Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A high molecular weight fraction of human serum (Fr-1) was found to both inhibit macrophage tumoricidal activity and enhance plasminogen activator activity in supernates over activated macrophages in vitro. Conversely, a 40- to 90-kilodalton serine esterase (Fr-3) also found in normal human serum and endotoxin enhanced tumoricidal potential and suppressed the supernatant plasminogen activator activity. Inactivation of either Fr-1 or Fr-3 by 2-mercaptoethanol or diisopropyl fluorophosphate, respectively, abolished both biologic effects. Examination of cell-associated and culture medium plasminogen activator activity before and after acidification to inactivate proteinase inhibitors indicated that suppression of plasminogen activator activity by Fr-3 or endotoxin most likely represents modulation of macrophage plasminogen activator secretion. The findings demonstrate that activated macrophages are capable of highly coordinated biologic responses to alterations in their microenvironment and suggest that it is in fact the high potential for such responsiveness that reliably characterizes the activated macrophage. The results also suggest that an endogenous regulatory system dependent on the interaction of serine esterases may operate to regulate the functional capabilities of activated macrophages.
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PMID:Modulation of plasminogen activator secretion by activated macrophages: influence of serum factors and correlation with tumoricidal potential. 29 Oct 48

We describe the characterization and purification of a trypsin-like serine protease isolated from cloned long-term culture cytolytic T cell line (CTLL AK). High amounts of proteolytic activity were isolated from extracts of CTLL AK after either nitrogen cavitation or detergent lysis. Trypsin-like protease was detected by using either the ester compound N alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester or a panel of low molecular amide substrates. The latter compounds were preferentially cleaved at the carboxyl termini of lysine and arginine residues. The enzyme activity was completely inhibited by two serine esterase inhibitors, diisopropylfluorophosphate and phenylmethanesulfonyl fluoride, and by aprotinin and meta-aminobenzamidine, which are known to block trypsin-like proteases. The pH optimum for CTLL AK-derived protease activity is 8 to 9. Analysis of the enzyme by gel filtration revealed that the cell-bound proteolytic activity was associated with a complex that could not be dissociated by treatment with Triton X-100. The CTLL AK-derived protease activity was found to reside in two proteins with relative molecular masses (Mr) of 32,000 and 40,000 daltons as determined by affinity labeling with [3H]diisopropylfluorophosphate and sodium dodecyl sulfate gel electrophoresis. High levels of enzyme activity were found in a panel of H-Y-specific cloned T cell lines with either cytolytic/suppressor (CTLL) or helper potential (THL), indicating a lack of correlation between trypsin-like protease activity and a particular T cell function. High enzyme activity was also detected in tumorigenic variants of CTLL. Furthermore, it was excluded that the trypsin-like activity detected was attributable to plasminogen activator activity. In contrast to cloned T effector cells and their in vitro or in vivo derived variants, considerably less activity was found in normal nonactivated or activated lymphocyte populations. The possible role of the trypsin-like serine protease in the function of T effector cells is discussed.
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PMID:Characterization and isolation of a trypsin-like serine protease from a long-term culture cytolytic T cell line and its expression by functionally distinct T cells. 242 97

A human cell line (RC-K8) that produces plasminogen activator was established from the peritoneal effusion of a patient with histiocytic lymphoma. The RC-K8 cell line grew mainly in single cell suspension and consisted of primitive cells with pleomorphic morphology. RC-K8 cells were positive for alpha-naphthyl butyrate esterase, acid phosphatase and periodic acid-Schiff stainings. Immunologic and molecular biological studies showed that RC-K8 cells reacted with monoclonal antibodies to B cell antigens (B1 and Leu12) and Ia antigen (OKIa1) and possessed immunoglobulin gene rearrangement in the absence of surface and cytoplasmic immunoglobulin. Neither Epstein-Barr virus nuclear antigen nor terminal deoxynucleotidyl transferase was detected in the cells. Chromosome analysis of RC-K8 disclosed 46 XY with complex abnormalities including t(11;14)(q23;q32). Intraperitoneal inoculation of RC-K8 cells to immunosuppressed newborn hamsters produced massive metastatic tumors in the lungs. The RC-K8 cell line will be of considerable value for the study of lymphomagenesis associated with t(11;14) and pulmonary metastasis of lymphoma cells.
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PMID:Characterization of a new human lymphoma cell line (RC-K8) with t(11;14) chromosome abnormality. 374 63

The purification and properties of an estradiol-sensitive hydrolytic activity from mouse uterus which fits several criteria for being an induced protein are described. The activity in the uteri of immature animals can be stimulated 2--4-fold by estradiol to that approaching the adult level. Stimulation is blocked by puromycin. The enzyme which we have designated hydrolase II, was purified approx. 400-fold to apparent homogeneity by chromatography on Affigel Blue, DEAE-cellulose and octyl-Sepharose. Hydrolase II is a single chain polypeptide with an estimated mol. wt = 65,000 daltons and has an N-terminal serine residue. A variety of N-blocked L-amino acid nitrophenyl esters are cleaved by the enzyme. Km's at pH 7.2 were all approx. 40 microns. Of substrates tested, phenylalanine nitrophenyl ester had the highest Vmax. Cbz-beta-alanine nitrophenyl ester, which is not a normal protease substrate was cleaved with a Km of 145 microM. The enzyme had no detectable activity against peptide nitroanilide substrates for trypsin-, chymotrypsin- or elastase-like enzymes. It is inhibited by ZPCK and DIFP but not by TLCK and Ala-Ala-Pro-Ala chloromethyl ketone, a potent inhibitor of elastase-like enzymes. Mouse plasma protein protease inhibitors were without effect as was SBTI. Our results rule out hydrolase II being a carnosinase, non-serine esterase, plasminogen activator, collagenase or collagenase activator and suggest that it is a chymotrypsin-like protease.
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PMID:Properties of an estrogen-induced hydrolytic enzyme from mouse uterus. 635 Jul 23

Rat urinary esterase A, a plasminogen activator with kininogenase activity, was recently purified and characterized (J. Chao (1983) J. Biol. Chem. 258, 4434-4439). A sensitive radioimmunoassay for esterase A has been developed. This assay uses a rabbit antiserum in a final dilution of 1:160 000 and the purified enzyme was labelled with 125I using a lactoperoxidase method. It detects 80 pg of immunoreactive material per tube. This antiserum has some cross-reactivity with rat urinary kallikrein (approximately 5%) but a previously characterized tissue kallikrein antiserum has negligible cross-reactivity with the urinary esterase A in the assays. Therefore, kallikrein levels are measured simultaneously in all samples to obtain accurate levels of immunoreactive esterase A. Dilutions of urine or tissue homogenates showed complete parallelism with esterase A standard curves. No cross-reactivity with dog, human or monkey urine was seen. The recovery of esterase A from rat urine was 99.7 +/- 3.5%. Intra- and between-assay errors were 6.5 and 11.2%, respectively. Immunoreactive esterase A was measured and compared with kallikrein levels in rat urine, kidney, pancreas, submandibular gland, descending colon and ileum. The urinary esterase A excretion rate was reduced significantly in rats on a high sodium, compared with a low sodium diet, but not significantly increased above control by the latter. Nonetheless, a significant correlation between urinary kallikrein and esterase A excretion rate was present. This radioimmunoassay can now be used to measure esterase A levels in urine and tissue as questions have arisen about its regulation and functional significance.
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PMID:Measurement of the rat urinary plasminogen activator (esterase A) by direct radioimmunoassay in urine and tissue. 656 99

Activated Factor B (Bb), the central serine esterase of the alternative pathway of complement activation, exhibits restricted substrate specificity in the complement system for C3 and C5. The results presented here indicate that Bb can cleave and activate plasminogen in an experimental system containing purified plasminogen and Bb; complement cellular intermediate bearing the Bb-enzyme; or cobra venom factor-stabilized Bb-enzyme (CVF,Bb). Cleavage of plasminogen by Factor Bb generated 2 disulfide-linked polypeptides with apparent m.w. of 64,000 and 25,000 to 32,000 (SDS-PAGE). Complement cellular intermediates containing the C3b, Bb-enzyme cleave 40 to 80% of 4.5 micrograms of 125I-labeled plasminogen during 30 min of incubation at 37 degrees C; native Factor B was inactive; and anti-Factor Blg inhibited by 100% the plasminogen cleavage mediated by complement cellular intermediates bearing the Bb-enzyme. Fibrinolytic activity was detected in plasminogen activator (PA) assays when purified plasminogen and 125I-labeled fibrin tubes were incubated with Bb, CVF, Bb, or complement cellular intermediates bearing the C3b,Bb-enzyme: 10 micrograms Bb released 40 to 65% of the 125I-fibrin released by 5 micrograms urokinase in 4 hr at 37 degrees C. Plasminogen activator activity of the C3b,Bb-enzyme was found to be regulated in serum. At dilutions of NHS 1:50, the PA-activity of 1.6 micrograms Bb was 100% inhibited, and at a 1:250 dilution, 50% inhibition was observed. This report describes a novel activity for the Bb-enzyme, which constitutes the C3/C5-convertase of the alternative pathway of complement activation.
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PMID:Activated factor B (Bb) of the alternative pathway of complement activation cleaves and activates plasminogen. 691 Nov 48

Phospholipase A(2) (PLA(2)) was purified to homogeneity from the supernatant fraction of rat testis homogenate. The purified 63-kDa enzyme did not require Ca(2+) ions for activity and exhibited both phosphatidic acid-preferring PLA(2) and monoacylglycerol lipase activities with a modest specificity toward unsaturated acyl chains. Anionic detergents enhanced these activities. Serine-modifying irreversible inhibitors, (p-amidinophenyl) methanesulfonyl fluoride and methylarachidonyl fluorophosphonate, inhibited both activities to a similar extent, indicating a single active site is involved in PLA(2) and lipase activities. The sequence of NH(2)-terminal 12 amino acids of purified enzyme was identical to that of a carboxylesterase from rat liver. The optimal pH for PLA(2) activity (around 5.5) differed from that for lipase activity (around 8.0). At pH 5.5 the enzyme also hydrolyzed bis(monoacylglycerol) phosphate, or lysobisphosphatidic acid (LBPA), that has been hitherto known as a secretory PLA(2)-resistant phospholipid and a late endosome marker. LBPA-enriched fractions were prepared from liver lysosome fractions of chloroquine-treated rats, treated with excess of pancreatic PLA(2), and then used for assaying LBPA-hydrolyzing activity. LBPA and the reaction products were identified by microbore normal phase high performance liquid chromatography/electrospray ionization ion-trap mass spectrometry. These enzymatic properties suggest that the enzyme can metabolize phosphatidic and lysobisphosphatidic acids in cellular acidic compartments.
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PMID:Purification and properties of a phospholipase A2/lipase preferring phosphatidic acid, bis(monoacylglycerol) phosphate, and monoacylglycerol from rat testis. 1222 68

Arabidopsis thaliana ecotype Pi-0 is resistant to Pseudomonas syringae pathovar tomato (Pst) strain DC3000 expressing the T3S effector protein AvrBsT. Resistance is due to a loss of function mutation (sober1-1) in a conserved alpha/beta hydrolase, SOBER1 (Suppressor of AvrBsT Elicited Resistance1). Members of this superfamily possess phospholipase and carboxylesterase activity with diverse substrate specificity. The nature of SOBER1 enzymatic activity and substrate specificity was not known. SOBER1-dependent suppression of the hypersensitive response (HR) in Pi-0 suggested that it might hydrolyze a plant lipid or precursor required for HR induction. Here, we show that Pi-0 leaves infected with Pst DC3000 expressing AvrBsT accumulated higher levels of phosphatidic acid (PA) compared to leaves infected with Pst DC3000. Phospholipase D (PLD) activity was required for high PA levels and AvrBsT-dependent HR in Pi-0. Overexpression of SOBER1 in Pi-0 reduced PA levels and inhibited HR. These data implicated PA, phosphatidylcholine (PC) and lysophosphatidylcholine (LysoPC) as potential SOBER1 substrates. Recombinant His(6)-SOBER1 hydrolyzed PC but not PA or LysoPC in vitro indicating that the enzyme has phospholipase A(2) (PLA(2)) activity. Chemical inhibition of PLA(2) activity in leaves expressing SOBER1 resulted in HR in response to Pst DC3000 AvrBsT. These data are consistent with the model that SOBER1 PLA(2) activity suppresses PLD-dependent production of PA in response to AvrBsT elicitation. This work highlights an important role for SOBER1 in the regulation of PA levels generated in plants in response to biotic stress.
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PMID:SOBER1 phospholipase activity suppresses phosphatidic acid accumulation and plant immunity in response to bacterial effector AvrBsT. 1991 71