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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. In voltage-clamp experiments on frog myelinated nerve fibers, the effects of nine synthetic derivatives of batrachotoxin (BTX) obtained from 7,8-dihydrobatrachotoxinin A (DBTX-A) on Na+ currents (INa) have been investigated. 2. Both of 20 alpha-esters of DBTX-A with 2,4,5-trimethylpyrrol-3-carboxylic acid (DBTX-P) and benzoic acid (DBTX) at a 10(-5) M concentration caused modification of INa qualitatively similar to that induced by BTX. 3. The quaternary derivative of DBTX (QDBTX) produced such changes in INa only at a 5.10(-4) M concentration, apparently due to its much lower lipid solubility. 4. Replacement of a -CH2- by a -C = O. group in the homomorpholine ring near the tertiary nitrogen atom abolished the DBTX activity, strongly suggesting the necessity of tertiary nitrogen protonation for the toxin interaction with the channel receptor. 5. Transfer of an 11-hydroxygroup from the alpha- to the beta-position in the DBTX molecule did not decrease its activity in spite of the fact that in the beta-position this group is sterically very hindered. The activity of 11 beta-DBTX is at variance with the prediction of Codding's (1983) "oxygen triad" hypothesis. 6. DBTX-A and compounds obtained from DBTX by oxidation of the 11 alpha-hydroxygroup (K-DBTX), acetylation (Ac-DBTX), or reduction of the hemiketal moiety (H2DBTX) even at a concentration as high as 10(-3) M were able to modify only a very small fraction of the Na channels. However, a clear-cut reversible blocking action on both normal and modified Na channels was observed. 7. These results led us to conclude that BTX modifies the Na channels only in the charged form and hemiketal and 20 alpha-ester moieties provide adequate disposition of toxin on the receptor surface. The inability of H2DBTX, DBTX-A, and K-DBTX and Ac-DBTX to modify most of the Na channels can be explained by a low "probability of correct disposition" of these ligands on the receptor surface.
Cell Mol Neurobiol 1992 Feb
PMID:Comparative analysis of the effects of synthetic derivatives of batrachotoxin on sodium currents in frog node of Ranvier. 131 17

Schizosaccharomyces pombe initiates sexual development in response to nutritional starvation. The level of cAMP in S. pombe cells changed during the transition from exponential growth to stationary phase. It also changed in response to a shift from nitrogen-rich medium to nitrogen-free medium. A decrease of approximately 50% was observed in either case, suggesting that S. pombe cells contain less cAMP when they initiate sexual development. S. pombe cells that expressed the catalytic domain of Saccharomyces cerevisiae adenylyl cyclase from the S. pombe adh1 promoter contained 5 times as much cAMP as the wild type and could not initiate mating and meiosis. These observations, together with previous findings that exogenously added cAMP inhibits mating and meiosis and that cells with little cAMP are highly derepressed for sexual development, strongly suggest that cAMP functions as a key regulator of sexual development in S. pombe. The pde1 gene, which encodes a protein homologous to S. cerevisiae cAMP phosphodiesterase I, was isolated as a multicopy suppressor of the sterility caused by a high cAMP level. Disruption of pde1 made S. pombe cells partially sterile and meiosis-deficient, indicating that this cAMP phosphodiesterase plays an important role in balancing the cAMP level in vivo.
Mol Gen Genet 1992 May
PMID:Reduction in the intracellular cAMP level triggers initiation of sexual development in fission yeast. 131 97

Four starvation-inducible loci (stiA, stiB, stiC, and stiE) of Salmonella typhimurium have been extensively characterized as to their genetic and physiologic regulation, and their roles in survival during prolonged simultaneous phosphate (P)-, carbon (C)- and nitrogen (N)-starvation (PCN-starvation). Strains of S. typhimurium LT-2, isogenic with the exception of lacking either the stiA, stiB or stiC locus, died off more quickly and survived at much reduced levels compared with their wild-type parent. When certain sti mutations were combined in the same strain, we found that viability of these cultures declined even more rapidly, and starvation-survival was affected to levels over-and-above the additive effects of each individual mutation, indicating an epistatic relationship between these loci. All four sti loci were, directly or indirectly, under negative control by the crp gene product (cAMP receptor protein, CRP). With the exception of stiB, all were similarly regulated by the cya gene product (i.e., cAMP). This suggests that CRP acts alone, or with a signal molecule other than cAMP, to cause repression of the stiB locus. In addition, all four loci are under positive regulation by the relA gene product (i.e., ppGpp) during C- or N-starvation, but not P-starvation. Since not all relA-dependent sti loci are induced during both C- and N-starvation, we propose that two separate ppGpp-dependent pathways function during C-starvation and N-starvation, respectively. Possible models for separate P-, C- and N-starvation-induction pathways are discussed.
Mol Microbiol 1992 Jun
PMID:Starvation-inducible loci of Salmonella typhimurium: regulation and roles in starvation-survival. 132 Jul 26

Previously, we have shown that the Saccharomyces cerevisiae DNA-binding protein ABF1 exists in at least two different electrophoretic forms (K. S. Sweder, P. R. Rhode, and J. L. Campbell, J. Biol. Chem. 263: 17270-17277, 1988). In this report, we show that these forms represent different states of phosphorylation of ABF1 and that at least four different phosphorylation states can be resolved electrophoretically. The ratios of these states to one another differ according to growth conditions and carbon source. Phosphorylation of ABF1 is therefore a regulated process. In nitrogen-starved cells or in cells grown on nonfermentable carbon sources (e.g., lactate), phosphorylated forms predominate, while in cells grown on fermentable carbon sources (e.g., glucose), dephosphorylated forms are enriched. The phosphorylation pattern is affected by mutations in the SNF1-SSN6 pathway, which is involved in glucose repression-depression. Whereas a functional SNF1 gene, which encodes a protein kinase, is not required for the phosphorylation of ABF1, a functional SSN6 gene is required for itsd ephosphorylation. The phosphorylation patterns that we have observed correlate with the regulation of a specific target gene, COX6, which encodes subunit VI of cytochrome c oxidase. Transcription of COX6 is repressed by growth in medium containing a fermentable carbon source and is derepressed by growth in medium containing a nonfermentable carbon source. COX6 repression-derepression is under the control of the SNF1-SSN6 pathway. This carbon source regulation is exerted through domain 1, a region of the upstream activation sequence UAS6 that binds ABF1 (J. D. Trawick, N. Kraut, F. Simon, and R. O. Poyton, Mol. Cell Biol. 12:2302-2314, 1992). We show that the greater the phosphorylation of ABF1, the greater the transcription of COX6. Furthermore, the ABF1-containing protein-DNA complexes formed at domain 1 differ according to the phosphorylation state of ABF1 and the carbon source on which the cells were grown. From these findings, we propose that the phosphorylation of ABF1 is involved in glucose repression-derepression of COX6 transcription.
Mol Cell Biol 1992 Sep
PMID:ABF1 is a phosphoprotein and plays a role in carbon source control of COX6 transcription in Saccharomyces cerevisiae. 132 16

To facilitate genetic analyses of Rhizobium meliloti genes that are involved in symbiosis, we determined the map positions of 11 symbiotic loci on the R. meliloti chromosome by using a combination of the Tn5-Mob conjugational transfer method described by Klein et al. (S. Klein, K. Lohmann, G. C. Walker, and E. R. Signer. J. Bacteriol. 174:324-326, 1992) and co-transduction of genetic markers by bacteriophage phi M12. Loci involved in effective nodule formation (fix-379, fix-382, fix-383, fix-385, and fix-388), polysaccharide synthesis (exoR, exoS, exoC, and ndvB), nodule invasion (exoD), and nitrogen regulation (ntrA) were ordered with respect to previously mapped markers and each other. The positions of two other loci, degP and pho-1, were also determined.
Mol Plant Microbe Interact
PMID:Genetic mapping of symbiotic loci on the Rhizobium meliloti chromosome. 133 89

The new discipline of molecular pathology requires that high-quality, intact genomic DNA, mRNA, and proteins be available from frozen tissue samples. It is now necessary for pathology laboratories to establish consistent guidelines for the preparation and storage of frozen tissue samples in order to have properly preserved tissues available for diagnostic molecular techniques. Maintaining a frozen tissue bank requires a pathologist to oversee this program and to integrate it into the routine surgical pathology activities. A member of the laboratory technical staff can serve as a tissue bank coordinator and have responsibility for preparation of tissue samples, their systematic storage and retrieval, and routine maintenance of equipment and supplies. Tissue sampling must be done as soon as possible after excision of the specimen and is the responsibility of a qualified pathologist. The samples may be snap frozen without cryoprotection at -78 degrees C or colder for subsequent use in procedures requiring the extraction of genomic DNA, mRNA, or protein. To preserve tissue architecture and cytologic features for immunohistochemistry and in situ hybridization, the tissue should be frozen at -78 degrees C or colder with a cryoprotectant such as OCT. Long-term storage of the frozen tissue is recommended at -140 degrees C or colder in a locked liquid nitrogen freezer, and the record of sample inventory can easily be kept in a computerized database. Tissues sampled and stored under these conditions have been used successfully in a wide variety of molecular techniques. In addition to malignant tumor tissue, samples from benign lesions and normal tissues should be frozen.(ABSTRACT TRUNCATED AT 250 WORDS)
Diagn Mol Pathol 1992 Mar
PMID:Role of the frozen tissue bank in molecular pathology. 134 56

In vivo dimethyl sulfate footprinting of the Bacillus subtilis glnRA regulatory region under repressing and derepressing conditions demonstrated that the GlnR protein, encoded by glnR, interacts with two sites situated within and adjacent to the glnRA promoter. One site, glnRAo1, between positions -40 and -60 relative to the start point of transcription, is a 21-bp symmetrical element that has been identified as essential for glnRA regulation (H. J. Schreier, C. A. Rostkowski, J. F. Nomellini, and K. D. Hirschi, J. Mol. Biol. 220:241-253, 1991). The second site, glnRAo2, is a quasisymmetrical element having partial homology to glnRAo1 and is located within the promoter between positions -17 and -37. The symmetry and extent of modifications observed for each site during repression and derepression indicated that GlnR interacts with the glnRA regulatory region by binding to both sites in approximately the same manner. Experiments using potassium permanganate to probe open complex formation by RNA polymerase demonstrated that transcriptional initiation is inhibited by GlnR. Furthermore, distortion of the DNA helix within glnRAo2 occurred upon GlnR binding. While glutamine synthetase, encoded by glnA, has been implicated in controlling glnRA expression, analyses with dimethyl sulfate and potassium permanganate ruled out a role for glutamine synthetase in directly influencing transcription by binding to operator and promoter regions. Our results suggested that inhibition of transcription from the glnRA promoter involves GlnR occupancy at both glnRAo1 and glnRAo2. In addition, modification of bases within the glnRAo2 operator indicated that control of glnRA expression under nitrogen-limiting (derepressing) conditions included the involvement of a factor(s) other than GlnR.
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PMID:Interaction of the Bacillus subtilis glnRA repressor with operator and promoter sequences in vivo. 134 63

Low-frequency restriction fragment analysis of more than 100 strains of the genus Frankia showed that restriction enzyme DraI (recognition site, TTT'AAA) gave rise to large DNA fragments (200 to 1,500 kb), which, when they were subjected to cluster analysis, reflected the host plants from which the strains were isolated. Our results support the conclusions of Lalonde and his colleagues (M. Lalonde, L. Simon, J. Bousquet, and A. Seguin, p. 671-680, in H. Bothe, F. J. de Bruijn, and W. E. Newton, ed., Nitrogen Fixation: Hundred Years After, 1988; P. Normand, P. Simonet, and R. Bardin, Mol. Gen. Genet. 213:238-246, 1988) and Fernandez et al. (M. P. Fernandez, H. Meugnier, P. A. D. Grimont, and R. Bardin, Int. J. Syst. Bacteriol. 39:424-429, 1989) that various biochemical and genomic analyses can give rise to groupings of Frankia strains that are consistent with the host plants from which the strains are isolated and that the resulting groups may form a basis for defining Frankia species.
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PMID:Low-frequency restriction fragment analysis of Frankia strains (Actinomycetales). 135 77

Glutamine synthetase (GS; EC 6.3.1.2) is present in different subcellular compartments in plants. It is located in the cytoplasm in root and root nodules while generally present in the chloroplasts in leaves. The expression of GS gene(s) is enhanced in root nodules and in soybean roots treated with ammonia. We have isolated four genes encoding subunits of cytosolic GS from soybean (Glycine max L. cv. Prize). Promoter analysis of one of these genes (GS15) showed that it is expressed in a root-specific manner in transgenic tobacco and Lotus corniculatus, but is induced by ammonia only in the legume background. Making the GS15 gene expression constitutive by fusion with the CaMV-35S promoter led to the expression of GS in the leaves of transgenic tobacco plants. The soybean GS was functional and was located in the cytoplasm in tobacco leaves where this enzyme is not normally present. Forcing this change in the location of GS caused concomitant induction of the mRNA for a native cytosolic GS in the leaves of transgenic tobacco. Shifting the subcellular location of GS in transgenic plants apparently altered the nitrogen metabolism and forced the induction in leaves of a native GS gene encoding a cytosolic enzyme. The latter is normally expressed only in the root tissue of tobacco. This phenomenon may suggest a hitherto uncharacterized metabolic control on the expression of certain genes in plants.
Plant Mol Biol 1992 Oct
PMID:Forcing expression of a soybean root glutamine synthetase gene in tobacco leaves induces a native gene encoding cytosolic enzyme. 135 1

The cloning and sequence determination is reported of the DNA region of Rhizobium leguminosarum coding for glutamine synthetase II (GSII). An open reading frame (ORF) encoding 326 amino acids was defined as the glnII gene on the basis of its similarity to other glnII genes and the ability of a DNA fragment carrying this ORF to complement the glutamine auxotrophy of a Klebsiella pneumoniae glnA mutant. We find that the glnII gene in R. leguminosarum is transcribed as a monocistronic unit from a single promoter, which shows structural features characteristic of rpoN (ntrA)-dependent promoters. In K. pneumoniae, such promoters require the ntrC and rpoN (ntrA) gene products for transcription. The intracellular level of glnII mRNA changes when R. leguminosarum is grown on different nitrogen sources, as expected for regulation by the nitrogen regulatory system. Promoter deletion analysis has shown that an extensive upstream DNA sequence (316 bp) is essential for in vivo activation of the glnII promoter in different biovars of R. leguminosarum. This DNA region requires a wild-type ntrC gene for activity and includes two conserved putative NtrC-binding site sequences. The results conclusively show that transcription from the R. leguminosarum glnII promoter is fully dependent on positive control by NtrC protein and on an upstream activator sequence (UAS).
Mol Gen Genet 1992 Sep
PMID:Activation of the Rhizobium leguminosarum glnII gene by NtrC is dependent on upstream DNA sequences. 135 39


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