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

The activities of nuclear envelope-associated protein phosphokinase and protein phosphatase were determined in nuclear ghosts from liver and oviduct of quails. The protein kinase was found to be inhibited by poly(A) by 75%. During the kinase reaction proteins with molecular weights of 106 000 and 64 000 were phosphorylated. The phosphoprotein phosphatase from liver was stimulated to 190% by poly(A), whereas only a slight enhancing effect by this polymer was determined with the oviduct enzyme (to 125%). Comparative determinations of the nuclear ghost-associated enzyme activities revealed the following values (in nmol Pi/min per 10(8) ghosts); oviduct: phosphokinase, 0.015; phosphatase, 0.004 and nucleoside triphosphatase, 39.4; and liver: phosphokinase, 0.044; phosphatase, 0.012 and nucleoside triphosphatase, 11.7. These data indicate that phosphorylation/dephosphorylation proceeds independently of the nucleoside triphosphatase cycle. This assumption is supported by analytical results revealing that no marked dephosphorylation occurs after poly(A) binding to the nuclear envelope. Moreover, stoichiometrical data showed a nearly 1:1 molar ratio between ATP-binding and phosphorylation of nuclear envelope protein. From these findings a new model for the nucleoside triphosphatase-mediated poly(A)(+)mRNA efflux from nuclei is deducted, proposing phosphokinase and phosphatase only to modulate the affinity of the 'carrier structure' for poly(A) (+)mRNA, but not to constitute the nucleoside triphosphatase.
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PMID:The role of protein phosphokinase and protein phosphatase during the nuclear envelope nucleoside triphosphatase reaction. 632 88

It has been demonstrated earlier that the administration of tryptophan to fasted animals increased the levels of mRNA in the cytoplasm of the liver by stimulating the translocation of nuclear poly(A)-mRNA into the cytoplasm. Also, tryptophan increased the activity of hepatic nuclear envelope (NE) nucleoside triphosphatase, an enzyme considered to be involved in nucleocytoplasmic translocation of mRNA. In this study, the activities of two other NE-associated enzymes, protein phosphokinase and phosphoprotein phosphohydrolase, also implicated in nuclear RNA transport, were investigated in the livers of rats that received a single tube feeding of tryptophan. The administration of tryptophan to fasted rats 10 minutes before killing increased the hepatic NE activities of both enzymes, protein phosphokinase and phosphoprotein phosphohydrolase. Furthermore, tryptophan administration increased the in vivo incorporation of 3H-leucine into NE proteins (+83%) and into other subcellular fractions (+34 to +43%) of the liver compared with that into corresponding fractions of the control rats. Rats that received 3H-leucine to prelabel hepatic proteins and then were treated with puromycin to inhibit further protein synthesis followed by tube feeding of tryptophan revealed greater radioactivity associated with NE proteins than that in controls. These findings suggest that tryptophan may act to stimulate the transport or availability of proteins to the vicinity of the NE, possibly specific regulatory proteins, such as nucleoside triphosphatase, protein phosphokinase and phosphoprotein phosphohydrolase, which show an increase in activity and may then be responsible for the increase in the rate of nucleocytoplasmic translocation of mRNA.
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PMID:Effect of tryptophan on enzymes and proteins of hepatic nuclear envelopes of rats. 682 5

Dynamin I is a nerve terminal phosphoprotein with intrinsic guanosine triphosphatase (GTPase) activity that is required for endocytosis. Upon depolarization and synaptic vesicle recycling, dynamin I undergoes a rapid dephosphorylation. Dynamin I was found to be a specific high-affinity substrate for calcineurin in vitro. At low concentrations, calcineurin dephosphorylated dynamin I that had been phosphorylated by protein kinase C. The dephosphorylation inhibited dynamin I GTPase activity in vitro and after depolarization of nerve terminals. The effect in nerve terminals was prevented by the calcineurin inhibitor cyclosporin A. This suggests that in nerve terminals, calcineurin serves as a Ca(2+)-sensitive switch for depolarization-evoked synaptic vesicle recycling.
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PMID:Calcineurin inhibition of dynamin I GTPase activity coupled to nerve terminal depolarization. 805 58

Previous studies demonstrated that the mammalian mRNA capping enzyme is a bifunctional enzyme containing RNA 5'-triphosphatase and mRNA guanylyl-transferase activities in a single polypeptide. In yeast, both the above activities are separated into two different subunits, alpha and beta, the genes for which we have cloned recently. It is thus interesting to compare the structural and functional relationships between the mammalian and yeast capping enzymes. Here we isolated two human cDNAs encoding mRNA capping enzymes termed hCAP1a and hCAP1b which encode 597 and 541 amino acids, respectively. They are different only at the region coding for the C-terminal portion of the enzyme. Comparison of the deduced amino acid sequences with other cellular and viral capping enzymes showed that all the regions conserved among mRNA guanylyltransferases are observed in our clones except one conserved C-terminal region which was absent in the hCAP1b protein. The purified recombinant hCAP1a gene product, hCAP1a, exhibited both RNA 5'-triphosphatase and mRNA guanylyltransferase activities. Deletion mutant analysis of hCAP1a showed that the N-terminal 213 amino acid fragment containing a tyrosine specific protein phosphatase motif catalyzed the RNA 5'-triphosphatase activity and the C-terminal 369 amino acid fragment exhibited the mRNA guanylyltransferase activity. On the other hand, hCAP1b showed RNA 5'-triphosphatase activity, but neither enzyme-GMP covalent complex formation nor cap structure formation was detected.
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PMID:Cloning and characterization of two human cDNAs encoding the mRNA capping enzyme. 947 87

The tescalcin gene is preferentially expressed during mouse testis differentiation. Here, we demonstrate that this gene encodes a 24 kDa Ca(2+)- and Mg(2+)-binding protein with one consensus EF-hand and three additional domains with EF-hand homology. Equilibrium dialysis with (45)Ca(2+) revealed that recombinant tescalcin binds approximately one Ca(2+) ion at physiological concentrations (pCa 4.5). The intrinsic tryptophan fluorescence of tescalcin was significantly reduced by Ca(2+), indicative of a conformational change. The apparent K(d) for Ca(2+) was 0.8 microM. A point mutation in the consensus EF-hand (D123A) abolished (45)Ca(2+) binding and prevented the fluorescence quenching, demonstrating that the consensus EF-hand alone mediates the Ca(2+)-induced conformational change. Tescalcin also binds Mg(2+) (K(d) 73 microM), resulting in a much smaller fluorescence decrease. In the presence of 1 mM Mg(2+), tescalcin's Ca(2+) affinity is shifted to 3.5 microM. These results illustrate that tescalcin should bind Mg(2+) constitutively in a quiescent cell, replacing it with Ca(2+) during stimulation. We also show that tescalcin is most abundant in adult mouse heart, brain, and stomach, as well as in HeLa and HL-60 cells. Immunofluorescence microscopy revealed that tescalcin is present in the cytoplasm and nucleus, with concentration in membrane ruffles and lamellipodia in the presence of serum, where it colocalizes with the small guanosine triphosphatase Rac-1. Tescalcin shares sequence and functional homology with calcineurin-B homologous protein (CHP), and we found that tescalcin, like CHP, can inhibit the phosphatase activity of calcineurin A. Hence, tescalcin is a novel calcineurin B-like protein that binds a single Ca(2+) ion.
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PMID:Characterization of tescalcin, a novel EF-hand protein with a single Ca2+-binding site: metal-binding properties, localization in tissues and cells, and effect on calcineurin. 1466 68

There is great interest in deciphering mechanisms of maladaptive remodeling in cardiac hypertrophy in the hope of affording clinical benefit. Potential targets of therapeutic intervention include the cytoplasmic phosphatase calcineurin and small guanosine triphosphate-binding proteins, such as Rac1 and RhoA, all of which have been implicated in maladaptive hypertrophy. However, little is known about the interaction-if any-between these important signaling molecules in hypertrophic heart disease. In this study, we examined the molecular interplay among these molecules, finding that Rho family guanosine triphosphatase signaling occurs either downstream of calcineurin or as a required, parallel pathway. It has been shown that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition blocks hypertrophy, and we report here that "statin" therapy effectively suppresses small G protein activation and blunts hypertrophic growth in vitro and in vivo. Importantly, despite significant suppression of hypertrophy, clinical and hemodynamic markers remained compensated, suggesting that the hypertrophic growth induced by this pathway is not required to maintain circulatory performance.
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PMID:Guanosine triphosphatase activation occurs downstream of calcineurin in cardiac hypertrophy*. 1635 80