is the first experimental study that depicts mixed activation-diffusion control in an enzymatic reaction due to the effect of crowding. (ub.edu)
  • again, a very good example of synergism within the system and, also, a very good reason taking isolated enzyme factors may be disruptive of normal enzymatic activity causing fluctuations of precise temperature ranges necessary to conclude successfully an important metabolic process. (rawfoodexplained.com)
  • An oxygen sensitive coating such as a fluorescent dye is provided on the enzyme optrode in close proximity with the enzymatic reaction, and also on a reference optrode at a position spaced substantially from the enzymatic reaction. (google.com.au)
  • NAD(P)H dependent oxidase derived-reactive oxygen species (ROS) due to activation of the renin-angiotensin-aldosterone system (RAAS) in blood vessels postmyocardial infarction MI or during the HF leads to endothelium dysfunction and enhanced apoptosis. (qxmd.com)
  • and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. (nih.gov)
  • Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic acid residues to produce two subunits, large and small, that dimerize to form the active enzyme. (cancerindex.org)
  • Chymase is stored in mast cells in an inactive form and is released as an active enzyme when mast cells are stimulated by injury or inflammation. (aspetjournals.org)
  • a Specific activities are calculated as the means for five assays of each of two independent batches of enzyme for FrxA and RdxA. (asm.org)
  • In assays of NAD kinase and myosin light chain kinase activation some differences between bovine calmodulin and bacterial control calmodulin were observed. (utah.edu)
  • No differences between bovine and control calmodulins were observed in assays of calcineurin activation or peptide binding. (utah.edu)
  • Upon proteolysis, the enzyme exothermally acquires two more Ca(2+) ions that activate the enzyme, are exchangeable and are functionally replaceable by other lanthanide trivalent cations. (rcsb.org)
  • This technique also strongly inactivated the enzyme but did not generate membrane-active phospholipid degradation products. (biochemj.org)
  • The greater susceptibility of 5′-monophosphorylated RNAs to cleavage by these enzymes may help to ensure the rapid degradation of the downstream products of initial endonucleolyic cleavage, which differ from their primary-transcript precursors in being 5′-monophosphorylated rather than 5′-triphosphorylated. (pnas.org)
  • Among the assayed enzymes involved in the degradation, phospholipase D (PLD) and lipolytic acyl hydrolase were activated at the early part of starvation, and these activities were followed by β-oxidation and the glyoxylate cycle enzymes in order. (plantphysiol.org)
  • Activation of lipid peroxidation, suggestive of cell death, occurred immediately after the decrease of the phospholipid degradation, suggesting that the observed phospholipid catabolic pathway is part of the metabolic strategies by which cells effectively survive under Glc starvation. (plantphysiol.org)
  • Transglutaminase (TGase) enzymes catalyze the formation of covalent cross-links between protein-bound glutamines and lysines in a calcium-dependent manner, but the role of Ca(2+) ions remains unclear. (rcsb.org)
  • The phosphorus in your diet works to regulate hormone and enzyme activity and also gets used to maintain healthy cell membranes and produce DNA. (sfgate.com)
  • They perform regular enzyme type functions including the synthesis or breaking down of biomolecules. (enotes.com)
  • Conversion of an inactive form of an enzyme to one possessing metabolic activity. (nih.gov)
  • Catalytically inactive enzyme paralogs occur in many genomes. (elifesciences.org)
  • The interleukin-1β (IL-1β) converting enzyme (ICE) processes the inactive IL-1β precursor to the proinflammatory cytokine. (sciencemag.org)
  • These cells were immortalised by transduction with the SV40 Large T antigen, then transduced with lentiviral vectors expressing either enzyme active or inactive FAP. (edu.au)
  • Most enzymes actually exist in an inactive form until such time as their catalytic talents are called upon by the organisms. (rawfoodexplained.com)
  • Despite this structural difference, inactive samples of DgAOR can be activated upon incubation with dithionite plus sulfide, a procedure similar to that used for activation of desulfo-XO. (conicet.gov.ar)
  • Stimulation of TAK1 causes activation of NF-kappaB, which is blocked by dominant-negative mutants of NIK, and an inactive TAK1 mutant prevents activation of NF-kappaB that is mediated by IL-1 but not by NIK. (nih.gov)
  • 7) One of the most basic ways in which an enzyme works is by providing a space for its reactants to come close together in the proper orientation. (biology-online.org)
  • Amylase is an enzyme in saliva that breaks starch into glucose monomers. (indiana.edu)
  • We exposed normal (MCF10A, HaCat) and breast cancer cell lines (MCF7, MDA MB231, MDA MB468) to different combinations of radiomimetic drugs, UV radiation and enzyme inhibitors in a time and dose dependent manner and looked at the resulting enzyme activation rates of DDR kinases such as ATM, ATR, Chk1, Chk2, and DDR phosphatases PP2A and WIP1. (aacrjournals.org)
  • Yang's team found that p53 inhibits malic enzyme expression, such that loss of p53 causes malic enzyme abundance to increase. (news-medical.net)
  • Overexpression of malic enzymes inhibits senescence. (news-medical.net)
  • On the other hand, upregulation of malic enzymes inhibits p53. (news-medical.net)
  • Also cyclophosphamide and specially cytarabine cause significant increase in activation and expression of GALNT11 which inhibits glycosylation and tumorogenesis dependent signaling pathway. (ac.ir)
  • One of the fractionated compounds showed potent inhibition against COX enzymes with no inhibition against 5-LOX. (isharonline.org)
  • The booklet discusses topics linked to international compound metabolizing enzymes with emphasis on biochemical facets, together with lipophilic overseas compounds, catalytic houses, reactive intermediates, biomedical and biochemical results, genetic polymorphisms, enzyme inducibility, enzyme modulation for well-being merits, nutritional similar enzyme modulators, and structural features of enzyme inducers. (msk.ru)
  • Enzymes are very specialized organic compounds of polymers of amino acids. (rawfoodexplained.com)
  • Mononuclear Mo-containing enzymes of the xanthine oxidase (XO) family catalyze the oxidative hydroxylation of aldehydes and heterocyclic compounds. (conicet.gov.ar)
  • The faulty oxygenation of xenobiotic compounds leads to the formation of reactive oxygen species (ROS) after O2 activation. (eawag.ch)
  • Using dioxygenases that are capable of oxygenating nitroaromatic compounds, we plan to establish quantitative relationships for the ``efficiency'' with which these enzymes incorporate molecular O2 into the aromatic contaminants vs. the amount of O2 that ends up in reactive oxygen species. (eawag.ch)
  • To explore fatty acid tailoring enzymes of the calcium-dependent antibiotic (CDA) biosynthetic pathway, this strategy enabled the transformation of modified fatty acids, covalently bound as thioesters to an ACP, into amide ligation products that can be directly analyzed and compared to synthetic standards by HPLC-MS. The driving force of the amide formation is the thermodynamic activation inherent to thioester-bound compounds. (figshare.com)
  • Proteases such as anthrax lethal factor can activate an inflammasome known as NLRP1B, but the mechanism for this activation has been unclear. (sciencemag.org)
  • It is known that cysteine proteases from plants, like bromelain and papain are capable to suppress inflammatory activation. (biomedcentral.com)
  • What are enzymes and two proteases with redundant functions during apoptosis may autocatalytic processing little known about the function the short for the early activation caspase3 enzyme that required for sipa cleavage specific recognition motif that divides the protein into its functional. (informe.com)
  • As a result, this activation of peroxide by protonation is likely also relevant to the reactive peroxo intermediates in other binuclear non-heme iron enzymes. (osti.gov)
  • Here, we show that enzyme-instructed self-assembly (EISA) is an ideal strategy to develop a both fluorescence and reactive oxygen species (ROS) generation capability activatable probe with aggregation-induced emission (AIE) signature. (rsc.org)
  • CCl 4 exposure increased the activities of various serum maker enzymes and intracellular reactive oxygen species (ROS) production. (hindawi.com)
  • This gene encodes a member of the cysteine-aspartic acid protease (caspase) family of enzymes. (cancerindex.org)
  • cAMP-specific 3',5'-cyclic phosphodiesterase 4D is an enzyme that in humans is encoded by the PDE4D gene. (wikipedia.org)
  • Simulations were performed on the full enzyme complex and on the membrane embedded parts alone. (figshare.com)
  • We have evidence that a mediator of glucose uptake, HIF1α, expression was dependent on IL-15 induced STAT3 activation. (frontiersin.org)
  • In a preferred form, an enzyme optrode comprises an optical fiber with an enzyme coating such as glucose oxidase for catalyzing glucose in the presence of oxygen (O 2 ) to produce gluconic acid and hydrogen peroxide. (google.com.au)
  • 6. The glucose sensor of claim 1 wherein said enzyme coating is glucose oxidase. (google.com.au)
  • Among the molecular mechanisms that could account for these properties are those in which 5′-end binding by one enzyme subunit induces a protein structural change that accelerates RNA cleavage by another subunit. (pnas.org)
  • loss of malic enzymes ramps up p53 activation and induces senescence via either downregulation of a p53 inhibitor (Mdm2) or production of oxygen radicals. (news-medical.net)
  • These studies indicate that the inhibitor binds to the enzyme at the active site. (ac.ir)
  • A two-step inhibition was observed, first the inhibitor reacts with the enzyme on one site- non-cooperative with Mg 2+ , and TPP, inhibiting the enzyme, second in higher concentration of the inhibitor an abrupt enhancement of the inhibition takes place. (ac.ir)
  • Further-more, the interleukin-1b-converting enzyme inhibitor, Ac-YVAD-CMK, reversed the augmented cytotoxicity. (pdfslide.tips)
  • MLN4924 disrupts NF-κB activation and induces Bim expression in CLL cells, thereby preventing stroma-mediated resistance. (aacrjournals.org)
  • Both enzymes are profoundly activated (~1000 fold increase in catalytic efficiency) by oligomerization with their paralogous pseudoenzyme leading to formation of catalytically functional complexes. (elifesciences.org)
  • Enzyme affinity and efficiency. (unibo.it)
  • The key objective is to present a comprehensive analysis of the current market and its future direction in the enzymes market as an important tool for increasing the efficiency and specificity of the products in which the enzymes are used. (bio-medicine.org)
  • Enzyme compatibility with the environment in addition to their ability to increase process efficiency and provide product specificity has enhanced the enzymes market globally. (bio-medicine.org)
  • However, it is not known the systemic behavior of defensive enzymes activated by these elicitors. (scirp.org)
  • In this work, the dynamic behavior of key defensive enzymes was evaluated in to- bacco plant leaves previously treated through the roots with chitosan polymer (CH), chitosan (COS) and pectic (OGAS) oligosaccharides and Spermine (Sp). (scirp.org)
  • Offers an understanding of the behavior of enzyme systems and the diagnostic tools used to characterize them and determine kinetic mechanisms. (ecampus.com)
  • It the temperature which the enzymes function best the temperature which the. (informe.com)
  • However, the large reductions in ΔH⧧ were partially offset by a decrease in TΔS⧧ and unexpectedly accompanied by a negative activation heat capacity, signaling strong adaptation to the operating temperature. (bristol.ac.uk)
  • The computed potential energy surfaces rationalize the observed negative temperature dependences in terms of a chemical activation mechanism, and the possibility that an energized adduct may contribute to product formation is investigated via RRKM theory. (unt.edu)
  • However, small quantities of lysophosphatides were still associated with the delipidated fractions after extraction with albumin and might have influenced the inactivation and re-activation observed. (biochemj.org)
  • We now report a combined kinetic and X-ray crystallographic study to unveil the enzyme modification responsible for the inactivation and the chemistry that occurs at the Mo site when Dg AOR is activated. (conicet.gov.ar)
  • By doing so they prevent GTP-dependent activation and simultaneously expose the target threonines on the switch I loop for phosphorylation by ROP18, resulting in permanent inactivation of the protein. (nih.gov)
  • Quercetin increased the expression of the anti-oxidative enzymes heme-oxygenase- (HO-) 1 and superoxide-dismutase- (SOD-) 1. (hindawi.com)
  • AST protected ARPE-19 cells against H 2 O 2 -induced oxidative stress via Nrf2-mediated upregulation of the expression of Phase II enzymes involving the PI3K/Akt pathway. (molvis.org)
  • The main problem the scientists found was an enzyme called ADAR1 (adenosine deaminase acting on RNA1), which mediates post-transcriptional adenosine-to-inosine (A-to-I) RNA editing. (pharmaceuticalintelligence.com)