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)

A new human acute lymphoblastic leukemia (ALL) cell line, designated HBL-3, was established from the bone marrow of a patient with non-T-ALL. The HBL-3 cell line expressed B4 (CD 19), BA-1 (CD 24) and HLA-DR antigens, but not surface immunoglobulin (SIg) or cytoplasmic immunoglobulin (CIg). The cell line lacked the common acute lymphoblastic leukemia antigen (CALLA) and antigenic markers characteristic of T-cell and myeloid cell lineages. The HBL-3 cells had structural rearrangements of both the homologous chromosome 9s, including a translocation with chromosome 1 which has been reported in a patient with common ALL. The cell line had rearranged immunoglobulin heavy chain genes but retained germ-line kappa light chain genes and germ-line T-cell receptor beta- and gamma-chain genes. The HBL-3 cell line was strongly positive for terminal deoxynucleotidyl transferase (TdT). These findings indicate that the HBL-3 cell line is derived from the earliest B-cell committed to B-cell lineage.
Virchows Arch B Cell Pathol Incl Mol Pathol 1990
PMID:A newly established human acute lymphoblastic leukemia cell line with characteristics of the earliest B-cell maturation. 197 32

The penicillin-binding protein 4 (PBP4), from Escherichia coli, a DD-carboxypeptidase/DD-endopeptidase, was purified in an enzymatically active form to homogeneity by affinity chromatography on 6-aminopenicillanic acid/Sepharose and heparin/Sepharose. Polyclonal antibodies raised against the pure protein were used to identify and isolate PBP4 overproducing clones from an E. coli expression library, which was established on the basis of a temperature-inducible runaway replication plasmid. Three positive clones were isolated, one of which carried the intact structural gene dacB that codes for PBP4, on a 1.9kb SmaI-EcoRI fragment, whereas the other two carried truncated forms of this gene. The direction of transcription was determined. The PBP4 overproducing strain, when grown in rich medium, tolerated 160-fold overexpression. After disrupting cells by sonication, the majority (80%) of the overproduced PBP4 was detected in the 100,000 X g supernatant. Southern blotting analysis using the cloned dacB gene as a probe revealed that, in contrast to that described by Takeda et al. (1981), the plasmid pLC18-38 of the Clarke-Carbon collection does not code for PBP4. The overall composition of murein, synthesized in vitro or in vivo by the PBP4 overproducing strain, as determined by high-performance liquid chromatography analysis, suggests that PBP4 is not involved in transpeptidation but exclusively catalyses a DD-carboxypeptidase and DD-endopeptidase reaction.
Mol Microbiol 1991 Mar
PMID:Penicillin-binding protein 4 of Escherichia coli: molecular cloning of the dacB gene, controlled overexpression, and alterations in murein composition. 204 51

A cDNA copy of the M2 dsRNA encoding the K2 killer toxin of Saccharomyces cerevisiae was expressed in yeast using the yeast ADH1 promoter. This construct produced K2-specific killing and immunity functions. Efficient K2-specific killing was dependent on the action of the KEX2 endopeptidase and the KEX1 carboxypeptidase, while K2-specific immunity was independent of these proteases. Comparison of the K2 toxin sequence with that of the K1 toxin sequence shows that although they share a common processing pathway and are both encoded by cytoplasmic dsRNAs of similar basic structure, the two toxins are very different at the primary sequence level. Site-specific mutagenesis of the cDNA gene establishes that one of the two potential KEX2 cleavage sites is critical for toxin action but not for immunity. Immunity was reduced by an insertion of two amino acids in the hydrophobic amino-terminal region which left toxin activity intact, indicating an independence of toxin action and immunity.
Mol Gen Genet 1991 May
PMID:Expression in yeast of a cDNA copy of the K2 killer toxin gene. 204 53

N-Methyl-N-nitrosourea (MNU)-induced rat mammary adenocarcinomas contain high levels of a novel leupeptin-sensitive serine endopeptidase. Its properties apparently differ from those of other similar endopeptidases reported to be present in various normal and malignant mammalian tissues. The same leupeptinsensitive serine endopeptidase was also detected in normal rat mammary tissues, but at levels approximately 20 times lower than those in MNU-induced mammary tumors. This enzyme, which is a trypsin-like serine endopeptidase, preferentially hydrolyzes various synthetic endopeptidase substrates at the carboxyl side of an arginyl residue. It has an apparent Mr of approximately 160,000 and a Stokes radius of 49 A, as determined by gel filtration. Its isoelectric points range from 4.5 to 4.8, and it has a pH optimum of approximately 7.0. The enzyme is stable from pH 4.0 to 7.0, but is extremely unstable above pH 7.0. Besides leupeptin, its activity is inhibited by antipain, aprotinin, N alpha-p-tosyl-L-lysine chloromethyl ketone and phenylmethylsulfonyl fluoride, but is not inhibited by soybean trypsin inhibitor. Many other potential inhibitors or activators such as 2-mercaptoethanol, p-hydroxymercuribenzoic acid and EDTA have no effect on its activity. The enzyme is adsorbed to p-aminobenzamidine agarose affinity beads at pH 6.5 and elutes at pH 4.0.
Mol Cell Biochem 1990 Apr 18
PMID:A novel leupeptin-sensitive serine endopeptidase present in normal and malignant rat mammary tissues. 216 30

In order to assess changes in enkephalin release and biosynthesis, the levels of the tripeptide Tyr-Gly-Gly (YGG), a characteristic extracellular metabolite of enkephalins, and of the proenkephalin mRNA in mouse striatum were evaluated after a single administration of GABAergic agents. Significant and long-lasting decreases in steady state YGG levels were elicited by muscimol, a gamma-aminobutyric acid-A (GABAA) receptor agonist, diazepam, a benzodiazepine receptor agonist, or aminooxyacetic acid, a GABA-transaminase inhibitor. In addition, muscimol offset the elevation of striatal YGG elicited by bestatin, an aminopeptidase inhibitor, which entirely drives the released enkephalins into the metabolic pathway operated by enkephalinase (EC 3.4.24.11). Diazepam potentiated the effect of muscimol so that the YGG decrease induced by the combination of these two drugs was maximal after 30 min (-60%) and still significant (-40%) after 6 h, this potentiation being antagonized by pre-treatment with Ro 15-1788, a specific benzodiazepine receptor antagonist. By contrast [Met5]enkephalin steady-state levels were marginally affected by GABAergic agents, being only slightly reduced 6 h after the combination of muscimol and diazepam. After 3 h the same treatment also reduced by about 30% the level of proenkephalin mRNA, this change being maximal after 6 h (-45%) and still present after 24 h. These compared changes in various indexes of enkephalin neuron activity suggest that stimulation of GABAA receptors depresses enkephalin release immediately and for several hours, whereas preproenkephalin gene expression is decreased in a somewhat delayed and longer lasting manner. These patterns of temporal changes in biosynthesis and release of the neuropeptide presumably account for the limited changes in its steady state levels.
Brain Res Mol Brain Res 1990 Aug
PMID:Enkephalin biosynthesis and release in mouse striatum are inhibited by GABA receptor stimulation: compared changes in preproenkephalin mRNA and Tyr-Gly-Gly levels. 217 Aug

The putative structural gene mepA of the penicillin-insensitive murein endopeptidase from Escherichia coli was cloned and sequenced. N-terminal sequence determination with the isolated endopeptidase protein showed that this enzyme is coded by the mepA gene and that it is synthesized initially with an N-terminal signal peptide. No significant sequence homology with the other (penicillin-sensitive) murein endopeptidase (dacB) or any other protein was found. The precise chromosomal mapping position of mepA relative to two other genes, aroC and fabB, was shown to be 50.4 min. E. coli strains carrying multicopy plasmids with the mepA gene produced 5-6-fold more endopeptidase and secreted it into the periplasm, where it appeared to function normally in vivo since the release of cell wall peptides into the medium increased in parallel. The transformed cells were, however, not unusually sensitive to penicillin and their murein had a normal degree of cross-bridges.
Mol Microbiol 1990 Feb
PMID:Cloning and characterization of mepA, the structural gene of the penicillin-insensitive murein endopeptidase from Escherichia coli. 218 43

Leishmania mexicana, like other species of the genus, has a major 63-kDa surface glycoprotein (gp63) that is an active protease. Reports differ as to whether gp63 is a neutral or an acidic protease. Using three radiolabeled synthetic peptide substrates, gp63 purified from L. m. mexicana is most active at pH 6.5-7.5, in three different buffer systems, and appears to be a sequence-specific endopeptidase. The full extent of sequence specificity is undetermined, but these experiments suggest a strong preference for cleavage at serine or threonine residues. In common with other metalloproteases, the cleavage is on the amino side of the recognition residue.
Mol Biochem Parasitol 1990 May
PMID:Leishmania mexicana mexicana gp63 is a site-specific neutral endopeptidase. 219 21

Neuropeptide Y (NPY), a potent vasoconstrictor peptide found in sympathetic neurons, was analyzed in human inferior turbinate nasal mucosal tissue. NPY content determined by radioimmunoassay was 3.13 +/- 0.79 pmol/g tissue (n = 6) in mucosa extracted with ethanol-acetic acid. NPY-immunoreactive nerves were found around small muscular arteries, arterioles, arteriovenous anastomoses, and as free fibers near arteriolar and venous vessels. They formed a plexus around the arterial vessels, and were also present between vascular smooth muscle cells. Few NPY fibers were present near glands or the epithelium. [125I]NPY binding sites were localized by autoradiography to small muscular arteries, arterioles, and a few venous sinusoids. In explant culture experiments, 4 microM NPY did not stimulate release of [3H]glucosamine-labeled glycoconjugates or lactoferrin (a product of serous cells) from nasal mucosal fragments. Degradation of NPY by a tissue homogenate was rapid (t1/2 = 13.5 +/- 2.3 min). The degradation was inhibited by thiorphan and phosphoramidon, inhibitors of neutral endopeptidase activity. NPY released from sympathetic neurons may play a role as a constrictor of arterial vessels and regulate vasomotor tone in the human nasal mucosa.
Am J Respir Cell Mol Biol 1990 Aug
PMID:Neuropeptide Y (NPY) in human nasal mucosa. 237 51

The biologic activity of substance P has been demonstrated to be limited both in in vivo and in vitro by a membrane-bound protease, neutral endopeptidase (EC 3.4.24.11). The interaction of substance P with its receptor on guinea pig lung tissues was studied in the presence of an inhibitor of neutral endopeptidase under conditions that protect the peptide from degradation. Uptake of 0.1 nM [125I]-BH-substance P in lung membrane preparations was rapid at 4 degrees C, reaching equilibrium in 30 to 40 min, and binding was stable for at least 30 min thereafter. Binding was reversible and saturable. Scatchard analyses of saturation binding data are consistent with a single class of receptor molecules in both lung parenchymal and airway membranes, with a Kd of 2 to 3 nM and a receptor density of 4,000 to 5,000 fmol/g wet wt of tissue. In competitive binding experiments, neurokinin A and substance P methyl ester were equipotent and required approximately 100-fold higher concentrations to effect equivalent displacement than unlabeled substance P. Eledoisin also competed for [125I]-BH-substance P binding, but was less effective than the other analogs. The spasmogenically inactive derivative, substance P 1-9, did not compete for substance P binding at concentrations as high as 1 microM. Binding of [125I]-BH-substance P was rapidly and completely reversed by addition of 0.1 mM GTP, suggesting that association with a GTP binding protein is required for high affinity binding of substance P to its receptor in lung. The substance P receptor molecule was further characterized by covalently crosslinking [125I]-BH-substance P to membrane preparations followed by SDS-PAGE of the solubilized material.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1989 Oct
PMID:Characterization of the substance P receptor in guinea pig lung tissues. 248 20

This paper describes the enzyme catalyzed synthesis of the undecapeptide substance P from its non-associated fragments (1-7) and (8-11) or (1-8) and (9-11). The fragment condensation was mediated by the use of product specific antibodies as molecular traps. As catalyst a previously purified endopeptidase was used which specifically hydrolyzes substance P at the Phe7-Phe8 and Phe8-Gly9 bonds. The synthesis was performed in analytical scale and product formation was guided by reversed phase HPLC combined with radioimmunoassay. It appeared that the substance P fragments (1-8) and (9-11) were condensed to a larger extent than (1-7) and (8-11). This observation may well result from the higher affinity of the antibodies observed for substance P (8-11) as compared to that found for the other fragments. Increased concentration of the antibodies also seemed to result in enhanced resynthesis of substance P.
J Mol Recognit 1988 Apr
PMID:Substance P synthesis by enzymatic fragment condensation using product-directed antibodies as molecular traps. 248 23


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