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

---

Query: EC:3.1.3.16 (calcineurin)
17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An inhibitor (inhibitor-1) of phosphorylase a phosphatase has been identified in rat epididymal fat pads. This heat-stable, acid-soluble protein only exhibits phosphatase inhibitory activity when it itself is phosphorylated. Inhibitor-1 in rat adipose tissue migrates at 32,000 Da on sodium dodecyl sulfate-polyacrylamide gels, and at 64,000 Da on gel filtration. Exposure of fat pads to insulin (1 milliunit/ml) resulted in a 50% decrease in inhibitor-1 activity, compared to control (p less than 0.001). Isoproterenol (10(-6) M) caused a 25% increase in inhibitor-1 activity (p less than 0.05). Electrophoresis of heat-stable proteins prepared from hormone-treated 32P-labeled fat cells showed that insulin caused a dephosphorylation of the 32,000 Da phosphoprotein by 30% (p less than 0.01), whereas isoproterenol stimulated 32P incorporation in this protein by 35% compared to control (p less than 0.05). Thus, insulin appears to dephosphorylate and inactivate inhibitor-1, and might thereby result in an increase of protein phosphatase activity. Insulin regulation of inhibitor-1 is a mechanism which may underlie other of insulin's effects in adipose tissue, such as the activation of glycogen synthase.
...
PMID:Hormonal regulation of protein dephosphorylation. Identification and hormonal regulation of protein phosphatase inhibitor-1 in rat adipose tissue. 634 43

Three stages of development of hepatic glycogen metabolism in the rat were studied. These included the last stage of gestation, in which large scale synthesis and accumulation of glycogen takes place, the perinatal period of glycogenolysis, and the suckling period up to and including weaning. The role of insulin in the regulation of the key rate-limiting enzymes of glycogen synthesis (glycogen synthase) and glycogen breakdown (glycogen phosphorylase) was studied as was the role of the key phosphoprotein phosphatase enzymes that regulate activation of synthase (synthase phosphatase) and inactivation of phosphorylase (phosphorylase phosphatase). Glycogen accumulates in significant quantities on days 20-21 of gestation in the rat (term, 22 days). Associated with this increased rate and amount of glycogen accumulation is an increase in glycogen synthase a and synthase phosphatase and phosphorylase phosphatase activities associated with the endoplasmic reticulum (ER). Concomitantly, fetal insulin levels are elevated as is the insulin to glucagon molar ratio and the synthase a/phosphorylase a ratio. At birth, these hepatic glycogen stores are rapidly degraded, and synthase a levels are diminished, as are ER-associated synthase phosphatase and phosphorylase phosphatase activities. Phosphorylase a levels are markedly elevated at this time as well. Insulin levels are decreased, as is the insulin to glucagon molar ratio. Gradually over a period of 4 weeks after birth, glycogen levels increase in the liver, accompanied by increased ER-associated phosphatase activities and an increased insulin to glucagon molar ratio. The data support a role for increased ambient insulin concentrations in regulation of the periods of active glycogen synthesis and accumulation in pre- and postnatal rat liver. A possible site of action of insulin is the ER and associated phosphoprotein phosphatase activities.
...
PMID:Regulation of hepatic glycogen metabolism in pre- and postnatal rats. 640 92

A standard preparation of phosphorylase kinase from rabbit skeletal muscle contains 2 mol of phosphoserine/mol of alpha beta gamma delta. This basal stoichiometry is not influenced by application of propranolol and insulin in vivo; these serine phosphates could not be hydrolyzed by phosphatases of the muscle extract or by alkaline phosphatases. When the enzyme is purified in the presence of the protein phosphatase inhibitor sodium fluoride, it contains either 1 or 3 additional mol of phosphoserine/mol of alpha beta gamma delta, termed phosphatase-sensitive phosphates. Both classes of phosphates yield in formic acid one single 31P NMR signal of a narrow line width (approximately 3 Hz) very similar in chemical shift to free phosphoserine. Phosphoserine is also identified by its chemical shift when dissolved in 8 M guanidinium chloride and by its electrophoretic mobility after acid hydrolysis. By self-phosphorylation of phosphorylase kinase, 14 additional mol of phosphate/mol of alpha beta gamma delta was incorporated, and all were identified as phosphoserine by 31P NMR spectroscopy. In native phosphorylase kinase, the 31P NMR signals of both the basal and the phosphatase-sensitive phosphates are substantially broadened and reduced in intensity, indicating strong interactions of the phosphate groups with the protein. The basal and phosphatase-sensitive phosphates give in 8 M guanidinium chloride a homogeneous NMR signal above pH 6; it splits into a doublet below pH 6 and into a triplet below pH 5.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Nonactivated phosphorylase kinase is a phosphoprotein: differentiation of two classes of endogenous phosphoserine residues by phosphorus-31 nuclear magnetic resonance spectroscopy and phosphatase sensitivity. 641 71

The following article provides evidence that cellular calcium controls the activity of glycogen synthase in all three major glycogen storage tissues; muscle, fat, and liver. Depletion of cellular calcium resulted in a moderate increase of glycogen synthase %I activities in intact mouse diaphragms, in isolated rat adipocytes, and in rat hepatocytes. The increase in %I activity of glycogen synthase was more pronounced when the uridine di-phosphoglucose concentration in the glycogen synthase assay was lowered from 4.4 mM to 0.2 mM. Calcium depletion resulted in an approximately two-fold decrease in the Ka values for glucose-6-phosphate in all three tissues. The activities of glycogen synthase also correlated well with the content of cell-associated calcium in rat hepatocytes. The glucose-6-phosphate independent activities of glycogen synthase in extracts of calcium-replete and calcium-depleted tissue approached the same value following the exposure to crude phosphoprotein phosphatase. The activities of glycogen phosphorylase decreased in calcium-depleted tissues and cells. Insulin stimulated the activity of glycogen synthase in muscle and fat in the absence of added sugar and in the absence of extracellular calcium. It is concluded that glycogen synthase is under the control of calcium in the three main glycogen storage tissues. The actions of calcium are probably mediated through the actions of calcium-sensitive protein kinase(s).
...
PMID:Calcium control of glycogen synthase activities in mouse diaphragms, rat adipocytes and rat hepatocytes. 642 46

Brief treatment of rat adipocytes with low concentration of trypsin activated both cell membrane and intracellular insulin-sensitive functions in marked contrast H2O2 (1), increase in pH, and oxidized glutathione (papers I and II). Glucose oxidation was activated maximally by trypsin in 30 s and preceded maximal activation of glycogen synthase, which occurred in 60s. Trypsin action to activate glycogen synthase was further enhanced by insulin. Mitochondrial pyruvate dehydrogenase was also rapidly activated by trypsin. With both insulin and trypsin action, mediator generation was directly demonstrated by glycogen synthase phosphoprotein phosphatase activation. Trypsin is thus the most insulin-like of these four agents studied since it acts by the formation of chemical mediator peptide(s) which are similar but not identical to those produced by insulin.
...
PMID:Independent control of selected insulin-sensitive cell membrane and intracellular functions-the linkage of cell membrane and intracellular events controlled by insulin. III. The influence of trypsin on cell membrane hexose transport and on glycogen synthase and mitochondrial pyruvate dehydrogenase activation. 679 3

Purified rat adipocyte plasma membranes incubated with insulin produce a soluble chemical mediator that stimulates pyruvate dehydrogenase when added to isolated mitochondria, or glycogen synthase when added to cell homogenates. The mediator appears to be a peptide and has been characterized by conventional chromatographic methods including gel filtration, ion exchange, and hydroxylapatite chromatography. These studies reveal that an insulin-dependent bioactive component, which is small and negatively charged at pH 7.4, can be eluted from Dowex 1 x 4 by 0.3-0.4 N NaCl or from hydroxylapatite by 0.05-0.15 M potassium phosphate. The mediator has also been partially purified by high-pressure liquid chromatography. A molecular sieving matrix produces a peak of insulin-dependent bioactivity that corresponds to a peak of absorbance at 210 nm (apparent Mr of 2000) and is increased by insulin. Reversed-phase high-pressure liquid chromatography indicates that the insulin-dependent bioactivity is of a hydrophilic nature. Previous studies showed that release of mediator from plasma membranes in response to insulin was blocked by inhibitors of serine proteases and esters of arginine. In addition, bioactivity of the insulin-treated plasma membrane supernatant could be destroyed by protease treatment. In the present experiments, pretreatment of intact adipocytes with serine protease inhibitors blocked the action of subsequently added insulin on several intracellular enzyme systems. These observations have been summarized in the following working model of one mode of insulin action. The binding of insulin to its receptor activates a membrane protease or alters an endogenous membrane substrate, resulting in the increased release into the cell of a small peptide fragment by proteolytic cleavage. The released peptide is proposed to modulate several cellular enzymes such as pyruvate dehydrogenase and glycogen synthase by interacting with phosphoprotein phosphatase or protein kinase activities, or both.
...
PMID:Production by plasma membranes of a chemical mediator of insulin action. 681 28

Hydroxymethylglutaryl CoA reductase catalyzes the limiting step in cholesterol synthesis in liver and other tissues. Beginning in 1973 studies with subcellular systems established that microsomal reductase is inactivated with ATP(Mg) and reductase kinase, and restored to full activity with phospho-protein phosphatase. By contrast reductase kinase is inactivated with phosphatase and reactivated with a second protein kinase (reductase kinase kinase). This bicyclic system has now been confirmed in terms of homogeneous enzyme components and by direct reversible phosphorylation with [gamma 32P]ATP in several laboratories. Short-term endocrine control of reductase and reductase kinase has been demonstrated in intact rat hepatocytes. Preincubation of cells with glucagon brought about a fall in the expressed activity of reductase and a rise in reductase kinase consistent with net phosphorylation of both enzymes. Total reductase levels were also severely depressed after glucagon. Addition of insulin to suspensions of hepatocytes had the reverse effect on expressed activity of reductase (elevated) and reductase kinase (depressed). Insulin also prevented the decay in total reductase activity. Since both protein kinases identified in this system are cAMP-insensitive, it was possible that hormonal signaling is mediated through the protein phosphatase that acts on both reductase kinase and reductase. In recent studies we have shown that the rate of activation of endogenous reductase in hepatocyte extracts (microsomes plus cytosol) is responsive to hormonal modulation. Pretreatment of hepatocytes with insulin increases apparent reductase phosphatase activity in extracts while glucagon diminishes the rate of reductase activation. HMG CoA is converted to mevalonate by the reductase enzyme. In hepatocytes mevalonate is rapidly converted to cholesterol and to a variety of isoprene derivatives. Expressed reductase activity falls precipitously when hepatocytes are incubated with mevalonate (added in the form of mevalono-lactone). As in the case with glucagon pretreatment reductase phosphatase is rapidly diminished. (Mevalonate itself is not inhibitory to reductase or reductase phosphatase activity in subcellular systems.) It is probable that a product of mevalonate metabolism generated in intact cells may act as a reductase phosphatase inhibitor. Among these added inorganic pyrophosphate inhibited reductase phosphatase at low concentrations.
...
PMID:Short-term regulation of hydroxymethylglutaryl coenzyme A reductase by reversible phosphorylation: modulation of reductase phosphatase in rat hepatocytes. 705 70

Immunotitrations of rat liver hydroxymethylglutaryl-CoA (HOMeGlt-CoA) reductase activity were performed before and after short-term changes in the nutritional or hormonal state of the animals. Changes in enzyme activity (increase or decrease) within 1 h following cholesterol feeding or glucagon or mevalonolactone administration to normal rats, or insulin administration to diabetic rats were accompanied by no change in the specific activity of the enzyme, as determined from the quantity of enzyme activity inactivated by a fixed quantity of antibody. These results support the conclusion that the loss in enzyme activity was due to conversion of the enzyme to immuno-unreactive products. In agreement with this conclusion the enzyme activity lost after these short-term physiological changes was not restorable by phosphoprotein phosphatase action. On the other hand, incubation of rat liver microsomes with ATP and Mg2+ decreased the specific activity of HOMeGlt-CoA reductase about tenfold, as determined by immunotitration. The low specific activity produced under these conditions was increased by phosphatase action to nearly the original level. The above evidence suggests that the changes in HOMeGlt-CoA reductase activity that resulted from short-term physiological changes in hormonal or nutritional states of an animal were brought about by a change in the quantity of enzyme, and not by reversible phosphorylation of pre-existing enzyme.
...
PMID:Regulation of short-term changes in hepatic beta-hydroxy-beta-methylglutaryl-CoA reductase activity. 711 48

Milk protein gene expression in mammary epithelial cells is regulated by the action of the lactogenic hormones insulin, glucocorticoids and prolactin. The mammary gland factor, MGF, has been shown to be a central mediator in the lactogenic hormone response. The DNA binding activity of MGF is hormonally regulated and essential for beta-casein promoter activity. We have used Red A Sepharose- and sequence-specific DNA affinity chromatography to purify MGF from mammary gland tissue of lactating sheep. Proteins of 84 and 92 kDa were obtained, proteolytically digested and the resulting peptides separated by reverse phase high pressure liquid chromatography. The 84 and 92 kDa proteins yielded very similar peptide patterns. The amino acid sequence of two peptides was determined. The sequence information was used to derive oligonucleotide probes. A cDNA library from the mRNA of mammary gland tissue of lactating sheep was screened and a molecular clone encoding MGF was isolated. MGF consists of 734 amino acids and has sequence homology with the 113 (Stat113) and 91 kDa (Stat91) components of ISGF3, transcription factors which are signal transducers of IFN-alpha/beta and IFN-gamma. Two species of MGF mRNA of 6.5 and 4.5 kb were detected in mammary gland tissue of lactating sheep. Lower mRNA expression was found in ovary, thymus, spleen, kidney, lung, muscle and the adrenal gland. MGF cDNA was incorporated into a eukaryotic expression vector and cotransfected with a vector encoding the long form of the prolactin receptor into COS cells. A strong MGF-specific bandshift was obtained with nuclear extracts of COS cells induced with prolactin. Treatment of activated MGF with a tyrosine-specific protein phosphatase resulted in the loss of DNA binding activity. Prolactin-dependent transactivation of a beta-casein promoter-luciferase reporter gene construct was observed in transfected cells.
...
PMID:Mammary gland factor (MGF) is a novel member of the cytokine regulated transcription factor gene family and confers the prolactin response. 788 87

In this study, we examined the role of insulin, protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) cascade in activation of protein phosphatase-1 (PP-1) by using three complementary approaches. First, differentiated L6 cells were acutely exposed to 12-O-tetradecanoylphorbol-13-acetate (TPA, 400 nM) to activate PKC. In these cells, TPA caused 32% stimulation of PP-1 activity. The PP-1 stimulation by TPA was comparable to stimulation by insulin (t1/2 = 1 min and EC50 = 5 nM) with a maximum effect in 5 min. The effects of insulin and TPA were not additive. Insulin and TPA also stimulated MAPK (> 2-fold increase over basal, with myelin basic protein as a substrate). ML-9, a myosin light chain kinase inhibitor, blocked the effects of insulin and TPA on both MAPK and PP-1 activation. In the second approach, PKC was down-regulated by chronic treatment with TPA. In these cells subsequent effects of insulin on MAPK and PP-1 activation were blocked, without an effect on basal enzyme levels. In the third approach, two selective inhibitors of PKC, calphostin and chelerythrine chloride, were used to inhibit PKC. These inhibitors completely prevented insulin and TPA stimulation of MAPK and PP-1 and blocked insulin-induced translocation of PKC to the plasma membranes. We conclude that PKC plays an important role in insulin stimulation of PP-1 via the activation of MAPK cascade.
...
PMID:Stimulation of protein phosphatase-1 activity by phorbol esters. Evaluation of the regulatory role of protein kinase C in insulin action. 751 82


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---