Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.3.1 (Mg2+-ATPase)
1,484 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ca2+-dependent phosphorylation of the myosin light chains in bovine aortic native actomyosin is markedly depressed in the presence of cyclic AMP and its dependent protein kinase. This inhibition occurs with either cardiac, skeletal, or aortic protein kinase plus cyclic AMP, while little or no inhibition occurs with either cyclic AMP or protein kinase alone. The extent of inhibition is related to the concentration of protein kinase and approaches a maximum of approximately 50%. Concomitant with the inhibition of myosin light chain phosphorylation is (a) an increased phosphorylation of a 100,000-dalton moiety which possibly corresponds to the myosin light chain kinase present in the native actomyosin preparation and (b) a decrease in the actomyosin Mg2+-ATPase activity. These findings suggest that modulation of actin-myosin interactions by the cAMP system directly at the level of the contractile proteins may represent a mechanism by which beta adrenergic relaxation occurs in mammalian vascular smooth muscle.
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PMID:Adenosine 3':5'-monophosphate-mediated inhibition of myosin light chain phosphorylation in bovine aortic actomyosin. 22 48

We have examined the effects on the activities of three calmodulin-dependent enzymes (cAMP phosphodiesterase, caldesmon kinase and myosin light chain kinase) of the dihydropyridine Ca2+ channel blocker felodipine and three analogues (p-chloro, oxidized and t-butyl) exhibiting different pharmacological potencies. The cAMP phosphodiesterase was inhibited completely by felodipine and the p-chloro analogue with IC50 values of 3.7 and 1.5 microM respectively. The oxidized and t-butyl analogues were relatively ineffective in inhibiting cAMP phosphodiesterase. Felodipine and the p-chloro analogue inhibited the basal (Ca2+/calmodulin-independent) activity of cAMP phosphodiesterase as well as the calmodulin-stimulated activity. Calmodulin was relatively ineffective in preventing inhibition of cAMP phosphodiesterase by felodipine and the p-chloro analogue. These observations suggest that felodipine may act directly on the phosphodiesterase as well as through calmodulin. Felodipine and the p-chloro analogue inhibited Ca2+/calmodulin-dependent caldesmon kinase with similar potencies (IC50 = 17.4 microM), whereas the oxidized and t-butyl analogues caused no inhibition. Similarly, felodipine and the p-chloro analogue inhibited myosin light chain kinase activity whether the isolated 20 kD light chain (IC50 = 12.6 microM) or intact myosin (IC50 = 11.0 microM) was used as substrate. Inhibition in each case was prevented by excess calmodulin. The oxidized and t-butyl derivatives caused little or no inhibition. Finally, the effects of felodipine and the three analogues on two processes which are dependent on myosin phosphorylation were examined, namely the actin-activated Mg2+-ATPase activity of myosin and the assembly of myosin filaments. Felodipine and the p-chloro analogue inhibited the actin-activated Mg2+-ATPase activity of smooth muscle myosin (IC50 = 25.1 microM). The oxidized and t-butyl analogues exhibited no inhibition. Similarly, felodipine and the p-chloro analogue blocked myosin filament assembly induced by low concentrations of calmodulin, whereas the oxidized and t-butyl analogues did not. Again, inhibition of the actin-activated myosin Mg2+-ATPase and myosin filament assembly by felodipine and the p-chloro analogue could be reversed by raising the calmodulin concentration. These observations suggest that some of the pharmacological actions of felodipine on smooth muscle may involve inhibition of calmodulin-dependent enzymes which are functionally involved in the regulation of smooth muscle contraction.
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PMID:Effects of felodipine (a dihydropyridine calcium channel blocker) and analogues on calmodulin-dependent enzymes. 283 1

Tryptic modification appears to potentiate activation of the Ca2+ channels of isolated sarcoplasmic reticulum vesicles. In the presence of 1 mM free Mg2+ we observe that: 1) cAMP and doxorubicin activation of passive efflux from tryptically modified vesicles is approximately 20-fold greater than from native SR. 2) Ruthenium red inhibits Ca2+ efflux from modified vesicles. 3) The binding affinities and Hill coefficients of activation of efflux by cAMP and doxorubicin are the same in modified vesicles as in native vesicles. 4) Proteolysis stimulates passive efflux from heavy SR much more than from light SR. 5) Stimulation of cAMP- and doxorubicin-activated Ca2+ release is biphasic, whereas Hg2+-activated Ca2+ efflux is monophasic. 6) In the absence of Mg2+, the Ca2+ dependence of cAMP-activated efflux from tryptically modified vesicles is similar to that of native vesicles, with peak efflux rates occurring between approximately 1 and 10 microM Ca2+. 7) The Mg2+ dependence of efflux from modified vesicles is similar to that of native vesicles. 8) SDS-polyacrylamide gels indicate that the Ca2+, Mg2+-ATPase and the high molecular weight ryanodine receptor are both cleaved faster than the stimulation of efflux.
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PMID:Limited tryptic modification stimulates activation of Ca2+ release from isolated sarcoplasmic reticulum vesicles. 284 65

Two hours after administration of Soman (120 micrograms/kg, s.c.), Sarin (150 micrograms/kg, s.c.), or Tabun (240 micrograms/kg, s.c.), microsomes and cytosol were prepared from rat striata. Microsomal and cytosolic calmodulin (CaM) levels, microsomal adenylate and guanylate cyclase activities, protein kinase activities, and Ca2+ + Mg2+-ATPase activities were determined while cytosolic phosphodiesterase (PDE) activities were determined. CaM levels in both cell fractions were significantly increased by Soman and Sarin. Cyclic AMP-PDE and adenylate cyclase activities were decreased by Soman and Sarin. All three agents decreased activities of cyclic GMP-PDE and guanylate cyclase. Sarin and Tabun administration caused significant increases in microsomal protein kinase activity and none of the agents affected activity of divalent cation ATPases. The intensity of effects of the three organophosphates roughly paralleled their observed neurotoxic potencies. The results indicate that components of the CaM system are implicated as either causative or adaptive changes induced by these agents.
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PMID:Acute effects of soman, sarin, and tabun on microsomal and cytosolic components of the calmodulin system in rat striatum. 286 34

Ciliary activity is regulated by Ca2+ and cyclic nucleotides, but the molecular mechanisms of the regulation are unknown. We have tested the ability of Ca2+ and cyclic nucleotides to alter ciliary Mg2+-ATPase or to stimulate phosphorylation of axonemal dynein. Mg2+-ATPase activity in cilia and axonemes from Paramecium was stimulated 2-fold by micromolar Ca2+, but this Ca2+ sensitivity was lost upon solubilization of the dyneins from the axoneme. The Ca2+-sensitive component of ciliary Mg2+-ATPase activity was inhibited by the dynein inhibitors vanadate and Zn2+, but was insensitive to the calmodulin antagonists calmidazolium and melittin. Dynein activity in the high-salt extract from axonemes was also insensitive to calmidazolium. Calmodulin did not sediment with 22 S or 12 S dyneins on sucrose gradients containing Ca2+, but it did sediment in the region from 19 S to 14 S. Mg2+-ATPase activity in ciliary fractions was unaltered in the presence of cAMP or cGMP. However, polypeptides associated with the 22 S and 12 S dyneins, as well as proteins of 19 S, 15 S, and 8 S, were substrates for endogenous ciliary kinases. High molecular weight polypeptides that sedimented at 22 S and 19 S were phosphorylated in a cyclic nucleotide-stimulated manner.
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PMID:Regulation of axonemal Mg2+-ATPase from Paramecium cilia: effects of Ca2+ and cyclic nucleotides. 296 17

Contraction of tracheal smooth muscle requires the binding of Ca2+ to calmodulin, which then binds to and activates MLCK. The Ca2+-calmodulin-MLCK complex catalyzes the phosphorylation of myosin, which causes contraction by stimulating actin-activated Mg2+-ATPase activity of myosin. Myosin phosphorylation appears to be a transient event that is responsible for a high velocity of shortening. The mechanism responsible for maintenance of isometric force is unknown, although a second Ca2+-dependent mechanism with a greater sensitivity to Ca2+ than the activation of MLCK has been hypothesized. Force would be maintained through the slow cycling of nonphosphorylated cross-bridges or a small population of phosphorylated cross-bridges. Tracheal smooth muscle utilizes both extracellular and intracellular pools of Ca2+ for contraction. Moreover, the membrane channels through which extracellular Ca2+ passes have been subdivided into potential-dependent channels (PDCs) and receptor-operated channels (ROCs) independent of membrane potential. The relative extent to which extracellular and intracellular sources of Ca2+ as well as PDCs and ROCs are utilized depends on the agonist used for contraction, its concentration, and the type and location of the smooth muscle being investigated. Calcium antagonists such as verapamil and nifedipine, which reportedly block PDCs but not ROCs, are much better inhibitors of tracheal smooth muscle contractions induced by serotonin than those induced by acetylcholine, histamine, and leukotriene D4, indicating an effect of these latter three agents on ROCs. Relaxation of tracheal smooth muscle following stimulation of beta-adrenergic receptors most likely results from an increase in cAMP that stimulates a cAMP-dependent protein kinase to catalyze a protein phosphorylation that leads to relaxation by decreasing the intracellular concentration of Ca2+. The primary mechanisms whereby cAMP is thought to reduce intracellular Ca2+ to effect relaxation include: activation of a calmodulin-sensitive Ca2+ ATPase in the plasma and sarcoplasmic reticulum membranes, and extrusion of Ca2+ by a Na+-Ca2+ exchange mechanism coupled to Na+-K+-ATPase in the cell membrane. A more controversial mechanism for relaxation that bypasses Ca2+ might involve the dephosphorylation of myosin. Leukotrienes are released by various stimuli, including immunologic challenge, and have been considered as important mediators of bronchoconstriction in allergic asthma.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Tracheal smooth muscle. 301 93

A Dictyostelium discoideum myosin heavy chain kinase has been purified 14,000-fold to near homogeneity. The enzyme has a Mr = 130,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and greater than 700,000 as determined by gel filtration on Bio-Gel A-1.5m. The enzyme has a specific activity of 1 mumol/min X mg when assayed at a Dictyostelium myosin concentration of 0.3 mg/ml. A maximum of 2 mol of phosphate/mol of myosin is incorporated by the kinase, and the phosphorylated amino acid is threonine. Phosphate is incorporated only into the myosin heavy chains, not into the light chains. The actin-activated Mg2+-ATPase of Dictyostelium myosin is inhibited 70-80% following maximal phosphorylation with the kinase. The myosin heavy chain kinase requires 1-2 mM Mg2+ for activity and is most active at pH 7.0-7.5. The activity of the enzyme is not significantly altered by the presence of Ca2+, Ca2+ and calmodulin, EGTA, cAMP, or cGMP. When incubated with Mg2+ and ATP, phosphate is incorporated into the myosin heavy chain kinase, perhaps by autophosphorylation.
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PMID:Purification and characterization of a myosin heavy chain kinase from Dictyostelium discoideum. 302 76

Nuclear membranes of bovine corpora lutea contain nucleoside triphosphatase (NTPase), an enzyme involved in the nucleocytoplasmic transfer of mRNA. Upon addition to nuclear membranes, hCG stimulated this enzyme, but not Mg2+-ATPase or NADH cytochrome c reductase, in a dose-, time-, and temperature-dependent manner. Heat-denatured hCG, however, had no effect on NTPase activity. hCG antisera blocked hCG's ability to stimulate the NTPase activity. While human LH also stimulated luteal nuclear membrane NTPase activity, a variety of other hormones tested, including alpha- and beta-subunits of hCG and 1 and 10 mM cAMP, had no effect on the enzyme. hCG's effect on NTPase is tissue specific in that it had no effect on liver or kidney nuclear membrane NTPase activity. In conclusion, the present data demonstrate that hCG acts directly on the luteal cell nucleus, thus raising the possibility that internalized hCG might influence nuclear functions before it is eventually degraded in lysosomes of luteal cells.
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PMID:Direct stimulation of nucleoside triphosphatase activity in bovine luteal nuclear membranes by human chorionic gonadotropin. 303 92

We have partially purified myosin light chain kinase (MLCK) and myosin light chain phosphatase (MLCP) from Dictyostelium discoideum. MLCK was purified 4,700-fold with a yield of approximately 1 mg from 350 g of cells. The enzyme is very acidic as suggested by its tight binding to DEAE. Dictyostelium MLCK has an apparent native molecular mass on HPLC G3000SW of approximately 30,000 D. Mg2+ is required for enzyme activity. Ca2+ inhibits activity and this inhibition is not relieved by calmodulin. cAMP or cGMP have no effect on enzyme activity. Dictyostelium MLCK is very specific for the 18,000-D light chain of Dictyostelium myosin and does not phosphorylate the light chain of several other myosins tested. Myosin purified from log-phase amebas of Dictyostelium has approximately 0.3 mol Pi/mol 18,000-D light chain as assayed by glycerol-urea gel electrophoresis. Dictyostelium MLCK can phosphorylate this myosin to a stoichiometry approaching 1 mol Pi/mol 18,000-D light chain. MLCP, which was partially purified, selectively removes phosphate from the 18,000-D light chain but not from the heavy chain of Dictyostelium myosin. Phosphatase-treated Dictyostelium myosin has less than or equal to 0.01 mol Pi/mol 18,000-D light chain. Phosphatase-treated myosin could be rephosphorylated to greater than or equal to 0.96 mol Pi/mol 18,000-D light chain by incubation with MLCK and ATP. We found myosin thick filament assembly to be independent of the extent of 18,000-D light-chain phosphorylation when measured as a function of ionic strength. However, actin-activated Mg2+-ATPase activity of Dictyostelium myosin was found to be directly related to the extent of phosphorylation of the 18,000-D light chain. MLCK-treated myosin moved in an in vitro motility assay (Sheetz, M. P., and J. A. Spudich, 1983, Nature (Lond.), 305:31-35) at approximately 1.4 micron/s whereas phosphatase-treated myosin moved only slowly or not at all. The effects of phosphatase treatment on the movement were fully reversed by subsequent treatment with MLCK.
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PMID:Myosin light chain kinase and myosin light chain phosphatase from Dictyostelium: effects of reversible phosphorylation on myosin structure and function. 303 87

We previously reported that nuclei isolated from ovaries of premenopausal women contain binding sites for hCG/human LH (hLH). This study was undertaken to determine the possible functional significance of these nuclear binding sites. Upon addition to isolated ovarian (mostly luteal cells) nuclear membranes, hCG and hLH stimulated nucleoside triphosphatase (NTPase), an enzyme involved in nucleocytoplasmic transfer of mRNA, but not Mg2+-ATPase or NADH cytochrome c reductase activities, in a concentration-dependent manner. Heat-denatured hCG, isolated alpha- and beta-subunits of hCG, human FSH, PRL, and porcine relaxin had no effect on the enzyme. Addition of hCG antiserum blocked hCG's ability to stimulate NTPase activity. cAMP, which is a second messenger in hCG- and hLH-stimulated steroidogenesis, had no effect on NTPase activity. These results, which demonstrate that hCG acts on human ovarian nuclei directly, raise the possibility that internalized hCG might influence nuclear function(s) before it is eventually degraded in the lysosomes of ovarian cells.
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PMID:Direct stimulation of nucleoside triphosphatase activity in human ovarian nuclear membranes by human chorionic gonadotropin. 303 4


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