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)

Conditioned media from Rous sarcoma virus transformed chicken embryo fibroblasts stimulate the uptake of 2-deoxyglucose in normal chicken fibroblasts. The factor responsible for this effect, which is also shed in very low amount by non-transformed fibroblasts, is destroyed by trypsin and not linked to the protease and plasminogen activator activities present in the media. Its apparent molecular weight, determined by gel filtration, is about 20,000 daltons. The factor released by transformed cells might be related to the monomeric form of a family of glucose binding and transport proteins recently reported by Lee and Lipmann ('78) to be detached by detergents from normal and transformed cells.
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PMID:Hexose uptake enhancing factor released from Rous sarcoma cells. 624 29

Fifteen transformation defective sensitive mutants of Rous sarcoma virus have been investigated to see if the expression of the pp60src-associated protein kinase activity correlated with other parameters of transformation such as altered growth control, morphological changes, increased hexose transport, and increased plasminogen activator protease synthesis. The expression of a protein kinase activity paralleled or preceded the onset of other parameters of transformation with but one exception: altered control of cell growth. The stability of the pp60src molecule in mutant-infected cells at the nonpermissive temperature was investigated with the finding that mutant pp60src did not show an increased turnover at the nonpermissive temperature as compared to wild type virus pp60src. Furthermore, it could be shown that pre-existing pp60src in mutant-infected cells maintained at the non-permissive temperature became activated after temperature shift to the permissive temperature. Temperature shift performed under conditions of inhibition of new protein synthesis with cycloheximide, puromycin, or emetine was followed by greatly increased protein kinase activity, and a parallel phosphorylation of pp60src itself in tyrosine residues. Morphological features of transformation could be demonstrated likewise under conditions of inhibition of protein synthesis.
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PMID:In vitro transformation with Rous sarcoma virus and the pp60src-associated protein kinase. 626 96

Chicken embryo fibroblasts (CEF) transformed by Rous sarcoma virus (RSV) exhibit increases in both a cell-associated and a secreted form of plasminogen activator (PA). The mechanism whereby the membrane-bound, cell-associated form of PA is processed to an extracellular, soluble form has been examined in cultures of chicken fibroblasts transformed by a temperature-sensitive mutant of RSV. We report that chymostatin, a protease inhibitor of limited specificity, inhibits the release of PA from tsRSVCEF while causing accumulation of cell-associated PA. Chymostatin's effect on PA release is specific, reversible and appears to be due to its anti-proteolytic capacity. Chymostatin does not inhibit cellular protein synthesis or interfere in the assay used to measure PA. A chymostatin-sensitive protease activity has been found in a membrane fraction isolated from tsRSVCEF.
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PMID:Inhibition of plasminogen activator release from transformed chicken fibroblasts by a protease inhibitor. 627 25

In order to investigate a possible correlation between in vitro transformation and tumorigenicity in ovo, a new temperature-sensitive class T mutant of Rous Sarcoma Virus was isolated with a lower (39 degrees 5C) restrictive temperature for morphological transformation. This lower restrictive temperature was compatible with the survival of chicken and duck eggs for the tumorigenicity studies. In chicken embryo fibroblasts (CEF) infected by this new mutant, PA 17, and cultured at 39 degrees 5C, increase of hexose uptake, plasminogen activator production and anchorage-independent growth were only partially restricted, requiring incubation at 41 degrees 5C for a complete shut-off. Tumorigenicity in chicken and duck eggs inoculated with CEF infected and transformed by PA 17 was restricted at 39 degrees 5C, correlating well with the restriction of morphological transformation at this temperature. The kinase activity of the transforming protein pp60src in lysates of PA 17 infected cells cultured at permissive or restrictive temperatures was labile in RIPA buffer, as in the case of some previously examined ts T mutants. In the non-ionic detergent NP40 buffer, the kinase activity of PA17 infected cell lysates was better conserved and showed a moderate temperature dependence. These results suggest that, in spite of the correlations between the transformed cell phenotype in vitro and cell tumorigenicity in ovo, it is difficult to establish a quantitative relationship.
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PMID:A ts T mutant of Schmidt Ruppin strain of Rous sarcoma virus restricted at 39.5 degrees C for the morphological transformation and the tumorigenicity of chicken embryo fibroblasts. 627 5

We have isolated and characterized mutants of Rous sarcoma virus which induce some parameters of transformation but fail to fully induce other parameters. We believe these mutants code for a pp60src which phosphorylates some targets well but phosphorylates others poorly. Using these mutants, we examined the phosphorylation of a 36,000 Mr protein which is phosphorylated on a tyrosine in cells transformed by Rous sarcoma virus, in an attempt to correlate this phosphorylation with the expression of specific transformation parameters. We found that phosphorylation of the 36,000 Mr protein was neither necessary nor sufficient for loss of fibronectin or for loss of density-dependent inhibition of growth. Phosphorylation of the protein was not sufficient for morphological alterations, increased hexose transport, or loss of adhesiveness. For the parameters measured, the best correlation was with increased plasminogen activator. In addition, it is noteworthy that cells infected with the mutant CU2 displayed low levels of phosphorylation of the 36,000 Mr protein and also were deficient in anchorage-independent growth and tumorigenicity, raising the possibility that the phosphorylation of the 35,000 Mr protein may be required for malignant growth properties.
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PMID:Phosphorylation of a 36,000 Mr cellular protein in cells infected with partial transformation mutants of rous sarcoma virus. 628 26

We have tested the effect of the culture medium of chicken embryo fibroblasts (CEF) transformed by Rous sarcoma virus (RSV) on plasminogen activator (PA) activity of normal and RSV-infected cells. The results obtained showed that fibrin digestion by cultures of normal uninfected and RSV-infected cells directly attached to a fibrin substrate was increased when the cells were exposed to the supernatant of an 18 h-culture of CEF transformed by RSV. Addition of cycloheximide to the supernatant completely abolished this effect. Similarly, exposure of both normal and RSV-infected cells to the culture medium of RSV-transformed CEF resulted in a marked increase of the soluble PA activity present in the supernatant. This effect, however, was not abolished by inhibition of protein synthesis. For both the cell-bound and soluble PA activities of normal and RSV-infected cells the stimulatory effect was transient, being maximal between 8 and 12 h of exposure to the transformed cell-conditioned medium and disappearing after 24 h. A possible correlation with transformation-enhancing factor(s), previously reported to be present in the culture medium of transformed cells, is discussed.
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PMID:Enhancement of plasminogen activator activity by the culture medium of Rous sarcoma virus-transformed cells. 629 83

A chymostatin-sensitive step in the release of plasminogen activator from transformed fibroblasts has been described recently. By using synthetic peptidyl substrates, we have detected and characterized a chymostatin-sensitive peptidase activity in chicken embryo fibroblasts transformed by Rous sarcoma virus. The activity represents a neutral endopeptidase that exhibits phenylalanine specificity and is inhibited by diisopropyl fluorophosphate. A detailed inhibitor profile of the enzyme activity shows that it is distinct from other chymotrypsin-like phenylalanine-preferring peptidases. The endopeptidase activity in transformed fibroblasts is increased over that of parallel cultures of normal fibroblasts. The mechanism of enzyme inhibition by chymostatin is indicated by these studies, and the possible role of the enzyme in modulating plasminogen activator secretion is discussed.
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PMID:Detection and partial characterization of a chymostatin-sensitive endopeptidase in transformed fibroblasts. 630 Aug 32

We have synthesized peptidyl prodrugs of doxorubicin (Dox) designed to be selective substrates of plasmin. Such prodrugs might be locally activated by the elevated levels of plasmin produced near many solid tumors under the action of tumor-associated plasminogen activators. One such prodrug, 3'-(D-Val-Leu-Lys)-Dox, was obtained via a mixed-anhydride coupling with isobutyl chloroformate between the protected peptide Fmoc-D-Val-Leu-N epsilon-Fmoc-Lys-OH and doxorubicin, followed by removal of the Fmoc groups with anhydrous ammonia. Compared to doxorubicin, the prodrug showed about a 7-fold improved selective cytotoxicity against chicken embryo fibroblasts transformed with the Rous sarcoma virus (which produce high levels of plasminogen activator) compared to normal cells (which produce low levels of plasminogen activator). However, the prodrug was a very poor plasmin substrate, and although in vivo tests against the murine B16 melanoma showed that the prodrug was active, the maximum T/C obtained was less than that achieved by doxorubicin even at 25 times the molar concentration of prodrug. Qualitatively similar results were obtained for a far more hydrophobic prodrug, 3'-(Boc-Val-Leu-Lys)-Dox. These results demonstrate that peptidyl prodrugs of doxorubicin designed as plasmin substrates are more selective anticancer agents in vitro than doxorubicin itself but that the bulky anthracycline moiety probably prevents efficient plasmin-catalyzed conversion to the active parent drug, so that, in their present form, these drugs are not potent enough to allow a determination as to whether or not they are more selective in vivo.
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PMID:Plasmin-activated prodrugs for cancer chemotherapy. 2. Synthesis and biological activity of peptidyl derivatives of doxorubicin. 630 53

Epithelial-like chondrocytes obtained from chick embryo were transformed with Rous sarcoma virus. Cellular transformation was monitored looking at the morphology change, the cell growth, and the expression of plasminogen activator. Analysis on polyacrylamide gel of intracellular and secreted proteins showed: 1) a disappearance of the specific products of differentiated chondrocytes; 2) a switch in the collagen synthesis from the type II, the chondrocyte-specific type, to the type I, characteristic of fibroblasts and other cells of mesenchymal origin; 3) an enhancement of fibronectin synthesis. Analysis of the proteins from chondrocytes infected with Rous-associated virus 1, a virus unable to induce cell transformation in vitro, indicated that the altered expression of the differentiated proteins in Rous sarcoma virus-infected chondrocytes depended upon the action of src gene product.
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PMID:The culture of chick embryo chondrocytes and the control of their differentiated functions in vitro. Transformation by rous sarcoma virus induces a switch in the collagen type synthesis and enhances fibronectin expression. 630 82

Expression of the src gene of Rous sarcoma virus in chicken embryo neuroretinal cells results in morphological transformation and sustained proliferation of this normally resting cell population. PA101 and PA104 are two mutants of Rous sarcoma virus which induce neuroretinal cell proliferation in the absence of morphological transformation. Their mitogenic property is temperature sensitive, and they both encode p60src proteins with low kinase activity. To study the role of the mitogenic function and protein kinase activity of p60src in tumorigenesis, we investigated the oncogenicity of PA101 and PA104. Both mutants were less tumorigenic than wild-type virus when injected into chicks. Tumorigenicity was further assayed by inoculating infected chicken embryo fibroblasts and neuroretinal cells onto the chorioallantoid membrane of embryonated duck eggs. This system provides a nonpermissive and immunodeficient environment for xenogenic cell grafting and allows the study of cell tumorigenicity within a temperature range of 37 to 39.5 degrees C. Chicken embryo fibroblasts and neuroretinal cells infected with PA101 were as tumorigenic as wild type-infected cells at 37 degrees C, but tumor development was significantly reduced at 39.5 degrees C. In contrast, both cell types infected with PA104 displayed sharply reduced tumorigenicity. Cell cultures derived from PA101 tumors induced on the chorioallantoid membrane were similar to the corresponding cells maintained in vitro in terms of morphology, production of plasminogen activator, relative amounts of phosphotyrosine in total cellular proteins, and phosphorylation of 34,000-molecular-weight protein. These results indicate that the expression of the mitogenic function of src does not account per se for cell tumorigenicity and that tumor formation is compatible with low levels of p60src protein kinase activity.
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PMID:Role of the mitogenic property and kinase activity of p60src in tumor formation by Rous sarcoma virus. 631 32


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