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)

The secretion of elevated levels of proteinases is considered to be a distinct property of most transformed cells. The cellular and secreted levels of plasminogen activators and collagenases have been examined in the nonmalignant human osteosarcoma (HOS), the malignant Kirsten murine sarcoma virus transformed (KHOS/NP), the temperature sensitive revertant of virus transformed HOS (KHOS-240S) and N-methyl-N'-nitro-N-nitrosoguanidine transformed HOS (MNNG/HOS) clones. Virus and MNNG transformed clones exhibit 100- and 7-fold higher cellular and and 270- and 30-fold higher extracellular plasminogen activator (PA) activity as compared with untransformed HOS controls. The cellular PA activity of the revertant clone is similar to but the secreted level is slightly higher than the HOS controls. SDS-PAGE in the presence of casein and plasminogen is consistent with the major PA species of urinary type (u-PA) and with the absence of PA inhibitor in the parent and revertant clones. The cellular levels of active collagenase are low in all the clones. However, on activation by trypsin, the two active collagenase bands of similar intensity are observed for all the lines in SDS-PAGE in the presence of gelatin. While there appears to be some elevation of secreted collagenase prior to trypsin activation, the activated collagenases appear to have the same size and activity in all of the clones.
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PMID:Synthesis and secretion of plasminogen activators and collagenases in human cells transformed by Kirsten murine sarcoma virus and N-methyl-N'-nitro-N-nitrosoguanidine. 256 62

The plasminogen activator (PA) in clonal osteogenic sarcoma cells of rat origin (UMR 106-01 and UMR 106-06) and in osteoblast-rich rat calvarial cells has been characterized using specific antibodies to be tissue-type PA (tPA). An Mr value of 75,000 by SDS-polyacrylamide gel electrophoresis and fibrin autoradiography supports this characterization. There was also evidence for an Mr 105,000 component, which could be due to a proteinase-inhibitor complex. The mechanism of regulation of this tPA activity has been studied in the clonal osteogenic sarcoma cells. Parathyroid hormone (PTH) and prostaglandin E2, which increase cyclic AMP production in the sarcoma cells, also increased tPA activity. The sensitivity and magnitude of the tPA response to PTH and prostaglandin E2 were increased by simultaneous treatment with isobutylmethylxanthine (IBMX) at drug concentrations which had little effect themselves on tPA activity. In UMR 106-06 cells, which unlike UMR 106-01 cells show a cyclic AMP response to calcitonin, tPA activity was also increased in response to calcitonin, and the effect was enhanced by IBMX. 1,25-Dihydroxyvitamin D-3 also increased tPA activity in the cells, but this response was not modified by IBMX. Synthetic peptide antagonists of PTH-responsive adenylate cyclase, [34Tyr]-hPTH (3-34) amide and [34Tyr]-hPTH (5-34) amide, inhibited the PTH-induced increase in tPA activity over the same concentration range at which they inhibited cyclic AMP production, but the antagonist peptides had no effect on the tPA responses to prostaglandin E2, calcitonin or 1,25-dihydroxyvitamin D-3. These data indicate that cyclic AMP mediates the actions of PTH, prostaglandin E2 and calcitonin in increasing tPA activity in the clonal osteogenic sarcoma cells. 1,25-Dihydroxyvitamin D-3, on the other hand, increases tPA activity through a mechanism independent of cyclic AMP.
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PMID:Cyclic AMP-dependent and -independent effects on tissue-type plasminogen activator activity in osteogenic sarcoma cells; evidence from phosphodiesterase inhibition and parathyroid hormone antagonists. 301 47

Low-molecular-weight protein factors (Mr 8,000 to 18,000) from serum-free conditioned medium of human fibrosarcoma (8387) cells reversibly enhanced the secretion of proteinase-inhibitory activity by cultured normal human skin fibroblasts. This inhibitory activity could be absorbed by immobilized plasminogen activator (PA) of urokinase type but not by heparin, and it was sensitive to treatment with sodium dodecyl sulfate. The secretion of a heparin-binding Mr 60,000 proteinase inhibitor, resembling protease nexin, was also detected. Early passages of adult skin fibroblasts do not contain or secrete PA. When cell types secreting this enzyme were tested, the fibrosarcoma-derived factors decreased the PA secretion detectable after sodium dodecyl sulfate treatment in all conditioned media of normal and malignant fibroblastic cells examined, including the 8387 cell line itself. However, no effects on the secretion of PA by normal or malignant cells of epithelioid origin or by melanoma cells were seen. A similar preparation from human epidermoid carcinoma (A431)-conditioned medium did not affect the PA activity or secretion of proteinase inhibitors from fibroblastic cells. The ability of sarcoma cells to modulate the production of PA inhibitors is a novel characteristic in the regulation of cellular proteolysis.
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PMID:Regulation of plasminogen activator activity in human fibroblastic cells by fibrosarcoma cell-derived factors. 392 Dec 41

Plasma membranes were purified from rat liver, muscle and sarcoma tissues and from human liver and hepatoma tissues. The plasma membranes all contained DFP-sensitive, neutral proteolytic activity. Plasma membranes from all normal tissues contained a single DFP-binding protein of apparent molecular weight 68,000. Only the plasma membranes from tumour tissue contained a plasminogen activator; the DFP-binding proteins from these membranes were more diverse than those from the normal samples. The rat liver plasma membrane proteinase was purified. It was a labile enzyme sensitive to inhibition by DFP and by calcium ions, and with a broad substrate specificity. A similar protein was the sole DFP-binding protein in rat liver microsomes. This and the properties of the enzyme suggested a possible role in the processing and secretion of newly-synthesized protein.
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PMID:Membrane proteinases from normal and neoplastic tissues in man and the rat. 609 93

Vimentin-positive, desmin-negative cells were established in culture from the nodule and from apparently normal palmar aponeurosis of a patient with Dupuytren's disease and compared with normal human embryonic and adult fibroblasts or sarcomatous cells. Cells from the nodule display in vitro biological properties that are intermediate between those expressed by normal fibroblasts and sarcoma cells or cells from the nodule transformed with SV40 virus. Thus, they represent an interesting in vitro model of partially transformed human cells. This behavior is not evolutive and justifies the classification of Dupuytren's disease among the benign mesenchymal tumors. The production of high level of plasminogen activator probably explains the local reactive pathology, and could act as a mitogenic stimulus for the proliferation of the nodule itself. Cultures derived from the apparently normal palmar aponeurosis show some but not all the abnormal growth properties of cells from nodules; this may help to explain the onset of local recurrences. Our results suggest that Dupuytren's disease is not strictly local and limited to the nodules, but affects, at least partially, the whole aponeurosis. Dupuytren's nodules could be considered as a model of tumor progression in a benign situation.
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PMID:Abnormal behavior of cultured fibroblasts from nodule and nonaffected aponeurosis of Dupuytren's disease. 619 20

On the basis of cellular morphology, a subline of mouse sarcoma virus-infected 3T3 cells was selected which released a 48 000-dalton plasminogen activator at an approx. 40-fold higher rate than those of the parent line, and which continued to do so for several months when the cells were maintained in serum-free culture medium. Culture medium (3.5 l) containing 0.6 mg plasminogen activator per l was used to purify 620 micrograms of the enzyme 130-fold with a yield of 32% by affinity chromatography followed by anion exchange chromatography and gel filtration. Crucial for the yield was the use of a non-ionic detergent and of inhibitors of proteolysis to prevent adsorption and degradation, respectively. The purified enzyme was homogeneous as evaluated by SDS-polyacrylamide gel electrophoresis and had an isoelectric point of pH 9.2. The purified enzyme showed characteristics of a trypsin-like serine protease (labeling with [3H]diisopropylphosphorofluoridate which was prevented by p-nitrophenyl-p'-guanidinobenzoate) and converted the single chain of human plasminogen into two chains of plasmin with electrophoretic mobilities identical to those of the chains formed by non-purified enzyme and by human urokinase. In the absence of inhibitors, solutions of purified enzyme were stable for 24 h at 4 degrees C at pH 3-9.
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PMID:Purification and characterization of a plasminogen activator from mouse cells transformed by an oncogenic virus. 625 3

Two temperature-sensitive mutants of Fujinami sarcoma virus were isolated and characterized. Cells infected with the mutants were temperature sensitive in focus formation, colony formation, increased sugar uptake, and synthesis of plasminogen activator. The changes between transformed and nontransformed states of cultures were completely reversible by shifting the temperature. A Fujinami sarcoma virus-specific protein of 130,000 daltons, p130, was synthesized in mutant-infected cells regardless of the temperature, but the immunoprecipitates of p130 from extracts of infected cells were active in protein kinase only when cells had been incubated at the permissive temperature. These results appear to indicate that p130 is the transforming protein of Fujinami sarcoma virus, and that its protein kinase activity plays a crucial role in cell transformation by this virus.
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PMID:Mutants of Fujinami sarcoma virus which are temperature sensitive for cellular transformation and protein kinase activity. 626 8

Reports from several laboratories have suggested that the virus transformed state may be maintained either by ectopically produced growth factors or alternatively by ectopically produced serine proteases including plasminogen activator. Here we show that the maintenance of transformation induced by Kirsten sarcoma virus induced growth factor(s) is independent of serine proteases in that 1) the factors are not themselves serine proteases, and 2) the growth factors do not induce the expression of detectable serine proteases or plasminogen activator.
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PMID:Morphological transformation of cells induced by Kirsten sarcoma virus transforming factor is independent of serine proteases. 627 79

We have previously reported the purification of a plasminogen-activating serine protease with an approximate Mr of 48 000 from sarcoma-virus-transformed murine cells. We now report that under serum-free conditions the enzyme is released from the cells in an inactive form. After affinity chromatography with 4-aminobenzamidine-cellulose, ion-exchange chromatography and gel filtration, the proenzyme could be obtained from culture fluid as a pure, homogeneous protein as evaluated by polyacrylamide gel electrophoresis with sodium dodecylsulphate. Proenzyme was quantitatively converted to active enzyme by incubation with catalytic amounts of plasmin. Analysis by polyacrylamide gel electrophoresis with sodium dodecylsulphate under reducing and non-reducing conditions showed that the inactive form consisted of a single polypeptide chain with an Mr of approximately 48 000, while the active form consisted of two chains with Mr values of approximately 18 000 and 29 000 , held together by one or more disulphide bridges. The active-site reagent diisopropylfluorophosphate in radiolabelled form was incorporated into the 29 000-Mr chain of the active enzyme, but not into the inactive form. These findings provide conclusive evidence for the existence of an inactive proenzyme to this plasminogen activator and thus demonstrate and additional step in a cascade-like reaction leading to extracellular proteolysis. Regulatory as well as methodological implications of this findings are discussed.
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PMID:Plasminogen activator released as inactive proenzyme from murine cells transformed by sarcoma virus. 628 7

Several angiogenic preparations that have been shown to stimulate plasminogen activator (PA) and collagenase production by cultured bovine capillary endothelial (BCE) cells were tested for their ability to stimulate BCE cell motility in the phagokinetic track assay. Bovine retinal extract, medium conditioned by 3T3-F442A differentiated mouse adipocytes, SK HEP-1 human hepatoma cell lysate, mouse sarcoma 180 cell lysate, and medium conditioned by mouse sarcoma 180 cells stimulated motility 68.7%, 48.5%, 140.9%, 56.5%, and 102.1%, respectively, relative to untreated cells. The motility-stimulating activity of these preparations was dose dependent and linear over the 16-h assay period. Several hormones and growth factors were tested for BCE cell motility-stimulating activity, including insulin, vasopressin, fibroblast growth factor, and a partially purified preparation of sarcoma growth factor, and were found to be ineffective. 12-0-tetradecanoyl-phorbol-acetate (TPA), a potent stimulator of both PA and collagenase activities in BCE cells, also did not stimulate motility, indicating that protease production is not sufficient to stimulate BCE cell motility in this assay. Neither SK HEP-1 hepatoma cell lysate nor TPA was effective in stimulating motility in bovine aortic endothelial (BAE) cells. The inability of SK HEP-1 hepatoma cell lysate to stimulate movement in BAE cells is consistent with the observation that angiogenesis occurs by sprouting of capillaries, not large vessels.
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PMID:Stimulation of motility in cultured bovine capillary endothelial cells by angiogenic preparations. 632 76


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