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)

The mutation causing cystic fibrosis (CF) has been localized to the DNA sequence of 700 kb bounded by the loci identified by the markers pMP6d-9 (D7S399) and pJ3.11 (D7S8). A 560-kb fragment obtained after SacII digestion of DNA from a cell line containing this region of human chromosome 7 in a mouse background was separated using pulse-field gel electrophoresis and isolated from the gel. The DNA was digested with BamHI prior to cloning into lambda EMBL3. Approximately 0.1% of the resulting clones contained human repetitive sequences, and 24 such recombinants were studied. Of these, 23 are on chromosome 7; 8 clones were duplicated, and of the 15 different recombinants, 7 are between MET and INT1L1, and a further 7 are between INT1L1 and pMP6d-9, leaving a single marker, pG2, which is between pMP6d-9 and pJ3.11. pG2 recognizes an RFLP with XbaI. A cosmid walk from pG2 has generated a further marker, H80, which recognizes an RFLP with PstI. This new locus (D7S411) divides the remaining region between the CF flanking markers, thereby making it more accessible to fine pulse-field mapping and allowing the precise localization of further clones to this region. Although it is not possible to position the CF locus unequivocally with respect to D7S411, both polymorphic markers at this locus exhibit low but significant linkage disequilibrium with CF, placing the emphasis for the search for the gene on the D7S399 to D7S411 interval of 250 kb.
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PMID:A new polymorphic locus, D7S411, isolated by cloning from preparative pulse-field gels is close to the mutation causing cystic fibrosis. 196 45

In order to assess the roles of central adrenoceptors in the release of atrial natriuretic peptide (ANP), aldosterone (ALD), vasopressin (AVP) and renin as well as in the regulation of renal and cardiovascular functions, either norepinephrine (NE; 0.07 microgram/kg/min), guanabenz (GB; alpha 2-agonist; 0.4 microgram/kg/min), methoxamine (MET; alpha 1-agonist; 0.4 microgram/kg/min), or isoproterenol (ISO; beta-agonist; 0.07 microgram/kg/min), dissolved in the artificial cerebrospinal fluid (ACSF), was intracerebroventricularly (i.c.v.) administered at a rate of 10 microliters/min for 30 min in anesthetized dogs. In the control study, the drugs were omitted. NE decreased mean arterial pressure (MAP), urinary osmolality (Uosm) and plasma ALD and AVP concentrations, and increased urine flow (UF). GB increased UF and urinary K excretion without any changes in urinary Na excretion, but decreased plasma ALD and AVP, heart rate, and Uosm without changes in MAP. ISO decreased MAP and plasma ALD, and increased Na and K output, renal plasma flow and UF with decreased Uosm. MET and ACSF failed to affect any of these parameters. Glomerular filtration rate, plasma ANP concentration and renin activity did not change in any of the studies. The present results suggest that central alpha 2- and beta-adrenoceptors may attenuate ALD and/or AVP release without changes in ANP and renin release, and decrease blood pressure, thereby causing a diuresis and natriuresis.
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PMID:Effects of intracerebroventricular administration of adrenoceptor-agonists on the regulation of renal water and electrolytes handling through endocrine, renal and hemodynamic function. 198 17

Many malignancies exhibit distinct patterns of metastasis that appear to be mediated by receptor/ligand-like interactions between tumor cells and organ-specific vascular endothelium. In order to study endothelial cell surface molecules involved in the binding of metastatic cells, we developed a perfusion method to isolate outside-out membrane vesicles from the lumenal surface of rat lung microvascular endothelium. Lungs were perfused in situ for 4 h at 37 degrees C with a solution of 100 mM formaldehyde, 2 mM dithiothreitol in phosphate-buffered saline to induce endothelial cell vesiculation. Radioiodinated rat lung endothelial cell membrane vesicles bound lung-metastatic tumor cells (B16F10, R323OAC-MET) in significantly higher numbers than their low or nonmetastatic counterparts (B16F0, R323OAC-LR). In contrast, leg endothelial membrane vesicle showed no binding preference for either cell line. Neuraminidase treatment of vesicles abolished specificity of adhesion of lung-derived vesicles to lung metastatic tumor cells. These results demonstrate that in situ perfusion is an appropriate technique to obtain pure endothelial cell membrane vesicles containing functionally active adhesion molecules. The preferential binding of lung-derived endothelial cell membrane vesicles by lung metastatic tumor cells is evidence of the importance of endothelial cell adhesion molecules in the formation of metastases.
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PMID:Endothelial cell membrane vesicles in the study of organ preference of metastasis. 198

Protein tyrosine kinases are crucially involved in the control of cell proliferation. Therefore, the regulation of their activity in both normal and neoplastic cells has been under intense scrutiny. The product of the MET oncogene is a transmembrane receptorlike tyrosine kinase with a unique disulfide-linked heterodimeric structure. Here we show that the tyrosine kinase activity of the MET-encoded protein is powerfully activated by tyrosine autophosphorylation. The enhancement of activity was quantitated with a phosphorylation assay of exogenous substrates. It involved an increase in the Vmax of the enzyme-catalyzed phosphotransfer reaction. No change was observed in the Km (substrate). A causal relationship between tyrosine autophosphorylation and activation of the kinase activity was proved by (i) the kinetic agreement between autophosphorylation and kinase activation, (ii) the overlapping dose-response relationship for ATP, (iii) the specificity for ATP of the activation process, (iv) the phosphorylation of tyrosine residues only, in the Met protein, in the activation step, (v) the linear dependence of the activation from the input of enzyme assayed, and (vi) the reversal of the active state by phosphatase treatment. Autophosphorylation occurred predominantly on a single tryptic peptide, most likely via an intermolecular reaction. The structural features responsible for this positive modulation of kinase activity were all contained in the 45-kDa intracellular moiety of the Met protein.
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PMID:The tyrosine kinase encoded by the MET proto-oncogene is activated by autophosphorylation. 200 82

RELP analysis of DNA loci MET, D7S8 and D7S23 was carried out in Leningrad population and partially in populations of Moscow, Azerbaijan, Ukraine, Buryatia as well as in individuals from high risk families and in cystic fibrosis (CF) patients by means of blot hybridization and polymerase chain reaction. Allelic polymorphism of all loci studied in these three groups was found to be quite similar to that in the North-Western Europe and in whites of the North America. Linkage disequilibrium of the alleles studied with the CF gene was especially pronounced for alleles of the D7S23 locus and gradually decreases from KM-19 through CS-7 to XV-2c DNA probes. The data witness genetic homogeneity of the CF mutation in European populations of the USSR and its similarity to this mutation in Western Europe. The significance of these data for potential diagnosis of CF and for heterozygous carrier detection is discussed.
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PMID:[Allele polymorphism of the DNA loci MET, D7S8, D7S23, linked to the cystic fibrosis gene in some populations of the USSR, in high risk families and in cystic fibrosis patients]. 203 48

The TPR-MET oncogenic rearrangement was originally observed in an in vitro transformed human osteosarcoma cell line. Recently, we detected the expression of this rearrangement at very low levels in several cell lines derived from human tumors of nonhematopoietic origin using a highly sensitive method based on polymerase chain reaction amplification of the transcript. We report here the results of analysis of TPR-MET expression in cell lines derived from human gastric tumors and 22 biopsy samples of human gastric mucosa showing cancer or precursor lesions. The rearranged RNA was expressed in all four cell lines as well as in biopsy samples from 12 of the 22 patients. Overexpression of TPR-MET RNA in superficial gastritis lesions with hyperplasia of glandular neck cells suggests the possible involvement of this oncogene at an early stage of gastric tumorigenesis. Analysis of gastric biopsy samples for RAS gene mutations showed base substitutions occurring in the codon 12 region of Ki- and Ha-RAS genes in four cases, including two precursor lesions.
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PMID:The TPR-MET oncogenic rearrangement is present and expressed in human gastric carcinoma and precursor lesions. 205 72

After acclimation to 100, 75 and 50% of Sea Water (SW) external salinities, a significant reduction in MET (Mean Epithelial Thickness) and MDR (Mean Diverticular Radius) indicates a decrease in the digestive cell volume dependant on the lowering of environmental salinity. The interstitial connective tissue seems to be unable to osmoregulate and hence stand severe changes in cell size depending on external salinity. 50% SW acclimated periwinkles show a general pattern of general stress response (decreasing MET and MDR, and increasing ND -Numerical Density of lysosomes- and lysosomal size). A reduction in number and size of digestive lysosomes in winkles acclimated to 75% of Sea Water evidences the functioning of regulatory mechanism of digestive cell volume.
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PMID:Responses of winkles digestive cells and their lysosomal system to environmental salinity changes. 205 84

The Raman microprobe technique was applied for analysis of the molecular components at the adhesive interface between 4-META/MMA-TBB resin and dentin. The Raman spectra showed that the 4-META molecules in monomer solution were mostly hydrolyzed into 4-MET molecules, which were then co-polymerized with MMA molecules to form resin and resin-reinforced dentin layers. On the basis of line analysis by the Raman microprobe, resin molecules were estimated to penetrate 6 microns into the dentin from the interface. Raman intensity studies indicated that the concentration of 4-MET molecular units in the resin-reinforced dentin was more than four times the concentration in the original monomer solution. This demonstrated the excellent infiltration ability of 4-MET monomer into dentin substrate in situ.
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PMID:Vibrational analysis by Raman spectroscopy of the interface between dental adhesive resin and dentin. 206 92

Adhesion of a composite to tooth substrates was studied. The bonding liner was a mixture: camphorquinone, 0.5%; one of four sulfonamides (A, B, C, and D), 0.5%; 4-methacryloxyethyl trimellitate (4-MET), 0, 2, and 5%; in triethyleneglycol dimethacrylate (TEGDMA). The best tensile bond strength to bovine dentin treated with 0.3 M EDTA 2 Na-0.2 M EDTA FeNa (EDTA 3-2) was 7.5 MPa. The bond strength to bovine dentin decreased with the addition of 4-MET. The bond strength to bovine enamel treated with 65% phosphoric acid (H3PO4) was 12.0 MPa. The tensile bond strength to bovine enamel treated with EDTA 3-2 was lower than that to enamel treated with 10% citric acid-3% ferric chloride (10-3) and with H3PO4. The polymerization of these liners was characterized by differential scanning calorimetry (DSC). The photocurable bonding liner studied was adequate for clinical studies.
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PMID:Effect of sulfonamides and 4-MET on adhesion to tooth substrates. 212 55

Effect of adhesion promoting monomers dissolved in photocurable bonding agents on adhesion to ground dentin was investigated. They were MDP, Phosmer-M and 4-MET. The effect of those monomers was compared with that of Phenyl-P. The bonding agents contained campherquinone (CQ) as a photosensitizer, N-phenylglycine (NPG) as a reducing agent and TEGDMA as a base monomer. Phenyl-P was the best adhesion promoting monomer among those studied monomers. MDP could not polymerize well enough to give good bond strength. Phosmer-M could permeate through the smeared layer but could not make a stable resin reinforced dentin. 4-MET did not permeate through the smeared layer and did not adhere to ground dentin.
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PMID:[Effect of adhesion promoting monomers on adhesion to ground dentin]. 213 54


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