Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nuclear envelopes are associated with a protein phosphokinase and a phosphoprotein phosphatase, whose activities are modulated by poly(A) in an opposite manner. The activities of these enzymes were determined in nuclear ghosts from liver and oviduct of quails of different age and of different hormone status. Under optimal conditions, kinase activity was found to increase in immature animals 8-fold in response to diethylstilbestrol; co-administration of progesterone had no marked effect on enzyme activity. After the initial burst, the activity of the enzyme increased only slightly during ageing. Two proteins present in nuclear ghosts of Mr 64 000 and of Mr 106 000 are phosphorylated during the kinase reaction; both the relative and the absolute extents of phosphate incorporation into these proteins alter drastically during ageing or hormone treatment of immature animals. Like the kinase activity, the activity of protein phosphatase increased in immature animals markedly in response to hormone treatment. Thereafter the activity remained constant in liver while in oviducts the phosphatase activity dropped to 30% in both mature and old animals.
Mech Ageing Dev 1984 Sep
PMID:Age-dependent changes of nuclear envelope protein phosphokinase and protein phosphatase activities. Significance for altered nucleo-cytoplasmic mRNA translocation during development. 609 91

Acetyl-CoA carboxylase has been purified from lactating rat mammary gland using a combination of ammonium sulphate and poly(ethyleneglycol) precipitations. The enzyme was purified from 35--70-fold with a yield of over 50%, the exact figures being difficult to estimate because of activation of the enzyme that occurs during the preparation. The preparation was homogeneous by the criterion of polyacrylamide gel electrophoresis in sodium dodecyl sulphate and had a single subunit of molecular weight 240,000, containing 1.02 +/- 0.04 molecules of biotin and 3.1 +/- 1.7 molecules of alkali-labile phosphate per subunit. The purified enzyme was phosphorylated and inactivated rapidly when incubated in the presence of [gamma 32P]ATP and magnesium ions with the purified catalytic subunit of cyclic-AMP-dependent protein kinase from rabbit skeletal muscle. Both phosphorylation and inactivation are blocked by the heat-stable protein inhibitor of cyclic-AMP-dependent protein kinase, and can be reversed by incubation with purified protein phosphatase-1 from rabbit skeletal muscle. The inactivation by the protein kinase and reactivation by the protein phosphatase correlate with the near-stoichiometric phosphorylation and dephosphorylation of site(s) located in a single tryptic peptide. Phosphorylation does not affect the Km for substrates, but brings about a twofold decrease in V and a twofold increase in the apparent dissociation constant for the allosteric activator, citrate. We also present evidence that the activation of rabbit mammary acetyl-CoA carboxylase by protein phosphatase-1 described previously [Hardie and Cohen (1979) FEBS Lett. 103, 333-338] is due to dephosphorylation at site(s) which are not phosphorylated by either cyclic-AMP-dependent protein kinase or acetyl-CoA carboxylase kinase-2. These results suggest that the rapid inactivation of acetyl-CoA carboxylase, and hence fatty acid synthesis, by adrenaline in adipose tissue, or glucagon in the liver, is due to phosphorylation of the enzyme by cyclic-AMP-dependent protein kinase.
Eur J Biochem 1980 Sep
PMID:Reversible phosphorylation and inactivation of acetyl-CoA carboxylase from lactating rat mammary gland by cyclic AMP-dependent protein kinase. 610 9

Studies were made on the dephosphorylation and activation of chicken liver acetyl-coenzyme-A carboxylase. The enzyme isolated by avidin-Sepharose affinity chromatography in the presence of protein phosphatase inhibitors contained 4.9 +/- 0.2 mol of alkali-labile phosphate/mol subunit and had a specific activity of 3.5 +/- 0.4 units/mg protein. The purified enzyme was dephosphorylated and activated concomitantly when incubated in the presence of protein phosphatase with a release of approximately 2 mol of phosphate/mol subunit. Limited tryptic digestion of the native and dephosphorylated forms of the enzyme (Mr 220 000) containing 4.9 and 2.9 mol of phosphate/mol of subunit, respectively, gave almost quantitatively similar polypeptides of Mr 215 000 containing 4.0 mol and 3.0 mol of phosphate per mol, respectively, which were indistinguishable by dodecylsulfate-polyacrylamide gel electrophoresis. A peptide of Mr approximately 5000 was lost from both enzymes. This result suggests that at least one of the two protein-phosphatase-labile phosphorylation sites is sensitive to trypsin. The native enzyme and those modified by protein phosphatase or by limited tryptic digestion exhibited a bi-phasic dependence on citrate. Activation of the native enzyme by protein phosphatase occurred at all the concentrations of citrate used. However, activation of the enzyme by limited tryptic digestion was found at concentrations greater than 5 mM citrate. The dephosphorylation by protein phosphatase caused an approximately fivefold activation in the enzyme activity when assayed at physiological concentrations of citrate (0.5-2.0 mM).
Eur J Biochem 1983 Sep 01
PMID:Dephosphorylation and activation of chicken liver acetyl-coenzyme-A carboxylase. 613 6

In polymorphonuclear leukocytes from severely diabetic patients the rate of glycolysis is decreased due to decreased activity of phosphofructokinase, and the glycogen content and rate of glycogen synthesis are decreased due to a decreased total activity of glycogen synthase and an impaired activation of this enzyme. Covalent modification of glycogen synthase by phosphorylation creates a continuum of phosphorylated enzyme forms of decreasing activity. Phosphorylation of a single peptide, whether by the synthase kinase or the cyclic AMP dependent protein kinase, is critical for the associated kinetic changes during the initial phosphorylation. Conversely, dephosphorylation of this particular peptide is associated with complete activation. The protein phosphatase activity of the microsomal fraction may be separated into functionally and possibly also structurally different phosphorylase- and synthase-phosphatase activities, where the latter appears to be dependent on free cytoplasmic Ca2+. It is hypothesized that it is synthase-phosphatase activity that is absent in leukocytes from diabetic patients and is restored upon insulin treatment.
J Clin Chem Clin Biochem 1983 Sep
PMID:The polymorphonuclear leukocyte in diabetes mellitus. 622 61

Pig heart phosphoprotein phosphatase [phosphoprotein phosphophydrolase, EC 3.1.3.16] of Mr 224,000 was dissociated by gel-filtration on Sephacryl S-300, into an active subunit (alpha subunit) of Mr 31,000 and inactive subunits of higher molecular weight in the presence of 6 M urea. After the removal of urea, these subunits reassociated, forming two enzyme forms of Mr 237,000 (Form 1) and Mr 123,000 (Form 2). Form 2 was produced by association of the alpha subunit with an inactive subunit (beta subunit) of Mr 80,000, while Form 1 was formed by combination of the alpha subunit with a complex of inactive subunits which was eluted from a Sephadex G-150 column in fractions of molecular weight range greater than 80,000. The dissociation and reassociation of the subunits of Form 1 by the same urea method produced not only Form 1, but also significant amounts of Form 2, indicating that the inactive subunits of Form 1 were a complex of the beta subunit with another inactive subunit(s). The molecular parameters and other properties of Form 1 were very close to those of the original enzyme. By the conversion of Form 1 to Form 2, the activities of Form 1 towards phosphorylase a and glycogen synthetase b were enhanced 2-3 fold with no significant change in activity towards P-H1 histone or in response to the stimulatory effect of Mg(CH3COO)2 on the dephosphorylation of P-H2B histone. However, removal of the beta subunit from From 2 resulted in strong suppression of activity towards P-H1 histone and response to the salt effect with lesser effects on the activities of Form 2 towards phosphorylase a and glycogen synthase b.
J Biochem 1981 Sep
PMID:Reconstitution of urea-dissociated subunits of a pig heart phosphoprotein phosphatase. 627 90

A protein kinase active on fructose-bisphosphatase (D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11) was demonstrated in rat liver cell sap. The protein kinase activity was stimulated by cyclic AMP and coincided with the activity of cyclic AMP-dependent protein kinase type I. In addition, three different peaks of phosphoprotein phosphatase active on [32P] phosphofructose-bisphosphatase were found on chromatography of rat liver cell sap on a DEAE-cellulose column. These phosphatases needed divalent cations for full activity. 5'-AMP, a negative modulator of fructose-bisphosphatase, had no effect on the phosphorylation-de-phosphorylation reactions of the enzyme. ATP and Ca2+ did not influence the dephosphorylation reaction of fructose-bisphosphatase.
Biochim Biophys Acta 1982 Sep 07
PMID:The demonstration in rat liver cell sap of protein kinase and phosphoprotein phosphatase active on fructose-bisphosphatase. 628 6

A Ca2+-dependent, calmodulin-stimulated protein phosphatase (EC 3.1.3.16) is known to be associated with calcineurin, a major calmodulin binding protein in brain. The protein phosphatase activity has now been shown to be retained by a substrate affinity column (thiophosphorylated myosin P-light chain Sepharose) in the presence of Ca2+, and to be eluted specifically with EGTA. Calcineurin behaved identically. This establishes that calcineurin is the Ca2+-dependent protein phosphatase, and that interaction of Ca2+ with the B-subunit is essential for substrate binding.
Biochim Biophys Acta 1983 Sep 14
PMID:Calcineurin is a calcium ion-dependent, calmodulin-stimulated protein phosphatase. 630 41

More than 97% of spectrin phosphatase activity in human erythrocyte hemolysate was recovered in cytosol. The cytosolic phosphatase activity was resolved into four peaks, namely phosphatases I (22%, Mr = 180,000), II (3%, Mr = 42,000), III (8%, Mr = 177,000), and IV (62%, Mr = 104,000), by aminohexyl-Sepharose column chromatography. Although these phosphoprotein phosphatases also catalyzed the dephosphorylation of phosphorylase a, glycogen synthase b, and phosphorylated H1 and H2B histones, the phosphatases differed from each other in preferences for substrates and the Mg2+ or Mn2+ requirements for their activities. The treatment with 80% ethanol converted phosphatases I, III, and IV to Mr = 31,000 forms which had essentially the same physical and catalytic properties. By contrast, the molecular weight and catalytic properties of phosphatase II, which was Mg2+- or Mn2+-dependent, were not changed by the same ethanol treatment. The major spectrin phosphatase, phosphatase IV, was purified to near homogeneity, as judged by polyacrylamide gel electrophoresis. Sodium dodecyl sulfate-gel electrophoresis revealed that the enzyme was composed of one 32,000-Da polypeptide (alpha) and one 69,000-Da polypeptide (beta). Km values of the enzyme for phosphorylated spectrin and H2B histone were 1.63 +/- 0.45 and 48.2 +/- 7.6 microM, respectively. The spectrin phosphatase activity was stimulated about 2-fold by 5-25 mM Mg2+, but was completely inhibited by the same concentration of Mn2+. Physiological concentrations of adenine nucleotides, 2,3-diphosphoglyceric acid, cyclic nucleotides, or Ca2+ and/or calmodulin had no significant effect on the reaction, but 20 mg/ml of hemoglobin inhibited the reaction by 60%. -SH-blocking agents but not iodoacetate inhibited the reaction.
J Biol Chem 1983 Sep 10
PMID:Phosphoprotein phosphatases in human erythrocyte cytosol. 630 5

The major active protein phosphatase present in a rabbit skeletal muscle extract is associated with the glycogen particle and migrates in sucrose density gradient centrifugation as a Mr = 70,000 protein and contains modulator activity. Addition of extra modulator protein causes a time- and concentration-dependent conversion of the enzyme to an inactive FA-ATP, Mg-dependent form. The intrinsic modulator in the active phosphatase is destroyed by limited proteolysis without an appreciable change in the phosphatase activity. The proteolyzed active enzyme has a lower molecular weight (Mr = 40,000) and it reassociates with the modulator producing a FA-ATP, Mg-dependent enzyme form (Mr = 60,000). The modulator protein is used stoichiometrically in the activation of the ATP, Mg-dependent phosphatase. This is in agreement with the presence of one unit of modulator activity per unit of native spontaneously active phosphatase.
Biochem Biophys Res Commun 1983 Sep 30
PMID:Role of the modulator protein in the interconversion of rabbit skeletal muscle protein phosphatase. 631

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.
Endocrinology 1983 Sep
PMID:Regulation of hepatic glycogen metabolism in pre- and postnatal rats. 640 92


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