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:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genome analyses have shown that plants contain gene families encoding various components of mitogen-activated protein kinase (MAPK) signaling pathways. Previous reports have described the involvement of MAPK pathways in stress and pathogen responses of leaves and suspension-cultured cells. Here we show that auxin treatment of Arabidopsis roots transiently induced increases in protein kinase activity with characteristics of mammalian ERK-like MAPKs. The MAPK response we monitored was the result of hormonal action of biologically active auxin, rather than a stress response provoked by auxin-like compounds. Auxin-induced MAPK pathway signaling was distinguished genetically in the Arabidopsis auxin response mutant axr4, in which MAPK activation by auxin, but not by salt stress, was significantly impaired. Perturbation of MAPK signaling in roots using inhibitors of a mammalian MAPKK blocked auxin-activated transgene expression in BA3-GUS seedlings, while potentiating higher than normal levels of MAPK activation in response to auxin. Data presented here indicate that MAPK pathway signaling is positively involved in auxin response, and further suggest that interactions among MAPK signaling pathways in plants influence plant responses to auxin.
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PMID:Auxin induces mitogenic activated protein kinase (MAPK) activation in roots of Arabidopsis seedlings. 1113 12

The conformational and quantum analyses of dental adhesive carboxylic acid and carboxylic acid anhydride monomers were preformed. Conformational analyses were carried out by a molecular mechanics calculation. 4-META and 4-AETA showed more compact conformation than 4-MET. Quantum analyses were performed by semi-empirical molecular orbital calculation. 4-MET had a higher dipole moment, polarizability, and HOMO and LUMO energy than 4-META and 4-AETA. The bond lengths and bond orders of the carbonyl groups of the trimellitic acid moiety of 4-MET were different from those of carbonyl groups of the trimellitate anhydride moieties of 4-META and 4-AETA. Oxygen of the methacryloyl or acryloyl groups showed the highest electron densities among the oxygen atoms for all monomers. The superdelocalizabilities of oxygen atoms of the trimellitic acid moiety of 4-MET were greater than that of oxygen of the methacryloyl group. A small change in the bond length of the Ca-O bond showed a large difference in the steric energies of 4-MET/Ca salt.
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PMID:Conformational and quantum analysis of dental adhesive carboxylic acid and carboxylic acid anhydride monomers. 1144 82

In the present work, the occurrence of yeasts in different types of typical Sardinian ewe's cheeses (32 samples of pecorino, 32 of caciotta, 40 of feta, 56 of ricotta) was determined. For the strains isolated the following properties were studied: proteolytic and lipolytic activities, the ability to grow at different temperatures, different concentrations of salt, and to assimilate and/or ferment compounds like lactate, citrate, lactose, glucose, galactose, lactic acid. Of 160 samples analysed, 76.2% yielded growth of yeasts. Yeast counts showed a certain variability among the samples. The highest levels were observed in caciotta and feta cheeses. A total of 281 strains belonging to 16 genera and 25 species were identified. In general, Debaryomyces hansenii was the dominant species, representing 28.8% of the total isolates. Other frequently appearing species were Geotrichum candidum, Kluyveromyces lactis and K. marxianus. Other genera encountered were Pichia, Candida, Dekkera, Yarrowia and Rhodotorula. With regard to the biochemical and technological properties of the yeasts, only K. lactis, K. marxianus and Dek. anomala assimilated and fermented lactose, whereas the majority of the species assimilated lactic acid. The assimilation of citrate was a characteristic of D. hansenii, R. rubra and Y. lipolytica. On the whole, the yeasts were weakly proteolytic while lipolytic activity was present in several species. A high percentage of strains showed a certain tolerance to low temperatures while only some strains of D. hansenii and K. lactis were able to grow at a 10% NaCl concentration.
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PMID:Yeasts associated with Sardinian ewe's dairy products. 1158 60

NS-417 (5-(4-Chlorophenyl)-8-methyl-6-7-8-9-tetrahydro-1-H-pyrrolo[3.2-h]isoquinoline-2,3-dione-3-oxim hydrochloric acid salt) belongs to a new chemical series of compounds. NS-417 rescued differentiated PC12 cells from death induced by withdrawal of serum and nerve growth factor. Furthermore, NS-417 stimulated neurotrophic factor-induced neurite outgrowth in undifferentiated PC12 cells. In accordance with this observation, NS-417 potentiated NGF-induced signaling, such as activation of the extracellular signal-regulated kinases ERK1 and ERK2 and the Akt kinase. NS-417 also enhanced ERK activation induced by 10 minutes stimulation with NGF, bFGF or EGF in PC12 cells. In addition to the effect in PC12 cells, NS-417 increased the number of tyrosine hydroxylase (TH) positive cells in cultures established from dissociated E14 rat ventral mesencephali.
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PMID:NS-417, a novel compound with neurotrophic-like effects. 1192 63

Overexpression of the p185/HER2 protein is seen in 20%-25% of primary breast cancers and is associated with poor prognosis. Recent phase II and III clinical trials demonstrate that trastuzumab is active against breast tumors, both as a single agent and in combination with chemotherapy. In patients with HER2-overexpressing metastatic breast cancer, use of trastuzumab in combination with chemotherapy is associated with a 20% reduction in relative risk of death and an increase in median survival from 20.3 to 25.1 months compared to chemotherapy alone. Side effects include fever and chills and an unexpected increase in doxorubicin/trastuzumab-associated cardiomyopathy. Clinical development is now focused on trastuzumab in combination with chemotherapy regimens that do not contain an anthracycline. Trastuzumab in combination with docetaxel is synergistic in vitro. Data from ongoing clinical trials are consistent with this finding. Preliminary data from 3 phase II studies suggest a 44%-63% response rate when the combination is used first or second line in HER2-overexpressing metastatic breast cancer. The combination of docetaxel with trastuzumab is well tolerated and has not been associated with significant cardiotoxicity. Given in vitro evidence that platinum salts act synergistically with trastuzumab and docetaxel, and phase II data suggesting clinical efficacy and good tolerability, the combination of platinum salt plus trastuzumab and docetaxel is now being assessed in adjuvant trials
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PMID:Combining the anti-HER2 antibody trastuzumab with taxanes in breast cancer: results and trial considerations. 1197 Jul 40

Overexpression of the HER2/neu oncogene and receptor protein has been reported in 20%-30% of patients with breast cancer and is associated with a poor prognosis. HER2/neu expression in breast cancer patients assessed by fluorescence in situ hybridization or immunohistochemistry is a predictor for response to trastuzumab, a humanized monoclonal antibody against the HER2/neu cell-surface protein. Data regarding HER2/neu expression in lung cancer are more limited, and there is little information regarding HER2/neu expression and response to trastuzumab alone or in combination with chemotherapeutic agents. Gemcitabine is an active agent against non-small-cell lung cancer (NSCLC) and has demonstrated activity in breast cancer as well. In vitro modified tetrazolium salt growth assays were performed to determine whether the combination of trastuzumab/gemcitabine produced synergistic or additive effects on breast and lung cancer cell lines. The effects of trastuzumab alone, gemcitabine alone, and the trastuzumab/gemcitabine combination was evaluated on 4 NSCLC cell lines, 1 small-cell lung cancer (SCLC) cell line, and 2 breast cancer cell lines. HER2/neu surface protein expression was assessed by fluorescence flow cytometry and immunohistochemistry. Fluorescence in situ hybridization analysis was used to study gene expression. Trastuzumab treatment alone resulted in growth inhibition in all cell lines expressing HER2/neu and the inhibitive effect correlated with the level of cell surface HER2/neu protein expression. Treatment with gemcitabine alone resulted in growth inhibition in both breast and NSCLC cell lines. A synergistic growth inhibition effect was seen with the trastuzumab/ gemcitabine combination as indicated by combination index values < 1. The degree of synergy observed did not directly correlate with the level of surface protein expression, as synergy was seen even in cancer cell lines expressing low levels of HER2/neu. No treatment effect was seen in the SCLC cell line, which did not express HER2/neu. These preclinical studies indicate a need to study the clinical synergistic effects of the gemcitabine/trastuzumab combination in breast cancer and NSCLC patients whose tumors overexpress HER2/ neu.
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PMID:Preclinical studies of gemcitabine and trastuzumab in breast and lung cancer cell lines. 1205 39

Docetaxel (Taxotere) has been intensively investigated for the treatment of metastatic breast cancer, where it has proved to be one of the most active agents. Initial phase II studies in anthracycline-resistant metastatic breast cancer demonstrated impressive response rates that have been confirmed in phase III randomized trials. Docetaxel remains the only single agent to demonstrate a survival benefit in anthracycline-resistant patients. More recently, the combination of docetaxel with capecitabine (Xeloda) has demonstrated additional improvement in survival over docetaxel alone in a randomized phase III trial. In patients previously treated with an alkylating agent, docetaxel is the only single drug to demonstrate improved efficacy over doxorubicin in a randomized trial. Docetaxel has been investigated in combination with the anthracyclines doxorubicin and epirubicin in randomized trials. The docetaxel-containing regimens have consistently demonstrated improvement over the non-docetaxel-containing regimens. The efficacy and safety of weekly docetaxel has extended the line of investigation for combinations with agents normally administered on a weekly basis, such as vinorelbine [Navelbine], gemcitabine [Gemzar], and trastuzumab [Herceptin], with promising findings. In addition, the results of the triple-drug combination of docetaxel, a platinum salt (cisplatin or carboplatin), and trastuzumab have resulted in impressive response rates and time to progression in a population of metastatic breast cancer patients with HER2/neu-positive tumors. The consistent demonstration of a high level of efficacy with manageable toxicity ensures the continued widespread investigation of docetaxel in metastatic breast cancer.
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PMID:The current status of docetaxel for metastatic breast cancer. 1210 94

This study explored the hypothesis that dietary salt promoted changes in renal expression of TGF-beta1 and NOS3 by modulating the mitogen-activated protein kinase (MAPK) pathways. Sprague-Dawley rats were maintained for four days on formulated diets that contained 0.3, 1.0, 3.0, or 8.0% NaCl. An increase in salt intake to greater than or equal to 3.0% NaCl increased kinase activities of p38 MAPK and p42/44 MAPK, but not p46/54 JNK/SAPK, in the cortex and outer and inner medulla. Associated with this increased activity was a relative increase in the phosphorylated forms of the transcription factors ATF-2 and Elk-1. Compared with rats on 0.3% NaCl diet, glomerular preparations from rats on 8.0% NaCl diet contained more NOS3 and produced greater amounts of total and active TGF-beta1 and NOx. PD-098059, a MEK1 inhibitor, and SB-203580, an inhibitor of p38 MAPKalpha-gamma, diminished NOS3 expression and production of TGF-beta1 and NOx. TEA, administered intravenously 5 min before harvesting kidneys of rats on the 8.0% NaCl diet, decreased activities of both p38 MAPK and p42/44 MAPK, compared with vehicle-treated animals. Thus, an increase in dietary salt activated through a TEA-sensitive pathway the p38 MAPK and p42/44 MAPK signaling cascades, which promoted the increase in glomerular TGF-beta1 and NOS3 expression.
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PMID:Dietary salt intake activates MAP kinases in the rat kidney. 1220 91

Angiotensin II (Ang II) is a multifunctional hormone that influences the function of cardiovascular cells through a complex series of intracellular signaling events initiated by the interaction of Ang II with AT1 and AT2 receptors. AT1 receptor activation leads to cell growth, vascular contraction, inflammatory responses and salt and water retention, whereas AT2 receptors induce apoptosis, vasodilation and natriuresis. These effects are mediated via complex, interacting signaling pathways involving stimulation of PLC and Ca2+ mobilization; activation of PLD, PLA2, PKC, MAP kinases and NAD(P)H oxidase, and stimulation of gene transcription. In addition, Ang II activates many intracellular tyrosine kinases that play a role in growth signaling and inflammation, such as Src, Pyk2, p130Cas, FAK and JAK/STAT. These events may be direct or indirect via transactivation of tyrosine kinase receptors, including PDGFR, EGFR and IGFR. Ang II induces a multitude of actions in various tissues, and the signaling events following occupancy and activation of Ang receptors are tightly controlled and extremely complex. Alterations of these highly regulated signaling pathways may be pivotal in structural and functional abnormalities that underlie pathological processes in cardiovascular diseases such as cardiac hypertrophy, hypertension and atherosclerosis.
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PMID:Recent advances in angiotensin II signaling. 1221 72

A disposable glucose biosensor based on glucose oxidase immobilized on tetrathiafulvalene-tetracyanoquinodimethane (ITF-TCNQ) conducting organic salt synthesized in situ onto an overoxidized poly(pyrrole) (PPy(ox).) film is described. The TIF-TCNQ crystals grow through the nonconducting polypyrrole film (ensuring electrical connection to the underlying Pt electrode) and emerge from the film forming a treelike structure. The PPy(ox) film prevents the interfering substances from reaching the electrode surface. The sensor behavior can be modeled by assuming a direct reoxidation of the enzyme at the surface of the TTF-TCNQ crystals. A heterogeneous rate constant around 10(-6) - 10(-7) cm s(-1) has been estimated. The biosensor is nearly oxygen- and interference-free and when integrated in a flow injection system displays a remarkable sensitivity (70 nA/mM) and stability.
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PMID:A disposable, reagentless, third-generation glucose biosensor based on overoxidized poly(pyrrole)/tetrathiafulvalene-tetracyanoquinodimethane composite. 1249 83


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