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:3.4.11.18 (MAP)
7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Onconase, a cytotoxic ribonuclease from Rana pipiens, possesses pyroglutamate (Pyr) at the N-terminus and has a substrate preference for uridine-guanine (UG). To identify residues responsible for onconase's cytotoxicity, we cloned the rpr gene from genomic DNA and expressed it in Escherichia coli BL21(DE3). The recombinant onconase with Met at the N-terminus had reduced thermostability, catalytic activity and antigenicity. Therefore, we developed two methods to produce onconase without Met. One relied on the endogeneous E.coli methionine aminopeptidase and the other relied on the cleavage of a pelB signal peptide. The Pyr1 substitutional variants maintained similar secondary structures to wild-type onconase, but with less thermostability and specific catalytic activity for the innate substrate UG. However, the non-specific catalytic activity for total RNAs varied depending on the relaxation of base specificity. Pyr1 promoted the structural integrity by forming a hydrogen bond network through Lys9 in alpha1 and Val96 in beta6, and participated in catalytic activity by hydrogen bonds to Lys9 and P(1) catalytic phosphate. Residues Thr35 and Asp67 determined B(1) base specificity, and Glu91 determined B(2) base specificity. The cytotoxicity of onconase is largely determined by structural integrity and specific catalytic activity for UG through Pyr1, rather than non-specific activity for total RNAs.
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PMID:The structural integrity exerted by N-terminal pyroglutamate is crucial for the cytotoxicity of frog ribonuclease from Rana pipiens. 1473 64

We identified and cloned the mouse orthologue of human GPR6 as a new member of the lysophospholipid-receptor family. Sphingosine-1-phosphate (S1P) activated GPR6, transiently expressed in frog oocytes or in Chinese hamster ovary (CHO) cells, with high specificity and nanomolar affinity. The GPR6 gene was found to be located on chromosome 10B1 and a single exon coded for the entire open-reading frame. Signal transduction of S1P was inhibited by pertussis toxin, suggesting a coupling of GPR6 to an inhibitory G protein. In CHO cells transfected with GPR6, the sphingosine-kinase pathway mediated Ca(2+) mobilization from internal stores. Apoptotic cell death was induced by serum deprivation or H(2)O(2) treatment and was prevented by S1P in GPR6-, but not in vector-transfected CHO cells. The antiapoptotic effect of S1P required activation of sphingosine kinase and was accompanied by an increase in MAP-kinase phosphorylation.
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PMID:Sphingosine-1-phosphate is a high-affinity ligand for the G protein-coupled receptor GPR6 from mouse and induces intracellular Ca2+ release by activating the sphingosine-kinase pathway. 1459 18

Sphingosine-1-phosphate (S1P) is a lipid mediator that exerts multiple cellular functions through activation of G-protein-coupled receptors. Although the role of S1P on angiogenesis is well established, its role in neurogenesis is unknown. We examined the effects of S1P on G-protein activation in brain sections of rat embryo and on neural progenitor cells in culture. Intense S1P-stimulated [35S]GTPgammaS labeling was observed as early as E15 in the neuroepithelium and differentiating fields throughout the brain, suggesting that functional S1P receptors are expressed in brain areas with active neurogenesis. mRNA transcripts for several S1P receptor subtypes (S1P1, S1P2, S1P3 and S1P5) were expressed in neural progenitor cells prepared from embryonic rat hippocampus. S1P induced phosphorylation of extracellular signal-regulated kinase (ERK) and proliferation of neural progenitor cells as determined by BrdU incorporation in a pertussis toxin-sensitive manner. These effects were prevented by the ERK signaling inhibitor U0126. S1P augmented telomerase activity in neural progenitor cells with similar potency as that of FGF-2. Furthermore, S1P induced cell-cell aggregation. This morphological change was transient and prevented by Y-27632, an inhibitor of Rho-associated kinase. These results suggest that S1P plays a pleiotropic role in neurogenesis via pathways involving S1P receptors, MAP kinases and Rho kinase.
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PMID:Sphingosine-1-phosphate induces proliferation and morphological changes of neural progenitor cells. 1475 25

Short-term regulation of catecholamine biosynthesis involves reversible phosphorylation of several serine residues in the N-terminal regulatory domain of tyrosine hydroxylase. The MAP kinases ERK1/2 have been identified as responsible for phosphorylation of Ser31. As an initial step in elucidating the effects of phosphorylation of Ser31 on the structure and activity of tyrosine hydroxylase, the kinetics of phosphorylation of the rat enzyme by recombinant rat ERK2 have been characterized. Complete phosphorylation results in incorporation of 2mol of phosphate into each subunit of tyrosine hydroxylase. The S8A and S31A enzymes only incorporate a single phosphate, while the S19A and S40A enzymes incorporate two. Phosphorylation of S8A tyrosine hydroxylase is nine times as rapid as phosphorylation of the S31A enzyme, consistent with a ninefold preference of ERK2 for Ser31 over Ser8.
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PMID:Specificity of the MAP kinase ERK2 for phosphorylation of tyrosine hydroxylase. 1500 89

Endothelial dysfunction is characterized by multiple interactions between endothelial cells and components of the blood. This study focussed on the induction of the pro-atherogenic connective tissue growth factor (CTGF) in endothelial cells by bioactive lipids and platelets. Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) led to a time- and concentration-dependent increase in CTGF mRNA and protein expression in the human endothelial cell line EAHY 926 and in primary cultures of human umbilical vein endothelial cells (HUVEC). As both cell types expressed various receptors for LPA and S1P, signaling pathways were further characterized by pharmacological means: induction of CTGF was pertussis toxin-insensitive and inhibition of activation of p42/44 MAP kinases only partially reduced CTGF expression. On the contrary, interference with the RhoA signaling pathway by simvastatin, an inhibitor of geranylgeranyltransferases, or the Rho-kinase inhibitor Y27632 prevented induction of CTGF. Co-incubation of endothelial cells with freshly isolated human platelets significantly increased the expression of CTGF mRNA in endothelial cells, which was also sensitive to simvastatin. Up-regulation of CTGF in endothelial cells, induced by LPA, S1P, or platelets, may contribute to the initiation and progression of atherosclerosis. Interference of simvastatin with the synthesis of this pro-atherogenic factor further supports the anti-atherogenic role of statins.
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PMID:Induction of connective tissue growth factor (CTGF) in human endothelial cells by lysophosphatidic acid, sphingosine-1-phosphate, and platelets. 1526 82

In order to recycle magnesium ammonium phosphate (MgNH4PO4.6H2O: MAP) obtained from MAP process, which is one of the attractive processes for removal of aqueous ammonium and phosphate from wastewater, ammonium elimination from MAP to magnesium phosphates and ammonium incorporation into the magnesium phosphates have been investigated in the present study. It is confirmed that magnesium hydrogen phosphate (MgHPO4) is favorably obtained from the ammonium elimination from MAP at temperatures greater than 353 K, although magnesium phosphate (Mg3(PO4)2) and magnesium pyrophosphate (Mg2P2O7) have been suggested as possible candidates. Based on the dissolution-precipitation mechanism for the removal of aqueous ammonium with magnesium phosphates, three magnesium phosphates were employed for the removal of aqueous ammonium. The order of the removal rate of the aqueous ammonium was MgHPO4>Mg3(PO4)2>Mg2P2O7, as expected from the solubility of those magnesium phosphates. The removability of the solid obtained from ammonium elimination of MAP is also confirmed. The present results show that MAP can be employed as an advanced material for the removal/recovery of ammonium, although it is generally accepted that an excess of MAP obtained from the wastewater treatment can be only used as a slow-acting fertilizer.
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PMID:Removal of aqueous ammonium with magnesium phosphates obtained from the ammonium-elimination of magnesium ammonium phosphate. 1602 61

Hematopoietic tyrosine phosphatase (HePTP) is a 38kDa class I non-receptor protein tyrosine phosphatase (PTP) that is strongly expressed in T cells. It is composed of a C-terminal classical PTP domain (residues 44-339) and a short N-terminal extension (residues 1-43) that functions to direct HePTP to its physiological substrates. Moreover, HePTP is a member of a recently identified family of PTPs that has a major role in regulating the activity and translocation of the MAP kinases Erk and p38. HePTP binds Erk and p38 via a short, highly conserved motif in its N terminus, termed the kinase interaction motif (KIM). Association of HePTP with Erk via the KIM results in an unusual, reciprocal interaction between the two proteins. First, Erk phosphorylates HePTP at residues Thr45 and Ser72. Second, HePTP dephosphorylates Erk at PTyr185. In order to gain further insight into the interaction of HePTP with Erk, we determined the structure of the PTP catalytic domain of HePTP, residues 44-339. The HePTP catalytic phosphatase domain displays the classical PTP1B fold and superimposes well with PTP-SL, the first KIM-containing phosphatase solved to high resolution. In contrast to the PTP-SL structure, however, HePTP crystallized with a well-ordered phosphate ion bound at the active site. This resulted in the closure of the catalytically important WPD loop, and thus, HePTP represents the first KIM-containing phosphatase solved in the closed conformation. Finally, using this structure of the HePTP catalytic domain, we show that both the phosphorylation of HePTP at Thr45 and Ser72 by Erk2 and the dephosphorylation of Erk2 at Tyr185 by HePTP require significant conformational changes in both proteins.
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PMID:Structure of the hematopoietic tyrosine phosphatase (HePTP) catalytic domain: structure of a KIM phosphatase with phosphate bound at the active site. 1622 75

In this paper, phosphorus balances are calculated for the wastewater purification and sludge treatment stages for wastewater treatment plants (WWTPs) applying Enhanced Biological Phosphorus Removal (EBPR). The possible P-recovery potential is then estimated and evaluated regarding different locations along the process of wastewater purification and sludge treatment, taking the different phosphorus bonding forms into account. Caused by the more favourable bonding forms in the excess sludge as well as possibly also in the sludge ash a recovery of the phosphorus seems especially favoured for WWTPs with EBPR. The processes available for a P recycling are named, and special regard is given to the Phostrip-process, which is a possible recycling process already tested in practice. Further R&D demand consists in basic research regarding disintegration, fermentation or acidic total digestion of excess sludge followed by phosphorus precipitation including separation of the precipitates, MAP-precipitation and separation from digested sludge and on the ability to extract phosphorus and heavy metals from sewage sludge ash. These investigations are a precondition to enable purposeful process developments. At the present state the cost of recycled phosphorus earned from wastewater, sludge and ash, respectively, are a multiple higher than the costs for raw phosphate taking into account the suitable processes. Thus, up to now no phosphorus recycling with a defrayal of costs is possible. The future importance of phosphorus recycling will depend on the market price for raw phosphate, the recycling costs and, furthermore, on the general political framework.
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PMID:Phosphorus recycling in sewage treatment plants with biological phosphorus removal. 1645 32

A novel granular medium consisting (1.5-5 mm in diameter) of inert perlite particles as nuclei and an effective surface layer containing sulfur, CaCO3 and Mg(OH)2 was developed for advanced treatment of agro-industrial wastewater. The performance of the medium was examined with a laboratory-scale down-flow fixed-bed column reactor using piggery wastewater, which had been treated by an upflow anaerobic sludge blanket reactor and a trickling filter. The removal efficiency of NOx- -N was more than 70% with a NOx- -N loading rate of less than approximately 0.3 kg Nm(-3) d(-1); the removal efficiency dropped due to the accumulation of nitrite when the loading rate exceeded that value. A significant drop of phosphate and Mg2+ concentrations occurred when the effluent pH exceeded 7.9. Ammonium was removed with an average removal efficiency of 12.4%. These results indicated that the crystalline reaction of PO4(3-), Mg2+ and NH4+ (MAP reaction) under alkaline conditions contributed to the removal of phosphate. This medium could be useful for the simultaneous reduction of nitrogenous and phosphorus compounds in biologically treated agro-industrial wastewater.
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PMID:Autotrophic denitrification and chemical phosphate removal of agro-industrial wastewater by filtration with granular medium. 1670 61

1alpha-25-Dihydroxyvitamin D3 (calcitriol), the biologically active metabolite of vitamin D, is known to regulate calcium and phosphate levels in bone metabolism. It is also known to influence proliferation and differentiation in carcinoma cells mediated by the vitamin D receptor (VDR). The antiproliferative effects of calcitriol are believed to be mediated by the nuclear pathway via binding the activated receptor to vitamin D-responsive elements. This induces the vitamin D-responsive genes. Another possible pathway might be the MAPK-cascade or rapid response pathway. The interaction of calcitriol and the MAP-kinase-cascade was evaluated on VDR-positive MCF-7 cells and VDR-negative MDA-MB-231 breast cancer cells. The cells were incubated with calcitriol solution at 10(-7) M and 10(-9) M, or ethanol as controls, for up to 48 h. The effects of calcitriol were measured by semi-quantitative Western blotting. Calcitriol stimulated the MAP-kinases ERK1 and ERK2. A biphasic activation was found for calcitriol in VDR-positive cells after incubation for 5 to 20 min and from 2 to 24 h. However, early activation of ERK1 and ERK2 was also demonstrated in VDR-negative cells. In the controls, ethanol also induced the MAPK-cascade at 5 to 10 min. Calcitriol induction was demonstrated after incubation from 2 to 24 h. In conclusion, it seems that the early induction of the MAPK-cascade was independent of the VDR. A calcitriol-induced MAPK activation was shown after 4 h, which may have been caused by activation of the nuclear receptor pathway.
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PMID:Modulation of MAPK ERK1 and ERK2 in VDR-positive and -negative breast cancer cell lines. 1688 87


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