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

The regional and cellular distribution of G-substrate, a 23,000-dalton protein substrate specific for guanosine 3',5'-cyclic monophosphate-dependent protein kinase, has been examined in mammalian brain using immunoprecipitation, radioimmunoassay, and peptide-mapping techniques. In rabbit brain, G-substrate was found to be highly concentrated in the cerebellum. The concentration of G-substrate in cerebellar cytosol was 27.2 pmol/mg. The concentrations of G-substrate in cortex, hippocampus, and caudate were only 1 to 2% of that found in cerebellum. Studies of neurological mutant mice lacking either Purkinje cells (PCD and nervous) or granule cells (weaver) suggested that, within the cerebellum, G-substrate is localized almost exclusively in Purkinje cells. A phosphoprotein present in noncerebellar brain regions, which co-migrated with G-substrate on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was shown by peptide mapping to consist predominantly of phosphatase inhibitor-1. Phosphatase inhibitor-1, a potent inhibitor of protein phosphatase-1, is known to share several physicochemical properties with G-substrate. In contrast to the results obtained with G-substrate, the concentration of phosphatase inhibitor-1 was significantly lower in cerebellum than in other major brain regions. These and other data suggest that G-substrate may be a Purkinje cell-specific protein phosphatase inhibitor.
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PMID:Localization in mammalian brain of G-substrate, a specific substrate for guanosine 3',5'-cyclic monophosphate-dependent protein kinase. 609 45

The need for nonshivering heat production, a principal function of brown adipose tissue, is accentuated in neonates. Accordingly, brown fat in the rat exhibits a very pronounced process of morphological and functional maturation perinatally, reaches a peak in its differentiation and heat-generating capacity within 1-2 weeks after birth, and undergoes involutive changes later in life. The later process of dedifferentiation can be either prevented or reversed by exposing the animals to cold ambient temperature for a prolonged period of time (cold acclimatization). The regulation of both the tissue maturation processes and the superimposed acute heat production are hormone mediated. Thus, the hormone receptor system within the adipocyte membrane and the sequence of molecular events interconnecting the initial hormonal stimulus with its final intracellular effect(s) are of considerable importance. The brown adipocytes of developing rats possess adrenoreceptors that can be pharmacologically classified as beta 1 (linked to adenylate cyclase) and alpha 2 (possibly linked to guanylate cyclase), multiple forms of cyclic nucleotide dependent and independent protein kinases, a protein kinase inhibitor, and at least two distinct phosphoprotein phosphatases associated with three phosphoprotein phosphatase modulators. The characteristics and developmental alterations of these regulatory components were studied in considerable detail by our group during the past decade. The results uncovered several target systems for ontogenic modifications of hormonal responses. Strong support was obtained for the hypothesis that protein phosphorylation and dephosphorylation is a major molecular mechanism involved in the regulation of both the brown adipocyte function and its proliferative activity during ontogenic development.
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PMID:Mechanisms of hormonal regulations in brown adipose tissue of developing rats. 614 37

Preincubation of two homogeneous rabbit liver phosphoprotein phosphatases (phosphophoprotein phosphohydrolases, EC 3.1.3.16) (Khandelwal, R.L., Vandenheede, J.R. and Krebs, E.G. (1976) J. Biol. Chem. 251, 4850-4858) with ATP, ADP and PPi caused a time- and concentration-dependent inactivation of the enzyme activity. A 50% inactivation of phosphoprotein phosphatase I required relatively low concentration of inactivating metabolite and less preincubation time as compared to the inactivation of phosphoprotein phosphatase II. AMP, adenosine, adenine, Pi, EDTA, EGTA, 1,10-phenanthroline and diethyl dithiocarbamate were without effect on both enzymes. Pretreatment of both enzymes by metal-chelating agents followed by PPi did not augment the effect observed with PPi alone. Both inactivated enzymes could be reactivated by cobalt or manganese in the presence of dithiothreitol. Although the extent of reactivation by these two metal ions was almost similar, cobalt required a ten times lower concentration than manganese for this process. No difference in inactivation or reactivation of both enzymes was observed with different substrates, phosphorylase a, histone or casein, employed in the assay. Pi and PPi added during the assay inhibited activities of both phosphatases with phosphorylase a and casein substrates. With histone as substrate, PPi slightly inhibited enzyme activities at lower concentrations (0.01-0.25 mM) but activated at higher concentrations. Pi activated both enzymes with this substrate; maximal activation being observed at a concentration of 5 mM.
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PMID:Studies on in activation and reactivation of homogeneous rabbit liver phosphoprotein phosphatases by inorganic pyorphosphate and divalent cations. 624 57

The diverse metal requirements for activity of the phosphoprotein phosphatases (EC 3.1.3.16) concerned with glycogen metabolism in rat liver were postulated to reflect the diverse binding intensities of their essential metal(s). After inactivation by fluoride, three of these phosphatases had similar metal requirements in contrast to a fourth phosphatase. Further similarities led to a grouping of these enzymes into two general types. Phosphatases designated type 1 consisted of three enzymes which had the following properties; (1) preference for glycogen phosphorylase a as a substrate; (2) molecular weights in excess of 100 000; (3) conversion to an active 30 000 dalton 'subunit' form upon selective denaturation by 80% ethanol; (4) diverse degrees of stimulation by metals (Mg2+ and Mn2+); and (5) changes to an absolute dependence upon added Mn2+ (but not Mg2+) for activity of both the holoenzyme and the subunit after a demetallating treatment with fluoride in EDTA. The phosphatase designated type 2 exhibited the following properties; (1) preference for glycogen synthase D as a substrate; (2) molecular weight of 50 000; (3) no conversion to an active 30 000 dalton subunit form upon selective denaturation by 80% ethanol; (4) complete metal-dependence upon either Mg2+ or Mn2+; and (5) no change to an absolute dependence on added Mn2+ for activity after a demetallating treatment with fluoride in EDTA.
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PMID:Use of fluoride to inactivate phosphorylase a phosphatases from rat liver cytosol. Presence of fluoride-insensitive glycogen synthase-specific phosphatase. 625 Jun 27

The substrate specificity of a preparation of phosphoprotein phosphatase (Mr = 32 000) from rat liver was investigated. Phosphopeptides based on the structure Leu-Arg-Arg-Ala-Ser(P)-Val-Ala-Glx-Leu and Ala-Arg-Thr-Lys-Arg-Ser-Gly-Ser(P)-Val-Tyr-Glu-Pro-Leu-Lys were used. These phosphopeptides correspond to the phosphorylation sites of rat liver pyruvate kinase (type L) and the beta subunit of rabbit muscle phosphorylase b kinase, respectively. A decrease in the apparent Km values and a concomitant increase in Vmax values was observed when the number of amino acyl residues after the phosphoseryl residue in the respective phosphopeptides were increased from 2 to 4, 5, or 6. Most of the phosphopeptides investigated generally showed apparent Km values higher than the values obtained with phosphopyruvate kinase. Ala-Ser(P)-Val-Ala and Gly-Ser(P)-Val-Tyr appeared to be the shortest phosphopeptides that could be dephosphorylated rapidly. These findings support the hypothesis that a small part of the phosphoprotein may be sufficient to fulfill the minimal requirements for its dephosphorylation.
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PMID:Phosphopeptide substrates of a phosphoprotein phosphatase from rat liver. 625 66

When the crude phosphoprotein phosphatase fraction of rat liver cytosol was treated with 80% aqueous ethanol at room temperature, the activity with phosphorylase alpha as substrate was increased by 110%, but those with glycogen synthase D and phosphohistone were decreased by 53 and 34%, respectively. Chromatography of the ethanol-treated fraction on DE-52 revealed that while phosphoprotein phosphatase IA (Mr=69,000) remained to exist even though it was reduced, phosphatases IB (Mr=-300,00) and II (Mr=160,000) were totally replaced by a new phosphatase form with an approximate molecular weight of 35,000. This low molecular weight form has been designated phosphatase III. When partially purified phosphatases IB and II were separately treated with ethanol, they were converted to phosphatase III. These results suggest that phosphoprotein phosphatases IB and II, but IA, contain phosphatase III as a subunit. Phosphatases IB and II, however, must differ in structure since "IB to III" is accompanied by an increase in phosphorylase phosphatase activity much greater than that for "II to III"
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PMID:Effect of ethanol treatment on high molecular weight phosphoprotein phosphatases of rat liver. 625 66

The phosphoprotein phosphatase activity of a commercial preparation of bovine intestinal alkaline phosphatase (EC 3.1.3.1) was examined using phosvitin and dentine phosphoprotein as substrates. Over 90% and 70% of the phosphorus from dentine phosphoprotein and phosvitin were hydrolyzed in 2 h. The optimum pH of the enzyme for the dephosphorylation of phosvitin and dentine phosphoprotein was nearly 6. No protein phosphatase activity was observed when the alkaline phosphatases from bovine liver and pulp were investigated.
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PMID:Phosphoprotein phosphatase activity of bovine intestinal alkaline phosphatase. 626 66

Under certain physiological conditions a change in the phosphorylation of histones in mouse epidermis in vivo was observed. Thus a single local application of the tumor-promoting mitogen 12-O-tetradecanoylphorbol-13-acetate caused a long-lasting increase of histone H1 phosphorylation which paralleled stimulated cell proliferation. Injection of the antimitotic beta-adrenergic agonist isoproterenol led to a temporary decrease in the rate of phosphorylation of H1, H2A and H2B immediately after cyclic AMP accumulation. A complete protein phosphorylation system could be demonstrated in mouse epidermis homogenates. The following enzyme activities were partially purified and characterized: a cyclic AMP-dependent histone kinase; a 'casein kinase' and an 'unspecific' protein kinase; a histone-specific protein phosphatase; and two 'unspecific' phosphoprotein phosphatases. In addition, a stimulatory effect of cyclic GMP on histone phosphorylation was observed. The enzymes were found to be predominantly localized in the 105000 X g supernatant, but a small proportion of protein kinase and phosphatase activity could be regularly demonstrated in cell nuclei.
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PMID:Histone phosphorylation in phorbol ester stimulated and beta-adrenergically stimulated mouse epidermis in vivo and characterization of an epidermal protein phosphorylation system. 626 86

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.
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PMID:Reconstitution of urea-dissociated subunits of a pig heart phosphoprotein phosphatase. 627 90

Protein synthesis initiation in reticulocyte lysates is inhibited by low concentrations (1-20 ng/ml) of double-stranded RNA (ds RNA) due to the activation of a ds RNA-dependent cAMP-independent protein kinase (ds I) that phosphorylates the alpha subunit of the eukaryotic initiation factor eIF-2. In lysates, ds I is present in the latent inactive form and is associated with the ribosome complement. Latent ds I is solubilized by extraction with high-salt buffers and can be purified in its latent form. Activation of purified latent ds I requires ds RNA and ATP and is accompanied by the ds RNA-dependent autophosphorylation of a polypeptide doublet of 70,000 and 72,000 daltons ("70k/72k"), which represent different phosphorylated states of the same polypeptide. These are phosphorylated in the sequence 70k-->72k; increased phosphorylation of 72k is associated with increased ds I activation. Lysates (or Sepharose 6B ribosomes) treated with ds RNA display a similar ds I phosphoprotein profile, and this is accompanied by the phosphorylation of endogenous eIF-2alpha (38,000 daltons). Delayed (32)P pulses in ds RNA-inhibited lysates indicate that the phosphates on ds I and eIF-2alpha turn over. Under defined conditions, activated ds I in lysates is selectively dephosphorylated by endogenous protein phosphatase(s), and this is accompanied by the dephosphorylation of eIF-2alpha. Similarly, purified activated ds I is rapidly dephosphorylated by unfractionated lysate protein phosphatase(s) and by type 2 protein phosphatase but not by type 1 protein phosphatase. The dephosphorylation of ds I occurs in the sequence 72k-->70k and is correlated with ds I inactivation. The heat-stable protein phosphatase inhibitor-2, which selectively blocks type 1 protein phosphatase, does not significantly affect the dephosphorylation of ds I by type 2 protein phosphatase or by unfractionated lysate phosphatases. The data support the conclusion that a ds I phosphatase activity with type 2 characteristics is involved in the regulation of ds I activity.
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PMID:Regulation of double-stranded RNA-activated eukaryotic initiation factor 2 alpha kinase by type 2 protein phosphatase in reticulocyte lysates. 629 6


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