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)

All of several hundred erythromycin resistant single site mutants of Bacillus subtilis W168 are temperature senstive for sporulation. The mutants and wild type cells grow vegetatively at essentially the same rates at both permissive (30 degrees C) and nonpermissive (47 degrees C) temperatures. In addition cellular protein synthesis, cell mass increases and cell viabilities are similar in mutant and wild type strains for several hours after the end of vegetative growth (47 degrees C). in the mutants examined, the temperature sensitive periods begin when the sporulation process is approximately 40% completed, and end when the process is 90% completed. At nonpermissive temperatures, the mutants produce serine and metal proteases at 50% of the wild type rate, accumulate serine esterase at 16% of the wild type rate, and do not demonstrate a sporulation related increase in alkaline phosphatase activity. The eryR and spots phenotypes cotransform 100%, and cotransduce 100% using phage PBS1. Revertants selected for ability to sporulate normally at 47 degrees C (spot), simultaneously regain parental sensitivity to erthromycin. No second site revertants are found. Ribosomes from eryR spots strains bind erythromycin at less than 1% of the wild type rate. A single 50S protein (L17) from mutant ribosomes shows an altered electrophoretic mobility. Ribosomes from spo+ revertants bind erythromycin like parental ribosomes and their proteins are electrophoretically identical to wild type. These data indicate that the L17 protein of the 50S ribosomal subunit from Bacillus subtilis may participate specifically in the sporulation process.
Mol Gen Genet 1977 Jan 18
PMID:Erythromycin resistant mutations in Bacillus subtilis cause temperature sensitive sporulation. 40 47

Cytotoxic T lymphocytes (CTL) contain a potent cytolytic pore-forming protein (PFP, perforin or cytolysin) localized in their cytoplasmic granules. In the presence of calcium, perforin lyses a variety of target cells (TC) non-specifically. CTL, however, are generally resistant to the lytic effect of perforin. In this work, cytoplasts from CTL and susceptible TC were made by centrifuging cells on a Ficoll density gradient in the presence of cytochalasin B. Characterization by electron microscopy and a serine esterase assay established that both CTL and TC cytoplasts were completely devoid of nuclei and CTL cytoplasts contained essentially no granules. CTL cytoplasts are just as resistant to perforin-mediated lysis as the intact CTL, and both TC and their corresponding cytoplasts are very sensitive to lysis. Furthermore, CTL cytoplasts are less effective than TC cytoplasts in inhibiting hemolysis, a property shared by the respective intact cells. These results indicate that soluble granular components do not confer resistance on CTL, and suggest that the protective agent(s) acts by impeding perforin binding to the CTL membrane.
Mol Immunol 1991 Sep
PMID:Cytoplasts from cytotoxic T lymphocytes are resistant to perforin-mediated lysis. 192 7

Treatment of monocytes or K562 cells with proteolytic enzymes like pronase or trypsin, increases both the affinity of the type II Fc receptor for IgG and the signaling via this receptor. In the present study we evaluated whether other proteases could similarly enhance Fc gamma RII affinity. We furthermore assessed whether all cell types expressing Fc gamma RII display this effect. Therefore, proteins from the coagulation system and PMN-derived enzymes were tested for effects on Fc gamma RII-mediated ligand binding. Enzymes of the coagulation system were tested both in fibrinogen-depleted plasma, as well as in purified form. No effects were found on Fc gamma RII-mediated rosette formation for both situations. In contrast, supernatant of stimulated granulocytes as well as leucocyte elastase were observed to be active in augmenting EA-hIgG rosette formation of thrombocytes and myeloid cell lines K562 and U937. The B cell lines Raji and Daudi, did not show enhanced rosette formation after enzyme treatment. The active component from granulocyte supernatant was partially characterized as a serine esterase with an apparent Mw of 30 kD. We tested whether the isotype specificity of Fc gamma RII on K562 cells changes upon enzyme treatment. It was found that all three tested murine subclasses gamma 1, gamma 2a, gamma 2b, bound equally well to this receptor, and interaction with all isotypes was enhanced to the same extent.
Mol Immunol 1990 Dec
PMID:PMN-derived proteases enhance the affinity of Fc gamma receptor II on myeloid cells, but not on B cells. 214 7

The cytotoxic serine protease B (CSP-B) gene is activated during cytotoxic T-lymphocyte maturation. In this report, we demonstrate that the PEER T-cell line (bearing gamma/delta T-cell receptors) accumulates CSP-B mRNA following exposure to 12-O-tetradecanoylphorbol-13-acetate (TPA) and N6-2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (bt2cAMP) because of transcriptional activation of the CSP-B gene. TPA and bt2cAMP act synergistically to induce CSP-B expression, since neither agent alone causes activation of CSP-B transcription or mRNA accumulation. Chromatin upstream from the CSP-B gene is resistant to DNase I digestion in untreated PEER cells, but becomes sensitive following TPA-bt2cAMP treatment. Upon activation of PEER cells, a DNase I-hypersensitive site forms upstream from the CSP-B gene within a region that is highly conserved in the mouse. Transient transfection of CSP-B promoter constructs identified two regulatory regions in the CSP-B 5'-flanking sequence, located at positions -609 to -202 and positions -202 to -80. The region from -615 to -63 is sufficient to activate a heterologous promoter in activated PEER cells, but activation is orientation specific, suggesting that this region behaves as an upstream promoter element rather than a classical enhancer. Consensus AP-1, AP-2, and cAMP response elements are found upstream from the CSP-B gene (as are several T-cell-specific consensus elements), but the roles of these elements in CSP-B gene activation have yet to be determined.
Mol Cell Biol 1990 Nov
PMID:Transcriptional activation of the human cytotoxic serine protease gene CSP-B in T lymphocytes. 223 10

We have previously shown that the developmentally regulated gene D2 is induced during aggregation by pulses of cAMP, which act via the cell surface receptor and consequent signal transduction pathways (W. Rowekamp and R.A. Firtel, 1980, Dev. Biol. 79, 409-418; S.K.O. Mann and R.A. Firtel, 1987, Mol. Cell. Biol. 7, 458-469; S.K.O. Mann, C. Pinko, and R.A. Firtel, 1988, Dev. Biol., in press). In this manuscript, we compare the complete derived amino acid sequence for D2 to two cloned and sequenced eukaryotic esterases and examine the requirement of the D2 gene product for development. Amino acid sequence data comparisons suggest that D2 encodes a serine esterase with strong sequence identity to Torpedo acetylcholine esterase and a Drosophila esterase. The protein has a putative leader sequence, suggesting that it is shunted into vesicles. Using an antisense gene construct driven by a Discoidin I promoter, whose transcriptional activity depends on the growth conditions of the cells, we show that inhibition of D2 mRNA accumulation results in an abnormal developmental program that includes the absence of normal streaming and incomplete aggregate formation and subsequent development. We suggest that D2 encodes an esterase function required for proper aggregation and subsequent development.
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PMID:Molecular analysis of a developmentally regulated gene required for Dictyostelium aggregation. 290 7

Both interleukin-1 alpha (IL-1 alpha) and IL-1 beta are initially translated as approximately Mr 30,000 polypeptides, lacking hydrophobic or signal sequence that could facilitate transmembrane translocation and release of mature IL-1 (Mr 17,500). The current study utilizes an antiserum specific for murine IL-1 alpha in order to investigate membrane associated IL-1 alpha polypeptides and possible postsynthetic modifications of the IL-1 alpha precursor, that might account for its intracellular transport. Cell surface iodination of endotoxin stimulated murine macrophages allowed the detection of IL-1 molecules in size similar to the IL-1 alpha precursor (Mr 33,000). Membrane bound IL-1 alpha was sensitive to degradation by serine esterase activity to yield IL-1 peptides of Mr 16,000 to 18,000. Endotoxin stimulated macrophages, but not unstimulated cells, incorporated 32PO4 into the IL-1 alpha precursor. The phosphate label of the IL-1 alpha precursor is resistant to hydroxylamine and alkaline phosphatase treatment. Released IL-1 is not phosphorylated. Approximately 10% of the phosphorylated IL-1 alpha precursor is membrane bound and associated with fractions enriched in lysosomal vesicles. These data are consistent with a model for mIL-1 expression, in which pro IL-1 alpha is post-synthetically modified to achieve intracellular transport and further suggest that mIL-1 may be a prerequisite for the release of IL-1.
Mol Immunol 1988 Nov
PMID:Structure and function of membrane IL-1. 326 77

C1 has been partially purified from serum and its ability to activate has been studied. The activation status of C1 was measured using a sensitive hemolytic assay which allowed the activation status of C1 in serum to be monitored. C1 did not activate in serum but would spontaneously activate when separated from certain other serum proteins, in particular, the C1-inhibitor protein. The activation of C1 was time and concn dependent, but addition of fully activated C1 did not affect either the rate or extent of activation. The activation of C1 could be inhibited reversibly by C1-inhibitor. This action of the C1-inhibitor was over and above its ability to regulate fully activated C1 by covalent bond formation with either the serine esterase of C1s or C1r. The results presented suggest that the C1-inhibitor plays a dual role in the regulation of C1 activation. The regulatory actions of C1-inhibitor would account for the presence of C1 in a zymogen form and for the episodic nature of complement consumption observed in individuals with genetic deficiencies of the C1-inhibitor protein.
Mol Immunol 1987 Jun
PMID:Regulation of the activation of C1 in serum. 365 2

The membrane attack complex of human complement and its highly purified precursor proteins have been analyzed for phospholipase activity. Using three different sensitive assays, phospholipase A1, A2, C or D activity could not be detected. Based on the sensitivity of the assays employed, these results indicate the complement-mediated membrane damage is not enhanced by covalent breakdown of membrane phospholipids, but is entirely caused by physical action of the membrane attack complex. The results also imply that the putative serine esterase sites of C6 and C7 are not acting on phospholipids.
Mol Immunol 1983 Apr
PMID:The membrane attack complex of complement and its precursor proteins lack phospholipase activity. 686 55

Granzyme B (also termed fragmentin 2) is a prototypic member of a subfamily of serine proteases expressed in the cytoplasmic granules of cytotoxic T lymphocytes and natural killer cells, and has been implicated in the destruction of targeted cells. Studies on the role of all granzymes in the cytolytic response would be greatly facilitated by the availability of specific anti-granzyme antisera. Three synthetic peptides corresponding to amino acid residues 1-17, 92-109 and 139-157 of human granzyme B were predicted to be immunogenic in the mouse, based on their hydrophilicity, accessibility to solvent, polymorphism with respect to mouse granzyme B and by comparison with X-ray crystallographic models of the rat mast cell protease II. Each peptide was conjugated to keyhole limpet hemocyanin and used to produce monoclonal antibodies in BALB/c mice. The monoclonal antibodies produced generally exhibited strong and specific reactivity with the respective immunizing peptide. However, only those antibodies detecting the peptide corresponding to residues 139-157 were able to detect native or denatured granzyme B, in direct binding studies with purified granzyme B or by immunoblotting. As an alternative approach for antiserum production, mice were immunized with whole, proteolytically active granzyme B isolated by immuno-affinity purification from NK tumour cell lysates, using one of the monoclonal antibodies generated. Despite the overall structural similarities between the various human granzymes, these mouse antisera surprisingly reacted only with granzyme B. Indeed, the reactivity of these polyclonal antisera was specifically abrogated by preincubation with the peptide corresponding to amino acid residues 139-157. This peptide stretch therefore represents an immunodominant portion of the granzyme B molecule in the mouse. Given the analogous structures of serine protease families expressed in leukocytes, these findings have implications for the production of monospecific antisera to granzymes and related proteases.
Mol Immunol 1995 Aug
PMID:The peptide loop consisting of amino acids 139-157 of human granzyme B (fragmentin 2) contains an immunodominant epitope recognized by the mouse. 756 17

Exposure of rabbit pulmonary arterial smooth muscle cells to 10 microM of the calcium ionophore A23187 dramatically stimulates cell membrane-associated phospholipase A2 activity and arachidonic acid release. In addition, A23187 also enhances cell membrane-associated serine esterase activity. Serine esterase inhibitors phenylmethylsulfonylfluoride and diisopropyl fluorophosphate prevent the increase in serine esterase and phospholipase A2 activities and arachidonic acid release caused by A23187. A23187 still stimulated serine esterase and phospholipase A2 activities and arachidonic acid release in cells pretreated with nominal Ca2+ free buffer. Treatment of the cell membrane with A23187 does not cause any appreciable change in serine esterase and phospholipase A2 activities. Pretreatment of the cells with actinomycin D or cycloheximide did not prevent the increase in the cell membrane associated serine esterase and phospholipase A2 activities, and arachidonic acid release caused by A23187. These results suggest that (i) a membrane-associated A2 activity (ii) in addition to the presence of extracellular Ca2+, release of Ca2+ from intracellular storage site(s) by A23187 also appears to play a role in stimulating the cell membrane-associated serine esterase and phospholipase A2 activities does not appear to require new RNA or protein synthesis.
Mol Cell Biochem 1994 Jan 26
PMID:Role of membrane associated serine esterase in the activation of phospholipase A2 by calcium ionophore (A23187) in pulmonary arterial smooth muscle cells. 802 91


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