Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.12.2 (MEK)
18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new human gastric cancer cell line (MKK-1), derived from Borrmann type 3 tumor of the stomach, was established. It was obtained from poorly differentiated adenocarcinoma. The cell line grew in vitro, forming a sheet of monolayered cells and attaching firmly to the inner surface of culture vessels; it continued to grow for more than 1 year and 4 months. Its doubling time was 12.6 hours, with a chromosomal mode of 69. The cells could grow in nude mice; histological findings of the tumors developed in the mice showed a pattern similar to those in the primary tumor, i.e., poorly differentiated adenocarcinoma. With regards to tumor-related antigens, production of the CA19-9 was observed as time-dependent increase and was detected at a level of 4 U/ml in the culture supernatant on passage day 7, showing high values compared with the control. Immunostaining was positive for both the anti CEA antibody and the anti CA19-9 antibody. In sera examined in week 4 after subcutaneous transplantation of MKK-1 to the nude mice, CEA and CA19-9 levels were high, at 8.93 ng/ml and 44 U/ml, respectively. There was a positive correlation between increase in a tumor weight and the production of tumor-related antigens.
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PMID:[Establishment and characterization of a new poorly differentiated gastric cancer cell line (MKK-1), derived from Borrmann type 3 tumor]. 146 Jul 64

The amino acid sequence of the dual specificity mitogen-activated protein kinase kinase (MAPKK) has been determined by cDNA cloning and amino acid sequencing. MAPKK (393 residues, Mr 43,330) is a new member of the protein kinase subclass that comprises byr1 and STE7 that are involved in pheromone dependent signal transduction in yeast, wis1 a mitotic regulator in S. pombe and PBS2, which confers antibiotic resistance in S. cerevisiae.
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PMID:The amino acid sequence of a mammalian MAP kinase kinase. 146 59

A MAP kinase kinase kinase (MAPKKK) was identified in phaeochromocytoma (PC12) cells which reactivated homogeneous MAP kinase kinase (MAPKK) from rabbit skeletal muscle that had been inactivated by incubation with protein phosphatase 2A. Reactivation was accompanied by stoichiometric phosphorylation of MAPKK on a serine residue(s). Following stimulation of PC12 cells with nerve growth factor and chromatography of the extracts on Mono Q, MAP kinase and MAPKK were detected as active phosphorylated enzymes, whereas MAPKKK was inactive and only activated after prolonged storage at 4 degrees C. The results suggest that the activation of MAPKKK by growth factors is likely to occur by a non-covalent mechanism.
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PMID:Identification of a MAP kinase kinase kinase in phaeochromocytoma (PC12) cells. 146 86

MAP kinase kinase (MAPKK) was purified 30,000-fold to homogeneity from extracts of rabbit skeletal muscle and shown to be a monomeric protein of apparent molecular mass 44 kDa. MAPKK activated the 42 kDa isoform of MAP kinase by phosphorylation of Thr-183 and Tyr-185, and phosphorylated itself slowly on tyrosine, threonine and serine residues, establishing that it is a 'dual specificity' protein kinase. Peptide sequences from MAPKK were homologous to other protein serine/threonine kinases, especially to the subfamily that includes yeast protein kinases that lie upstream of yeast MAP kinase homologues in the pheromone-dependent mating pathways.
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PMID:MAP kinase kinase from rabbit skeletal muscle. A novel dual specificity enzyme showing homology to yeast protein kinases involved in pheromone-dependent signal transduction. 149 29

The MEI4 gene product is required for meiotic induction of recombination and viable spore production in the yeast Saccharomyces cerevisiae. DNA sequence analysis shows that the MEI4 gene encodes a 450-amino-acid protein bearing no homology to any previously identified protein. The MEI4 coding region is interrupted by a small intron located near the 5' end of the gene. Efficient splicing of the MEI4 transcript is not dependent on the MER1 protein, which is required for splicing the transcript of another meiotic gene, MER2. Expression of a mei4::lacZ fusion gene is meiosis-specific and depends on both heterozygosity at the mating-type locus and nutrient limitation. Northern (RNA) blot hybridization analysis suggests that MEI4 gene expression is regulated at the level of transcription. A functional MEI4 gene is not required for meiotic induction of transcription of the MER1, MER2, MEK1, RED1, SPO11, or RAD50 gene. Cytological analysis of mei4 mutant strains during meiotic prophase demonstrates that the chromosomes form long axial elements that fail to undergo synapsis. The meiosis II division is delayed in mei4 strains.
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PMID:MEI4, a meiosis-specific yeast gene required for chromosome synapsis. 154 15

Using HS.GC, We have succeeded in simultaneous determination of Ac, MeOH and MEK in urine without any complicated pretreatment or correction by internal standard. Moreover, in order to lower the detection limits of these materials, study was made on the salting out effect using 14 kinds of salts. As pretreatment, 2.0 ml of urine, 3.0 g of sodium sulfate and small sized magnetic stirrer are put into vial, which is sealed by septum. This is then heated for 10 min in warm bath of 50 degrees C. In order to dissolve the added salts as much as possible, the specimen is stirred by the stirrer. After cooling the liquid to room temperature, the specimen is analysed by HS.GC. The results showed that sodium sulfate was excellent synthetically. 1) Using the urine of workers not exposed to organic solvents three kinds of urine having specific gravity of 1.010, 1.024 and 1.034 were prepared and mixed standard organic solvents (Ac, MeOH and MEK) were added. Recovery percentages and coefficients of variation were calculated. The results showed that recovery percentages ranged from 92.0 to 101.7% and coefficients of variation from 0.2 to 4.6%. 2) The regression equations of standard curves were satisfactory with y = 9053x - 200(r = 0.999, n = 12) for Ac, y = 801x - 400 (r = 0.999, n = 12) for MeOH, and y = 15488x - 277 (r = 0.999, n = 12) for MEK. 3) The detection limits calculated by IUPAC formula were 0.0092 mg/l for Ac, 0.11 mg/l for MeOH and 0.0063 mg/l for MEK. These results indicated that this method is superior to other methods because the pretreatment is very simple, specificity is excellent, analysis by standard curves is possible, and this method is not affected by specific gravity of the urine.
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PMID:[Determination of acetone, methanol, and methyl ethyl ketone in urine using head-space gas chromatography (HS.GC)]. 161

Preparation of milligram amounts of [32P]p42mapk, phosphorylated at Tyr185 or diphosphorylated at Tyr185/Thr183, for use as specific protein phosphatase substrates is described. Tyr- but not Thr-phosphorylated p42mapk, accumulates when ATP is limiting. Furthermore, Tyr185-phosphorylated p42mapk exhibits an apparent 10-fold decrease in apparent Km (46.6 +/- 6.6 nM) for MAP kinase kinase compared to that for the dephospho form (approximately 476 nM). We conclude that Tyr185 precedes Thr183 phosphorylation, and that this is prerequisite, dramatically increasing the affinity of p42mapk for MAP kinase kinase.
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PMID:Ordered phosphorylation of p42mapk by MAP kinase kinase. 162 39

The mek1 (meiotic kinase) mutant of Saccharomyces cerevisiae was isolated in a screen for sporulation-proficient, meiotic-lethal mutants. Diploids homozygous for a mek1 null mutation produce only 13% viable spores. mek1 spore inviability is rescued by a spo13 mutation, which causes cells to bypass the meiosis I division. In a mek1 null mutant, meiotic recombination is reduced but not completely eliminated. Nuclear spreads of meiotic chromosomes from mek1 diploids reveal numerous stretches of synaptonemal complex (SC) that are shorter than wild-type SCs. Analysis of a mek1::lacZ fusion gene and Northern blot hybridization demonstrate that the MEK1 transcript is present only in meiosis. The sequence of the MEK1 gene predicts a 56.8-kD protein with homology to serine-threonine protein kinases. The MEK1 gene maps to chromosome XV, 13 cM proximal to CDC64. Models for the function of the MEK1 gene product are proposed.
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PMID:A meiosis-specific protein kinase homolog required for chromosome synapsis and recombination. 175 35

This is a report on the synthesis of hexamethyl-propylene-amine oxime (HM-PAO), a new agent for regional cerebral blood flow (gamma CBF) imaging, the separation of its diastereoisomers (dl- and meso-HM-PAO), and a comparative study of three forms of Tc- 99m labelled HM-PAO (dl-, meso- and mixture-) in chromatography, mice biodistribution and rabbit imaging. The results showed that the Rf value of Tc-99m-dl-HM-PAO (0.8-1.0) on silica G thin layer chromatography with MEK as solvent was different from that of Tc-99m-meso-HM-PAO (0.6-0.8), and that the retention of dl- isomer in the brain was higher and more static than those of meso-and mixture HM-PAO but identical with Ceretec, a dl-HM-PAO kit manufactured by Amersham Inc., England. The primary clinical applications for gamma CBF SPECT imaging demonstrated a satisfactory result.
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PMID:[Synthesis of hexamethyl propylamine oxime and comparative study of its diastereoisomers]. 177 39

Primary cultures of mouse epidermal keratinocytes from SENCAR mice were treated with 7,12-dimethylbenz(a)anthracene (DMBA), benzo(a)pyrene [B(a)P], (+/-)7 beta-8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene [(+/-)anti-BPDE], and (+/-)7 beta, 8 alpha-dihydroxy-9 beta, 10 beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene [(+/-)syn-BPDE] to examine the relationship between DNA adduct formation and the induction of unscheduled DNA synthesis (UDS). DNA adducts were measured as pmol hydrocarbon bound per mg of DNA, and UDS was quantitated autoradiographically as net grains per nucleus. A good correlation was observed between the levels of UDS detected and the amount of DNA adducts present in the cell population when comparing similar compounds within the linear dose-response range of 0.005 micrograms/ml-0.25 micrograms/ml. A higher rate of UDS for a given level of DNA adducts was interpreted as an increased efficiency of DNA repair. In some cases, an increase in the efficiency of DNA excision repair correlated with lower tumor-initiating activity. For this family of PAH, the concentration below which UDS could no longer be detected was approximately 0.01 microgram/ml. However, DNA adducts were measurable at concentrations of 0.01 and 0.005 micrograms/ml. The limits of detection of the current UDS assay in the SENCAR MEK culture system occurred at hydrocarbon adduct levels of approximately 10 pmol/mg DNA, or approximately 1 adduct per 3 x 10(5) bases. Additionally, the UDS assay was unable to detect DNA repair induced by the weakly carcinogenic PAHs, dibenz(aj)anthracene and 7-methyl-dibenz(aj)anthracene. The UDS assay did detect DNA repair by the more strongly carcinogenic PAH, 6-methylcholanthrene. These results suggest that the present UDS assay with MEKs is a useful assay for the rapid screening of potential genotoxic agents. However, the limits of sensitivity are such that the current assay may be unable to detect a low level of DNA damage induced by some weakly genotoxic (carcinogenic) agents. In addition, while the limits of sensitivity determined in these experiments apply to the polycyclic aromatic hydrocarbon class, other classes of genotoxic compounds such as alkylating agents or crosslinking agents may exhibit different thresholds of detection.
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PMID:Relationship between DNA adduct formation and unscheduled DNA synthesis (UDS) in cultured mouse epidermal keratinocytes. 191 14


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