Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between plasminogen activator (PA)/plasminogen activator inhibitor (PAI) activity and morphological differentiation was investigated in human neuroblastoma (NB) cells treated with retinoic acid (RA). Conditioned medium from nine NB cell lines and one closely related neuroepithelioma line was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and zymography. All NB cell lines were shown to secrete urokinase (UK)-type PA (mol. wt., 52 kDa), and all except two produced tissue PA (mol. wt., 65 kDa). Identification of the PAs was made based on molecular weight and sensitivity to inhibition by anti-UK and anti-tPA antibodies. Several cell lines expressed PA inhibitory molecules; two molecular-weight forms were observed (35 and 40 kDa) in different cell lines. Complex formation with [125]I-labelled proteases revealed specific binding with UK and trypsin but not thrombin, plasmin, or kallikrein. After treatment for 6 days with 1 microM RA, six of the cell lines exhibited an increase in cell-associated and/or secreted tPA activity, corresponding to morphological differentiation of the cells as manifested by extensive neurite outgrowth. A decrease in UK and UK-complex secretion was observed in several of these cell lines. Three cell lines exhibiting no detectable morphological alterations with RA treatment also showed no dramatic changes in PA/PAI activity. These results suggest that morphological differentiation of NB cells may be associated with alterations in the regulation of PA activity.
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PMID:Effect of retinoic acid on human neuroblastoma: correlation between morphological differentiation and changes in plasminogen activator and inhibitor activity. 259 Sep 98

Blood coagulation factor Xa (FXa) has recently been shown to function as a plasminogen receptor in the presence of procoagulant phospholipid (phosphatidylserine; PS) and Ca2+. In the current work, the possible effect of autoproteolytic and plasmin-mediated cleavage of FXa on complex formation with plasminogen was investigated. 125I-plasminogen binding to derivatives of FXa electrotransferred to polyvinylidene difluoride revealed that the autoproteolytic conversion of FXaalpha to FXabeta was required for the expression of a plasminogen binding site. In the presence of PS and Ca2+, plasmin was shown to convert FXaalpha to a FXabeta-like species at least 3 orders of magnitude faster than the autoproteolytic mechanism. This also resulted in the exposure of a plasminogen binding site. Further processing by plasmin generated a fragment (33 kDa) due to cleavage at Gly331 in the FXa heavy chain. Production of this species enhanced apparent plasminogen binding compared with FXabeta and resulted in the loss of FXa amidolytic and clotting activity. In the absence of either PS or Ca2+, the plasmin-mediated fragmentation of FXaalpha was altered to include a FXabeta-like molecule and a species (40 kDa) with intact beta-heavy chain disulfide linked to a COOH-terminal fragment of the light chain starting at Tyr44. Neither of these products was observed to interact with plasminogen. The 40-kDa species had amidolytic activity comparable with FXaalpha but inhibited clotting activity. Cumulatively the data provide the first evidence for a functional difference between the FXa subforms and suggest a mechanism where autoproteolysis and plasmin-mediated cleavage modulate the function of FXaalpha from a procoagulant enzyme to a profibrinolytic plasminogen receptor.
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PMID:Autoproteolysis or plasmin-mediated cleavage of factor Xaalpha exposes a plasminogen binding site and inhibits coagulation. 866 21

Urinary trypsin inhibitor (UTI; Mr 40 kDa) is a Kunitz-type protease inhibitor that efficiently inhibits cell-associated trypsin and plasmin activities. The aim of this study is to examine the expression pattern of UTI in the human ovarian carcinoma ascites fluid by Western blotting, zymography, immunoprecipitation, immunohistochemistry, biochemical and gene analyses and animal experiments. We have identified and characterized the 40 kDa immunoreactive UTI (UTI(40)) and 8 kDa degradation fragment (UTI(8)) in ascites fluid. The levels of UTI(40) and UTI(8) are elevated in ascites fluid taken from patients with ovarian carcinoma relative to paired plasma samples. The UTI(40) and UTI(8) were identified immunologically by the reactivity with 2 different anti-UTI antibodies recognizing different epitopes of the UTI molecule, functionally by its ability to bind trypsin and structurally by its apparent molecular mass with and without deglycosylation treatment. The purified polypeptides have been sequenced and were identical with sequences obtained from UTI and the carboxyl-terminal domain of UTI, respectively. However, UTI mRNA was not detected in the ovarian carcinoma tissue and ovarian carcinoma cell lines examined. Based on extravasation experiments using intravenously injected biotinylated inter-alpha-trypsin inhibitor (IalphaI; a precursor of UTI), we conclude that UTI(40) and UTI(8) found in the ascites fluid may result from (i) the extravasation of plasma proteins such as IalphaI into the peritoneal cavity via hyperpermeable vessels and (ii) the subsequent degradation of IalphaI and UTI(40) by tumor cell-associated trypsin-like enzymes.
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PMID:Identification and characterization of a Kunitz-type protease inhibitor in ascites fluid from patients with ovarian carcinoma. 1086 51

This study was conducted to further explore the mechanism of transforming growth factor beta1 (TGF-beta1) activation, which plays a critical role in many physiological and pathological conditions. We have previously shown that the large (270 kDa), but not small (40 kDa), mannose 6-phosphate receptors facilitate the cellular response to latent TGF-beta1 released from genetically modified cells. In this study, we explored the role of cell membrane associated transglutaminase and plasmin in mannose 6-phosphate receptor induced latent TGF-beta activation using MS and MS-9 cells bearing either no receptors or the 270 kDa mannose 6-phosphate/insulin-like growth factor II receptors, respectively. As a source of latent TGF-beta1, PA317 cells were transfected with either pLin-TGF-beta1 vector or pLin retroviral vector with no TGF-beta1 insert using calcium phosphate precipitation. The latency and bioactivity of TGF-beta1 in conditioned medium derived from transfected PA317 cells were evaluated by enzyme-linked immunosorbent assay and mink lung epithelial cell growth inhibition assay, respectively. The level of latent TGF-beta1 was 13-fold higher (20.1 +/- 0.4 vs. 1.5 +/- 0.03 ng/ml) in conditioned medium from pLin-TGF-beta1 transfected cells than that of control. The latency and bioactivity of TGF-beta1 released from pLin-TGF-beta1 transfected cells were confirmed by evaluation of 3H-thymidine incorporation in Mv1Lu epithelial cells treated with non- and heat-activated 10% conditioned medium. The results showed a significantly lower 3H-thymidine incorporation in Mv1Lu epithelial cells treated with heat-activated PA317 conditioned medium (4% of control) relative to those treated with either control or nonheated conditioned medium. This inhibition was abrogated by addition of 40 microg/ml of TGF-beta1 neutralizing antibody. The level of 3H-thymidine incorporation was then evaluated in MS-9 cells receiving Dulbecco's modified Eagle medium containing either 0% 10%, 30% or 50% volumes of nonactivated PA317 conditioned medium for 24 hours. The results showed a markedly lower proliferation in response to 30% and 50% conditioned medium used in MS-9 cells. Under similar experimental conditions, addition of only mannose 6-phosphate, but not fructose 6-phosphate or mannose 1-phosphate, at 1 mM concentration restored the MS-9 cell proliferative response to latent TGF-beta1. The inhibitory effects of latent TGF-beta1 on MS-9 cell proliferation were restored by addition of either TGF-beta1 neutralizing antibody or cystamine, a transglutaminase inhibitor. In contrast, addition of aprotinin, a plasmin inhibitor, had a marginal influence on inhibitory effects of latent TGF-beta1 on MS-9 cell proliferation. Interestingly, a mixture of latent TGF-beta1 + MS-9 cell membranes, but not MS cell membranes, also inhibited the mink lung epithelial cell proliferation (34% of control). These findings indicate that mannose 6-phosphate/insulin-like growth factor II receptors are involved in latent TGF-beta activation and that is at least partly dependent on cell membrane associated transglutaminase, but not on plasmin.
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PMID:Activation of latent transforming growth factor-beta1 is induced by mannose 6-phosphate/insulin-like growth factor-II receptor. 1120 81