Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatitis B surface antigen possesses the group-specific determinant called a and one or another member from each of two pairs of allelic determinants, d and y as well as w and r, thereby creating the four major subtypes, adw, adr, ayw and ayr. In the sequence of major surface antigen polypeptides made of 226 amino acid residues, lysine or arginine at amino acid position 122 specifies d or y determinant, and lysine or arginine at position 160 specifies w or r determinant, respectively. By means of site-directed mutagenesis and expression of mutant genes in cultured cells, the mechanism for the loss of subtypic determinants on surface antigens was investigated at the molecular level. A rare sample of surface antigen of subtype ad, devoid of w or r determinant, had asparagine at position 160. When it was converted to lysine, the surface antigen of subtype adw was obtained. Two samples of surface antigen were subtyped as ar. They lacked d determinant, despite having lysine at position 122 which usually specified it. They differed from all reported sequences of surface antigen in amino acid 144 or 145. They displayed d determinant when amino acid 144 was converted from glutamic acid to aspartic acid, or when amino acid 145 was changed from alanine to glycine. These results indicate that the key amino acid residue at position 122 or 160 is indispensable for the expression of subtypic determinants and that some distant residues are also crucially involved in conforming them.
Mol Immunol 1989 Feb
PMID:The loss of subtypic determinants in alleles, d/y or w/r, on hepatitis B surface antigen. 246 92

Bacillus subtilis alpha-amylase signal peptide, which consists of 33 amino acids, is functional in Escherichia coli cells. Lysine, glutamic acid, leucine, leucyl-leucine, or leucyl-leucyl-leucine was inserted between positions 28 and 29 of the alpha-amylase signal peptide using site directed mutagenesis. DNAs encoding the wild-type and modified signal peptides were then fused in-frame to DNAs encoding the mature regions of the beta-lactamase of pBR322 and a thermostable alpha-amylase. The secretion of beta-lactamase in E. coli cells was more inhibited by the modified signal peptides than that in B. subtilis cells, although the degree of inhibition varied and the inhibitory effect of each signal peptide was found to be similar in the two strains. In contrast, the difference in the inhibitory effect of each modified signal peptide was no longer detected in the case of the production of thermostable alpha-amylase, except for the insertion of glutamic acid. Nearly 50% of thermostable alpha-amylase in the precursor form was accumulated in the intracellular fraction of E. coli cells containing the DNAs for the modified signal peptides. The insertion of glutamic acid inhibited the secretion of the two enzymes in both B. subtilis and E. coli cells.
Mol Gen Genet 1989 Mar
PMID:Modification of length, hydrophobic properties and electric charge of Bacillus subtilis alpha-amylase signal peptide and their different effects on the production of secretory proteins in B. subtilis and Escherichia coli cells. 247 21

T helper cell responsiveness to some synthetic polypeptides is controlled by Ir genes. It has been suggested that the inability of class II complexes to associate with conventional soluble antigens, on the surface of antigen presenting cells, can result in a characteristic pattern of antigen-specific T cell unresponsiveness, mapping to the I region of the MHC. Alternatively, during the establishment of self-tolerance, a hiatus could be generated in the T cell repertoire, when an epitope exhibited by a conventional antigen topochemically resembled (per se or in association with a self MHC epitope) a potentially immunogenic self antigenic determinant. The synthetic polypeptide GLT offers an interesting possibility for investigating the connection between tolerance to self-MHC antigens and Ir gene controlled unresponsiveness. It has been shown that mice which do not express I-Ek possess significant numbers of T cells which aberrantly recognize GLT in the context of various allogeneic class II MHC molecules. Moreover, if T cell populations obtained from such mice are depleted of alloreactivity to I-Ek in vitro, it results in the deletion of T cell clones specific for GLT presented by several I-A and I-E molecules. These observations are compatible with the hypothesis that GLT alone can mimic an I-Ek epitope, thus being able to interact directly with some of the T-cell receptors specific for I-Ek. Experiments presented in this communication indicate that GLT specifically inhibits the proliferation in vitro of a fraction of the MLR blasts generated against I-Ek. In addition, we characterize a T cell hybrid clone specific for I-Ek which can be functionally modulated by GLT.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Immunol 1985
PMID:T cell receptor binding and unrestricted reactivity to GLT in somatic variants of an I-Ek specific T cell hybrid. 247 53

SOD-4, a cytosolic form of superoxide dismutase in maize, originally was defined as a single band of activity by zymogram analysis. The protein was purified to "homogeneity" as shown by a single band on native or denaturing polyacrylamide gels and a single spot on two dimensional gels. The N-terminal amino acid sequence for the first 20 residues was determined for the purified SOD-4 protein. All residues were clearly determined except for residue twelve, where both glutamic and aspartic acids were found. A maize lambda gt11 cDNA library was constructed from scutellar poly(A)+ RNA. Two cDNAs were isolated, restriction mapped, and their DNA sequences determined. The amino acid sequence deduced from both cDNAs matched perfectly the N-terminal sequence of the purified protein except for the residue at position 12. Significantly, at the twelfth codon, one cDNA was found to code for glutamic acid and the other cDNA had a codon for aspartic acid. Both cDNAs contained similar but not identical 5' and 3' untranslated sequences. Both cDNAs contained polyadenylation signals and tails. cDNA isolations, RNA, and genomic DNA blots confirm the existence and expression of two genes that produce indistinguishable SOD-4 proteins.
Mol Gen Genet 1989 Oct
PMID:Two cDNAs encode two nearly identical Cu/Zn superoxide dismutase proteins in maize. 248 36

The rules underlying muscarinic acetylcholine receptor (mAChR) regulation in an in vitro cortical slice preparation of adult rats were examined following various alterations of bioelectric activity and following agonist stimulation. Muscarinic ACh antagonists [3H]N-methyl scopolamine ([3H]NMS) or [3H]quinuclidinyl benzylate ([3H]QNB) were used to label cell surface vs total (i.e. surface and internal) receptors, respectively. Depolarization of neural membranes for 4 h at 22-37 degrees C using veratridine or high external potassium (K+) led to a temperature-dependent down-regulation of surface mAChR of 26.2% and 11.3%. Total mAChRs decreased by 37.6% and 8.1%. Addition of picrotoxin and glutamic acid also led to decreases in mAChRs. Increases in inward chloride ion current induced by gamma-aminobutyric acid (GABA) or gold chloride had no significant effect on mAChRs. Blockade of calcium channels and synaptic transmission by magnesium or cobalt and postsynaptic calcium channels with nifedipine showed a significant effect on mAChRs only in the latter case. In contrast, agonist stimulation using carbachol led to a large down-regulation for both [3H]NMS and [3H]QNB (26.1%, 35.9%). ACh decreased [3H]QNB binding by 33.9%, but had little effect on [3H]NMS binding (6.3%). For [3H]QNB binding sites the effects of carbachol appeared to summate with those of veratridine. Down-regulation of [3H]NMS labelled mAChRs by carbachol and veratridine had an estimated half-time of 30 min and 2 h, respectively. Neither the effects of veratridine nor carbachol could be antagonized by tetrodotoxin (TTX), showing that the effects were not due to an increase in sodium ion currents. However, a common thread linking the various agents which induce mAChR down-regulation appears to involve changes in potassium (K+) current. Potassium channel blockers tetraethylammonium chloride (TEA), 4-aminopyridine (4-AP) and apamin had little independent effect on mAChR number, but prevented veratridine-induced down-regulation, presumably through a blockade of K+- and Ca2+-dependent K+-channels. Only TEA and 4-AP diminished carbachol-induced down-regulation suggesting that this effect involves only the non Ca2+-dependent K+-channels. It thus appears that mAChR regulation in the rat cerebral cortex is linked to changes in active K+-channel currents: activation of the K+-channel by depolarization-induced changes in K+ current or by agonist stimulation leading to changes in the selective K+ currents stimulate mAChR down-regulation; blockage of the K+-channels prevents this down-regulation.
Brain Res Mol Brain Res 1989 Jan
PMID:A role for potassium channels in the regulation of cortical muscarinic acetylcholine receptors in an in vitro slice preparation. 253 5

L-Glutamate, the natural agonist of quisqualate- and N-methyl-D-aspartate (NMDA)-sensitive excitatory amino acid receptors, elicits a rapid, transient, dose-dependent increase of the steady state level of c-fos mRNA followed by an accumulation of c-fos protein immunostaining in cell nuclei. This induction is prevented by 2-amino-5-phosphonovalerate, an isosteric glutamate receptor antagonist, and by Mg2+ ion and phencyclidine, two noncompetitive allosteric antagonists of NMDA-sensitive glutamate receptors. Kainate and quisqualate (up to 150 microM) failed to alter the basal expression of c-fos mRNA. Furthermore, glycine, a positive allosteric modulator of NMDA-sensitive glutamate receptors, potentiated the glutamate response in a strychnine-insensitive manner. Activation of other transmitter receptors present in these cells (gamma-aminobutyric acid(A), gamma-aminobutyric acid(B), and muscarinic) failed to increase c-fos mRNA expression. Our results provide evidence that activation of NMDA-sensitive glutamate receptors plays an exclusive role in the induction of c-fos mRNA expression and translation in primary cultures of granule cells. It can be inferred that, by this mechanism, glutamate can initiate a transcriptional program that may result in changes in the simultaneous expression of a set of target genes involved in neuron-specific responses.
Mol Pharmacol 1989 Apr
PMID:In primary cultures of cerebellar granule cells the activation of N-methyl-D-aspartate-sensitive glutamate receptors induces c-fos mRNA expression. 253 55

1. L-Glutamate, the most likely transmitter of rapid excitatory synaptic interactions in the brain and spinal cord, is a potent neurotoxin. Mechanisms that terminate the action of glutamate are, therefore, likely to be important for maintaining the integrity of glutaminoceptive neurons. In this study, we show that glutamate currents evoked in voltage-clamped chick motoneurons fade during prolonged or repeated application of glutamate by pressure ejection from nearby pipettes. 2. The magnitude of the decline depends on the Ca2+/Mg2+ ratio in the extracellular medium. With Ca2+ = 10.0 mM and no added Mg, the steady-state glutamate current amounted to 50% of the initial value. 3. Single-channel measurements indicate that the fade is due to receptor desensitization rather than to agonist-induced channel blockade, as the mean channel open time within bursts is independent of the agonist concentration. 4. Application of more selective agonists showed that Ca2+-dependent slow desensitization involved only G1 (NMDA) receptors. G2 responses (activated by kainate and quisqualate) did not exhibit this slow phase of desensitization under the same conditions.
Cell Mol Neurobiol 1989 Mar
PMID:Calcium-dependent, slow desensitization distinguishes different types of glutamate receptors. 254 Sep 13

The chemotactic properties of a number of Azospirillum brasilense natural strains have been studied. Azospirillum demonstrate the positive chemotactic reaction towards the organic acids salts but a poor reaction towards the presence of the attractants like hydrocarbons and aminoacids except for arabinose and glutamic acid. The series of Che- mutants deficient in general chemotaxis has been selected by introducing the transposon Tn5 into the cells of rifampicinresistant mutant strain Azospirillum brasilense 5T-2. The ability of the mutant cells to fast and solid adsorption on the roots of the sterile wheat sprouts is shown to be decreased 2-3 folds as compared with the one of the wild type strain. Chemotaxis is suggested to affect the adsorbtion ability of azospirillum and their associative properties.
Mol Gen Mikrobiol Virusol 1989 Apr
PMID:[The role of chemotaxis genes in establishing the associative relations between Azospirillum brasilense and wheat]. 254 68

HOE 15030 inhibited the growth of BHK cells at concentrations that did not inhibit their nuclear DNA and RNA syntheses. When BHK cells were cultured in the presence of 30 micrograms/ml of HOE 15030, cells were arrested in the G1 phase after one or two cell divisions. After removal of the drug, cells progressed through the G1 to the S phase. HOE 15030 inhibited the activities of both topoisomerases I and II in vitro. To determine the target molecule of HOE 15030 in cells, we isolated a HOE 15030-resistant (HOEr) mutant of BHK cells. The HOEr cells exhibited cross-resistance to ethidium bromide, acriflavine, and rhodamine 123, and slight cross-resistance to 4'-dimethylepipodophyllotoxin-4-(4,6-O-ethylidine-beta-D-glu copyranoside) (VP-16) and adriamycin, but not to chloramphenicol, oligomycin, novobiocin, colchicine, or vinblastine. The uptake and retention of rhodamine 123 by HOEr cells were lower than those by BHK cells. Mitochondrial DNA synthesis of HOEr cells was more resistant to HOE 15030 and ethidium bromide than that of wild-type cells. These results indicate that the resistance of HOEr cells to drugs is due to reduced uptake or accumulation of the drugs by mitochondria and suggest that the mitochondria are the main target of HOE 15030 in cells.
Somat Cell Mol Genet 1989 Jul
PMID:Biochemical and genetic analysis of toxic effect of HOE 15030 in mammalian cells. 254 91

An N-terminal deletion mutant of preproparathyroid hormone that contains a single basic amino acid, lysine, in the N-terminal domain of the signal peptide is translocated across the endoplasmic reticulum membrane similarly to intact preproparathyroid hormone. To examine the function of charged residues preceeding the hydrophobic core, the lysine was replaced by an uncharged (methionine) or negatively charged (glutamic acid) amino acid. The translocational activity of the mutant signal peptides was assayed in a reticulocyte lysate system containing chicken oviduct microsomal membranes. Altering the net charge of the N-terminal domain did not abolish signal sequence activity, although the efficiency of translocation was decreased for the mutant with a glutamic acid substitution. Posttranslational, ribosome independent, translocation was observed for all the mutants tested, with the same dependence on N-terminal charge but with much lower efficiency than cotranslational translocation. These studies show that the presence of basic amino acids in the N-terminal domain of a eukaryotic signal sequence is not required for its activity.
Mol Endocrinol 1989 Jan
PMID:N-terminal basic amino acids are not required for translocation and processing of preproparathyroid hormone. 256 67


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