Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.9 (enterokinase)
 675 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proteinase species secreted by 10 human gastric carcinoma cell lines were analyzed by gelatin zymography and immunoblotting. These cell lines were classified into the following three groups with respect to proteinase secretion: cell lines secreting mainly gelatinases A and/or B; those secreting multiple types of serine proteinases; and those scarcely secreting these enzymes. Two cell lines of the second group, STKM-1 and MKN28, hardly secreted metalloproteinases but secreted the following four types of serine proteinases: (a) two trypsin-like enzymes (M(r) 26,000 and 24,000 in proenzyme forms); (b) a tissue kallikrein-like enzyme (M(r) 150,000 in a complex form); (c) a plasmin-like enzyme (M(r) 70,000); and (d) a plasminogen activator (urokinase-type, M(r) 57,000, from STKM-1 and tissue-type, M(r) 70,000, from MKN28). The M(r) 70,000 plasmin-like enzyme was also detected at lower levels in the conditioned media of four other cell lines (MKN1, MKN45, NUGC-3, and KATO III). The M(r) 24,000 proenzyme of the trypsin-like enzyme was purified from the serum-free conditioned medium of STKM-1. The proenzyme was activated by enterokinase treatment or autolytically by incubation at neutral pH, decreasing its apparent molecular weight from 24,000 to 23,000 on nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The activated enzyme extensively degraded fibronectin, laminin, and gelatins and to lesser extents type I, III, IV, and V collagens at 30 degrees C. These results suggest that the matrix serine proteinases may play a major role in the matrix degradation by some kinds of human cancer cells.
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PMID:Multiple secretion of matrix serine proteinases by human gastric carcinoma cell lines. 138 87

We have recently demonstrated that many cancer cell lines produce a novel trypsinogen isoenzyme called tumor-associated trypsinogen 2 (TAT-2). It was found during a search of the target protease for tumor-associated trypsin inhibitor (TATI). We now show that degradation of subendothelial cell extracellular matrix (ECM) by four different cell lines (COLO 205 colon carcinoma, K-562 erythroleukemia, CAPAN-1 pancreatic carcinoma, and HT 1080 fibrosarcoma) can be partially inhibited by TATI or neutralizing trypsin antibodies. When cells were cultured in serum-free medium on ECM, TATI and trypsin antibodies inhibited the release of immunoreactive fibronectin fragments from ECM by 47-54 and 40%, respectively. Degradation of isotopically labeled ([3H]serine, [3H]proline, and [35S]sulfate) ECM was also significantly prevented by TATI. At its maximum, it exerted a 57% inhibition on the degradation of [3H]serine-labeled ECM. Plasminogen added exogenously to the culture medium further potentiated the proteolysis of ECM. Interestingly, addition of enteropeptidase, an activator of TAT-2, also enhanced cell-mediated proteolysis as assessed by degradation of purified fibronectin coated onto the surface of wells. Immunoblot analysis showed that enteropeptidase-mediated proteolysis generated a pattern of fibronectin fragments similar to that obtained by digestion of purified fibronectin by TAT-2. These results demonstrate the existence of a proteolytic system in tumor cells which is dependent on the activation of TAT-2. We suggest that TAT-2 is involved in a protease cascade-stimulating tumor cell invasion and degradation of extracellular matrix.
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PMID:Tumor-associated trypsin participates in cancer cell-mediated degradation of extracellular matrix. 200 30

It has previously been reported that the trypsinogen gene is expressed in various human cancers. To investigate the possible role of trypsin in tumor malignancy, trypsinogen-1 cDNA was introduced into the human gastric carcinoma cell line MKN-1. The overexpression of trypsinogen-1 in MKN-1 cells stimulated cellular growth and adhesion to fibronectin and vitronectin when the trypsinogen activator enterokinase was added into the culture. Enterokinase treatment of the conditioned medium of the MKN-1 transfectants partially converted the proforms of gelatinases B and A to their apparent active forms. When the MKN-1 transfectants expressing trypsinogen-1 were intraperitoneally transplanted into nude mice, the mice frequently produced tumors in the colon, spleen and liver. However, the mice implanted with control MKN-1 cells produced no tumors. These results strongly suggest that tumor-derived trypsin contributes to the disseminated growth of some types of cancer cells including gastric cancer.
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PMID:Stimulation of cellular growth and adhesion to fibronectin and vitronectin in culture and tumorigenicity in nude mice by overexpression of trypsinogen in human gastric cancer cells. 993 8

Heparan sulfate proteoglycans expressed on the Xenopus animal cap ectoderm have been implicated in transmitting left-right information to heart and gut primordia. We report here that syndecan-2 functions in the ectoderm to mediate cardiac and visceral situs, upstream of known asymmetrically expressed genes but independently of its ability to mediate fibronectin fibrillogenesis. Left-right development is dependent on a distinct subset of glycosaminoglycan attachment sites on syndecan-2. A novel in vivo approach with enterokinase demonstrates that syndecan-2 functions in left-right patterning during early gastrulation. We describe a cell-nonautonomous role for ectodermal syndecan-2 in transmitting left-right information to migrating mesoderm. The results further suggest that this function may be related to the transduction of Vg1-related signals.
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PMID:Ectodermal syndecan-2 mediates left-right axis formation in migrating mesoderm as a cell-nonautonomous Vg1 cofactor. 1178 19

TTSPs [type II TMPRSSs (transmembrane serine proteases)] are a growing family of trypsin-like enzymes with, in some cases, restricted tissue distribution. To investigate the expression of TTSPs in the nervous system, we performed a PCR-based screening approach with P10 (postnatal day 10) mouse spinal cord mRNA. We detected the expression of five known TTSPs and identified a novel TTSP, which we designated neurobin. Neurobin consists of 431 amino acids. In the extracellular part, neurobin contains a single SEA (sea-urchin sperm protein, enterokinase and agrin) domain and a C-terminal serine protease domain. RT-PCR (reverse transcription-PCR) analysis indicated the expression of neurobin in spinal cord and cerebellum. Histochemical analysis of brain sections revealed distinct staining of Purkinje neurons of the cerebellum. Transiently overexpressed neurobin was autocatalytically processed and inserted into the plasma membrane. Autocatalytic activation could be suppressed by mutating Ser(381) in the catalytic pocket to an alanine residue. The protease domain of neurobin, produced in Escherichia coli and refolded from inclusion bodies, cleaved chromogenic peptides with an arginine residue in position P(1). Serine protease inhibitors effectively suppressed the proteolytic activity of recombinant neurobin. Ca2+ or Na+ ions did not significantly modulate the catalytic activity of the protease. Recombinant neurobin processed 17-kDa FGF-2 (fibroblast growth factor-2) at several P(1) lysine and arginine positions to distinct fragments, in a heparin-inhibitable manner, but did not cleave FGF-7, laminin or fibronectin. These results indicate that neurobin is an authentic TTSP with trypsin-like activity and is able to process FGF-2 in vitro.
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PMID:Neurobin/TMPRSS11c, a novel type II transmembrane serine protease that cleaves fibroblast growth factor-2 in vitro. 1821 25