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)

We have detected a protein phosphatase activity in soluble extracts from the halophilic archaeon Haloferax volcanii. This activity was markedly stimulated by the divalent metal ions Mn2+ and Cd2+. It dephosphorylated phosphoseryl residues in casein, mixed histones, and phosphorylase a, but not phosphotyrosyl residues in reduced, carboxyamidomethylated and maleylated lysozyme. This protein phosphatase activity was inhibited by NaF, Zn2+, vanadate, molybdate, inorganic phosphate, inorganic pyrophosphate, or p-nitrophenyl phosphate, or by treatment with diethylpyrocarbonate. Activity was unaffected by other potential inhibitors or activators such as polyamines, heparin, cyclic nucleotides, Ca2+/calmodulin, tartrate, tetramisole, okadaic acid, microcystin LR, or sulfhydryl-modifying agents. The functional similarities between this protein-serine phosphatase and that previously identified in another archaeon, the extreme acidothermophile Sulfolobus solfataricus, suggest the existence of a family of divalent metal ion-stimulated protein-serine phosphatases of extremely ancient origin in the Archaea.
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PMID:A protein-serine phosphatase from the halophilic archaeon Haloferax volcanii. 839 5

Okadaic acid, penetrating the human erythrocytes, almost completely inhibits P-Ser-protein phosphatase activity, whereas it unaffects Ser/Thr-protein kinase activity (casein kinases CKI and CKII), thus promoting a marked increase of the endogenous Ser-phosphorylation level of membrane proteins, such as cytoskeletal spectrin beta-subunit (band 2) and transmembrane band 3 protein. By contrast, the Tyr-phosphorylation state of band 3 protein is practically unaffected by okadaic acid, being unaffected both Tyr-protein kinase and P-Tyr-protein phosphatase activities.
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PMID:Effect of okadaic acid on membrane protein phosphorylation in human erythrocytes. 839 24

The substrate specificity of the cyanobacterial dual-specificity protein phosphatase, IphP, was explored using a variety of potential substrates. The enzyme displayed phosphomonoesterase activity toward a broad range of peptide, protein, and low molecular weight organophosphate compounds. It displayed little or no hydrolase activity toward phosphodiesters, phosphoramides, carboxyl esters, or sulfoesters. However, it did display measurable pyrophosphatase activity, especially toward ADP and ATP. Among the low molecular weight phosphomonoesters, the presence of an aromatic ring either as part of the leaving group alcohol or immediately adjacent thereto, as in 5'-AMP, was a strong positive determinant for hydrolysis. Among peptide and protein substrates, a rough, but imperfect, correlation between charge character and hydrolysis was noted in which proteins and phosphorylation sites of an acidic nature seemed favored. Heparin affected IphP activity in a substrate-dependent manner. Toward small organophosphates, heparin had no significant effect, but it was inhibitory toward most protein and peptide substrates. However, toward phosphoseryl casein and MAP kinase, it enhanced activity as much as 10-fold. This enhancement was attributed to the ability of heparin to bind to these substrate proteins, as well as IphP, and recruit them to the same microenvironment.
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PMID:Substrate specificity of IphP, a cyanobacterial dual-specificity protein phosphatase with MAP kinase phosphatase activity. 865 37

The protein phosphatase encoded by coliphage lambda (PPlambda) was found to be the equivalent of the minimal catalytic core of serine/threonine protein phosphatases (PP) by biochemical and mutational criteria. Bacterially expressed truncated versions of PP1 and PP5 phosphatases, representing the catalytic cores homologous to PPlambda, exhibited potent phosphatase activity. Unlike full-length PP1, but like PPlambda, the recombinant cores could use casein, p-nitrophenyl phosphate, and a wide variety of peptides as substrates and were resistant to okadaic acid, microcystin-LR, and trypsin. Mutations of His173, Asp208, or Arg221 had little effect on the activity of the PP1 core protein, indicating its closer identity with PPlambda than with full-length PP1. Terminal deletions of a few amino acids of the cores destroyed their activity, supporting their minimal nature. Analysis of PPlambda mutants suggested an influence of the substrate on metal ion binding. The minimal length of a phosphopeptide substrate of PPlambda appeared to be a phosphorylated serine/threonine flanked by 1 or 2 amino acid residues on either side, the N-terminal ones being more effective.
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PMID:Interactions between a minimal protein serine/threonine phosphatase and its phosphopeptide substrate sequence. 879 96

Protein phosphorylation in a low speed supernatant of human peripheral nerve (tibial and sural) homogenate was investigated. The major phosphorylated proteins had molecular mass in the range of 70, 55, 45, and 25 kDa. Mg2+ or Mn2+ was essential for maximum phosphorylation although Zn2+, Co2+, and Ca2+ could partially support phosphorylation. External protein substrates casein and histone were also phosphorylated. The protein phosphatase inhibitor orthovanadate enhanced the phosphorylation of the 45 and 25 kDa proteins significantly. Concanavalin A-Sepharose chromatography of the phosphorylated peripheral nerve proteins showed that the 25 kDa protein was a glycoprotein. Protein phosphorylation of peripheral nerves from leprosy affected individuals was compared with normals. The phosphorylation of 25 kDa protein was decreased in most of the patients with leprosy.
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PMID:Protein phosphorylation in human peripheral nerve: altered phosphorylation of a 25-kDa glycoprotein in leprosy. 882 44

The major spontaneously active serine/threonine (Ser/Thr) protein phosphatase activities in N. crassa wild type (FGSC 424) were type-1 (PP1), type-2A (PP2A) and type-2C (PP2C). PP1 and PP2C predominantly dephosphorylated phosphorylase a and casein, respectively. PP2A acted on both substrates, but was two-fold more active against casein. PP1 activity was inhibited by protamine, heparin, okadaic acid (IC50 50 nM) and mammalian inhibitor-1 (IC50 2 nM). On the other hand. PP2A activity was inhibited by much lower concentrations of okadaic acid (IC50 0.2 nM) and also by protamine, but not by heparin or inhibitor-1. About 80% of total PP1 activity was associated with the particulate fraction and could be partially extracted with 0.5 M NaCl. Seventy and ninety percent of PP2A and PP2C activities, respectively, were found in the soluble fraction. In addition we have partially purified an acid and thermostable PP1 inhibitor which effectively inhibits both N. crassa and mammalian PP1.
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PMID:Serine/threonine protein phosphatases and a protein phosphatase 1 inhibitor from Neurospora crassa. 903 9

This is the first identification of a Ca2+-inhibitable casein kinase (CPK) which we have isolated from the 100000 x g supernatant of Paramecium cell homogenates. The 1000-fold enriched CPK activity depends on millimolar Mg2+ and is inhibited by low concentrations of heparin or by > or = 100 microM Ca2+. Enzyme activity is stimulated by polylysine or polyarginine with either casein or with specific casein kinase-2 (CK-2) peptide substrates (RRRDDDSDDD and RREEETEEE). The enzymic properties are similar with GTP instead of ATP. CPK does not undergo autophosphorylation. In gel kinase assays, enzyme activity is associated with a 36 kDa band. Calmodulin as another characteristic substrate for mammalian CK-2 has not been phosphorylated by this protein kinase. Besides casein, CPK phosphorylates in vitro the catalytic subunit of bovine brain calcineurin (CaN), a typical substrate of type 1 mammalian casein kinase (CK-1) in vitro. Again this phosphorylation is significantly reduced by Ca2+. Thus, CPK combines aspects of different casein kinases, but it is clearly different from any type known by its Ca2+ inhibition. Since CPK also phosphorylates the exocytosis-sensitive phosphoprotein, PP63, in Paramecium, which is known to be dephosphorylated by CaN, an antagonistic Ca2+-effect during phosphorylation/dephosphorylation cycles may be relevant for exocytosis regulation.
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PMID:A novel, calcium-inhibitable casein kinase in Paramecium cells. 903 1

Non-metabolized glucose derivatives may cause inactivation of phosphorylase but, unlike glucose, they are unable to elicit activation of glycogen synthase in isolated hepatocytes. We report here that, after the previous inactivation of phosphorylase by one of these glucose derivatives (2-deoxy-2-fluoro-alpha-glucosyl fluoride), glycogen synthase was progressively activated by addition of increasing concentrations of glucose. Under these conditions, the degree of activation of glycogen synthase was linearly correlated with the intracellular glucose-6-phosphate (Glc-6-P) concentration. Addition of glucosamine, an inhibitor of glucokinase, decreased both parameters in parallel. Further experiments using an inhibitor of either protein kinases (5-iodotubercidin) or protein phosphatases (microcystin) in isolated hepatocytes indicated that Glc-6-P does not affect glycogen-synthase kinase activity but enhances the glycogen-synthase phosphatase reaction. Experiments in vitro showed that the synthase phosphatase activity of glycogen-bound type-1 protein phosphatase was increased by physiological concentrations of Glc-6-P (0.1-0.5 mM), but not by 2.5 mM fructose-6-P, fructose-1-P or glucose-1-P. At physiological ionic strength, the glycogen-associated synthase phosphatase activity was nearly entirely Glc-6-P-dependent, but Glc-6-P did not relieve the strong inhibitory effect of phosphorylase a. The large stimulatory effects of 2.5 mM Glc-6-P, with glycogen synthase b and phosphorylase a as substrates, appeared to be mostly substrate-directed, while the modest effects observed with casein and histone IIA pointed to an additional stimulation of glycogen-bound protein phosphatase-1 by Glc-6-P. We conclude that glucose elicits hepatic synthase phosphatase activity both by removal of the inhibitor, phosphorylase a, and by generation of the stimulator, Glc-6-P.
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PMID:Glucose-induced glycogenesis in the liver involves the glucose-6-phosphate-dependent dephosphorylation of glycogen synthase. 914 44

The molecular mechanisms whereby calcium stimulates secretion are uncertain. In the present study, we used streptolysin O (SLO)-permeabilized chief cells from guinea pig stomach to investigate whether protein phosphatase-2B (calcineurin), a calcium/calmodulin-dependent, serine/threonine phosphatase plays a role in mediating calcium-induced pepsinogen secretion. Preincubation of cells with alpha-naphthylphosphate, a non-specific phosphatase inhibitor, decreased calcium-induced secretion. Likewise, specific inhibitors of protein phosphatase-2B (cyclosporin-A and FK-506) caused a dose-dependent reduction in calcium-induced pepsinogen secretion. Moreover, in intact cells, cyclosporin-A and FK-506 inhibited pepsinogen secretion caused by cholecystokinin, carbamylcholine and A23187, agonists known to increase chief cell cytosolic calcium. Okadaic acid, an inhibitor of protein phosphatase-1 and -2A, had no effect on secretion caused by these agonists. Chief cell calcium-dependent phosphatase activity, measured using radiolabeled casein as substrate, was reduced selectively by inhibitors of protein phosphatase-2B. Endogenous substrates for calcium/calmodulin-dependent phosphatase activity were identified by analyzing chief cell lysates using 2-dimensional gel electrophoresis. Increasing the cytosolic calcium concentration resulted in dephosphorylation of a 55-kDa, acidic cytoskeletal protein. FK-506 inhibited dephosphorylation of this protein. Thus, in permeabilized chief cells, specific inhibitors of protein phosphatase-2B inhibit calcium-induced pepsinogen secretion, calcium/calmodulin-dependent phosphatase activity and calcium-induced dephosphorylation of a 55-kDa, acidic cytoskeletal protein. These results support the hypothesis that protein phosphatase-2B (calcineurin) plays an important role in mediating calcium-induced exocytosis.
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PMID:Regulation of calcium-induced exocytosis from gastric chief cells by protein phosphatase-2B (calcineurin). 920 77

Intracellular protein phosphatase activity has been identified in the yeast Yarrowia lipolytica. This activity was maximal early in its exponential growth phase, and it was enhanced by Pi-deficiency of the culture medium. On a Pi-deficient medium, the major protein phosphatase was purified. This enzyme was dissociated with 80% ethanol treatment, its activity was slightly increased (30%) with heparine and largely enhanced (1.5 to 3-fold) with polycations. This enzyme could be classified as a type 2A protein phosphatase. It is composed of a catalytic subunit and other subunits. Its optimum pH value is 7.2, the apparent Km for casein is 37 microM and the apparent velocity 3.6 pmol hydrolyzed32 Pi min-1 pmol-1 enzyme.
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PMID:Purification and characterization of a type 2A protein phosphatase from Yarrowia lipolytica grown on a phosphate-deficient medium. 924 23


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