Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A phase III randomized clinical trial was undertaken to compare the efficacy, side effects and acceptability of a combined monthly injectable preparation containing NET-oenanthate (NET-OEN) (50 mg) plus oestradiol valerate (E2 Val.) (5 mg) with NET-OEN only (200 mg) given every two months. A total of 849 subjects were observed for 7817 woman-months of contraceptive use. Net discontinuation rates due to involuntary pregnancy at 12 months were 0.2 and 1.1 per 100 users for one monthly and two monthly injectable preparations, respectively. Although the monthly preparation was found to be efficacious and the subjects using the monthly preparation had a better bleeding pattern, the net discontinuation rate at 12 months due to menstrual disturbances did not show any significant difference between the two preparations. With proper counselling and motivational strategies, it is likely that acceptability of monthly injectables can be further enhanced.
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PMID:A multicentre phase III comparative study of two hormonal contraceptive preparations NET-OEN (50 mg) + E2 valerate (5 mg) given every month and NET-OEN (200 mg) given every 2 months as intramuscular injection--a report of 12-month study. Indian Council of Medical Research Task Force on Hormonal Contraception. 196 85

The mouse fibroblastic cell line LM(TK-) is unable to grow at external K+ concentrations below a threshold value of 0.4 mM. At subthreshold K+ concentrations, LM(TK-) cells rapidly lose intracellular K+ and eventually lyse. We have analyzed the pathway primarily responsible for K+ efflux under these experimental conditions and reports its specific inhibition by two diuretics, furosemide and bumetanide. Bumetanide, an analog of furosemide, was a more potent inhibitor (by several orders of magnitude) than was furosemide itself. The effects of ouabain and bumetanide were additive, suggesting independence of diuretic-sensitive K+ efflux from Na+/K+ pump-mediated fluxes. Characterization of K+ efflux in LTK-5, a mutant derived from LM(TK-) and selected for its ability to grow at 0.2 mM K+ indicated that the mutant had lost the diuretic-sensitive K+ efflux pathway. Net cation fluxes, steady-state intracellular cation concentrations, and growth at reduced K+ concentrations were comparable for LM(TK-) cells maximally inhibited by diuretics and for the LTK-5 mutant grown either in the presence or absence of diuretics. Thus, reduction in K+ efflux, either by diuretic addition diuretics. Thus, reduction in K+ efflux, either by diuretic addition or by genetic alteration, can permit the cell to maintain normal cation gradients and to grow at otherwise subthreshold external K+ concentrations.
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PMID:Reduction of K+ efflux in cultured mouse fibroblasts, by mutation or by diuretics, permits growth in K+-deficient medium. 694 Jan 22

Ras signaling appears to be mediated in part by transcription factors that belong to the ets gene family. To identify downstream targets for the Ras signal transduction pathway, we have used Ras-transformed mouse fibroblasts to isolate a new member of the ets gene family, net. Net has sequence similarity in three regions with the ets factors Elk1 and SAP1, which have been implicated in the serum response of the fos promoter. Net shares various properties with these proteins, including the ability to bind to ets DNA motifs through the Ets domain of the protein and form ternary complexes with the serum response factor SRF on the fos serum response element, SRE. However, Net differs from Elk1 and SAP1 in a number of ways. The pattern of net RNA expression in adult mouse tissues is different. Net has negative effects on transcription in a number of assays, unlike Elk1. Strikingly, Ras, Src, and Mos expression switch Net activity to positive. The study of Net should help in understanding the interplay between Net and other members of the Elk subfamily and their contribution to signal transduction through Ras to the nucleus.
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PMID:Net, a new ets transcription factor that is activated by Ras. 795 35

Net overexpression or derangements of PTK-encoding oncogenes and ras serve as critical driving forces in the evolution of many epithelial and lymphohematopoietic cancers. The ability to impede signal transduction through ras-based pathways could provide a powerful molecular target for therapy and prevention of a broad spectrum of malignant neoplasms.
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PMID:Oncology and hematology. 818 56

Activation of the rat prolactin (rPRL) promoter by Ras is a prototypical example of tissue-specific transcriptional regulation in a highly differentiated cell type. Using a series of site-specific mutations and deletions of the proximal rPRL promoter we have mapped the major Ras/Raf response element (RRE) to a composite Ets-1/GHF-1 binding site located between positions -217 and -190. Mutation of either the Ets-1 or GHF-1 binding sites inhibits Ras and Raf activation of the rPRL promoter, and insertion of this RRE into the rat growth hormone promoter confers Ras responsiveness. We show that Ets-1 is expressed in GH4 cells and, consistent with their functional synergistic interaction, both Ets-1 and GHF-1 are able to bind specifically to this bipartite RRE. We confirm that Ets-1 or a related Ets factor is the nuclear target of the Ras pathway leading to activation of the rPRL promoter and demonstrate that Elk-1 and Net do not mediate the Ras response. Thus, the pituitary-specific POU homeodomain transcription factor, GHF-1, serves as a cell-specific signal integrator by functionally interacting with an Ets-1-like factor, at uniquely juxtaposed binding sites, thereby targeting an otherwise ubiquitous Ras signaling pathway to a select subset of cell-specific GHF-1-dependent genes.
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PMID:GHF-1/Pit-1 functions as a cell-specific integrator of Ras signaling by targeting the Ras pathway to a composite Ets-1/GHF-1 response element. 879 30

The paired box transcription factor Pax-5 (B-cell-specific activator protein) is a key regulator of lineage-specific gene expression and differentiation in B-lymphocytes. We show that Pax-5 functions as a cell type-specific docking protein that facilitates binding of the early B-cell-specific mb-1 promoter by proteins of the Ets proto-oncogene family. Transcriptional activity of the mb-1 promoter in pre-B-cells is critically dependent on binding sites for Pax-5:Ets complexes. Ternary complex assembly requires only the Pax-5 paired box and ETS DNA-binding domains. Mutation of a single base pair in the ternary complex binding site allows for independent binding by Ets proteins but, conversely, inhibits the binding of Pax-5 by itself. Strikingly, the mutation reverses the pattern of complex assembly: Ets proteins recruit Pax-5 to bind the mutated sequence. Recruitment of Net and Elk-1, but not SAP1a, by Pax-5 defines a functional difference between closely related Ets proteins. Replacement of a valine (V68) in the ETS domain of SAP1a by aspartic acid (as found in c-Ets-1, Elk-1, and Net) enhanced ternary complex formation by more than 60-fold. Together, these observations define novel transcription factor interactions that regulate gene expression in B cells.
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PMID:Pax-5 (BSAP) recruits Ets proto-oncogene family proteins to form functional ternary complexes on a B-cell-specific promoter. 880 14

Three multiparous Holstein cows (607 kg of BW) were surgically prepared with an elevated carotid artery and indwelling catheters in the hepatic, portal, and two mesenteric veins to study the effects of methionine supplementation on amino acid metabolism during the last 2 wk of pregnancy. The study began 15 d before the expected calving date. Dietary treatments were Control (1.53 Mcal NE(l)/kg, 15.6% CP, and 40% ruminally undegradable protein) and Control supplemented with 60 g/d of ruminally protected methionine (MET, supplying 39 g/d of DL-methionine and approximately 18 g/d of methionine available for intestinal absorption). Each cow received both dietary treatments in a crossover design. Cows were fed once daily. After 5 d on treatment, a blood flow marker (para-aminohippurate) was infused into a mesenteric vein, and arterial, portal, and hepatic blood samples were obtained at 0, 2, 6, 12, and 18 h after feeding. Net flux of methionine was calculated as the plasma arteriovenous difference multiplied by plasma flow. Dry matter intake (10.8 kg/d) and portal (824 L/h) and hepatic (995 L/h) plasma flows were not affected (P > .10) by treatment. Arterial plasma concentration of methionine was greater (P = .10) with MET (27.67 microM) than with Control (16.42 microM). Net portal absorption of methionine increased (P = .10) with MET (26.2 g/d) compared with Control (9.5 g/d). The net portal methionine flux was negatively correlated (r = -.59; P < .001) with arterial urea concentrations. Net flux of methionine across splanchnic tissues shifted (P = .06) from a net uptake with Control (4 g/d) to a net output with MET (11 g/d). Therefore, MET increased by 15 g/d the methionine supply to the rest of the body. The net uptake of methionine by splanchnic tissues observed with Control indicated a net mobilization of methionine by peripheral tissues. Results indicate that methionine was the limiting amino acid with Control and that MET was beneficial because it increased methionine supply to peripheral tissues and reduced arterial urea concentrations.
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PMID:Response of nitrogen metabolism in preparturient dairy cows to methionine supplementation. 1076 83

The ternary complex factors (TCFs), Elk-1, Sap-1a and Net, are key integrators of the transcriptional response to different signalling pathways. Classically, three MAP kinase pathways, involving ERK, JNK, and p38, transduce various extracellular stimuli to the nucleus. Net is a repressor that is converted into an activator by Ras/ERK signalling. Net is also exported from the nucleus in response to stress stimuli transduced through the JNK pathway, leading to relief from repression. Here we show that ERK and p38 bind to the D box and that binding is required for phosphorylation of the adjacent C-terminally located C-domain. The D box as well as the phosphorylation sites in the C-domain (the DC element) are required for transcription activation by Ras. On the other hand, JNK binds to the J box in the middle of the protein, and binding is required for phosphorylation of the adjacent EXport motif. Both the binding and phosphorylation sites (the JEX element) are important for Net export. In conclusion, specific targeting of Net by MAP kinase pathways involves two different docking sites and phosphorylation of two different domains. These two elements, DC and JEX, mediate two distinct functional responses.
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PMID:The ternary complex factor Net contains two distinct elements that mediate different responses to MAP kinase signalling cascades. 1104 94

The ternary complex factors (TCFs) Net, Elk-1 and Sap-1 regulate immediate early genes through serum response elements (SREs) in vitro, but, surprisingly, their in vivo roles are unknown. Net is a repressor that is expressed in sites of vasculogenesis during mouse development. We have made gene-targeted mice that express a hypomorphic mutant of Net, Net delta, which lacks the Ets DNA-binding domain. Strikingly, homozygous mutant mice develop a vascular defect and up-regulate an immediate early gene implicated in vascular disease, egr-1. They die after birth due to respiratory failure, resulting from the accumulation of chyle in the thoracic cage (chylothorax). The mice have dilated lymphatic vessels (lymphangiectasis) as early as E16.5. Interestingly, they express more egr-1 in heart and pulmonary arteries at E18.5. Net negatively regulates the egr-1 promoter and binds specifically to SRE-5. Egr-1 has been associated with pathologies involving vascular stenosis (e.g. atherosclerosis), and here egr-1 dysfunction could possibly be associated with obstructions that ultimately affect the lymphatics. These results show that Net is involved in vascular biology and egr-1 regulation in vivo.
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PMID:Net-targeted mutant mice develop a vascular phenotype and up-regulate egr-1. 1156 78

Tree carbon (C) uptake (net primary productivity excluding fine root turnover, NPP') in a New Zealand Pinus radiata D. Don plantation (42 degrees 52' S, 172 degrees 45' E) growing in a region subject to summer soil water deficit was investigated jointly with canopy assimilation (A(c)) and ecosystem-atmosphere C exchange rate (net ecosystem productivity, NEP). Net primary productivity was derived from biweekly stem diameter growth measurements using allometric relations, established after selective tree harvesting, and a litterfall model. Estimates of A(c) and NEP were used to drive a biochemically based and environmentally constrained model validated by seasonal eddy covariance measurements. Over three years with variable rainfall, NPP' varied between 8.8 and 10.6 Mg C ha(-1) year(-1), whereas A(c) and NEP were 16.9 to 18.4 Mg C ha(-1) year(-1) and 5.0-7.2 Mg C ha(-1) year(-1), respectively. At the end of the growing season, C was mostly allocated to wood, with nearly half (47%) to stems and 27% to coarse roots. On an annual basis, the ratio of NEP to stand stem volume growth rate was 0.24 +/- 0.02 Mg C m(-3). The conservative nature of this ratio suggests that annual NEP can be estimated from forest yield tables. On a biweekly basis, NPP' repeatedly lagged A(c), suggesting the occurrence of intermediate C storage. Seasonal NPP'/A(c) thus varied between nearly zero and one. On an annual basis, however, NPP'/A(c) was 0.54 +/- 0.03, indicating a conservative allocation of C to autotrophic respiration. In the water-limited environment, variation in C sequestration rate was largely accounted for by a parameter integrative for changes in soil water content. The combination of mensurational data with canopy and ecosystem C fluxes yielded an estimate of heterotrophic respiration (NPP' - NEP) approximately 30% of NPP' and approximately 50% of NEP. The estimation of fine-root turnover rate is discussed.
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PMID:Net ecosystem productivity, net primary productivity and ecosystem carbon sequestration in a Pinus radiata plantation subject to soil water deficit. 1265 99


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