Linked Life Data

9261109

Source:http://linkedlifedata.com/resource/pubmed/id/9261109

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
34
pubmed:dateCreated
1997-9-15
pubmed:abstractText
Increased production of proteinases, such as matrix metalloproteinases (MMPs), is a characteristic feature of malignant tumors. Some human cancers and cell lines derived from them also express trypsinogen, but the function of the extrapancreatic trypsin has remained unclear. In this study we cloned and sequenced trypsinogen-2 cDNA from human COLO 205 colon carcinoma cells and characterized the ability of the enzyme to activate latent human type IV procollagenases (proMMP-2 and proMMP-9). As shown by cloning and N-terminal amino acid sequencing, the amino acid sequence of tumor-associated trypsin-2 is identical to that of pancreatic trypsin-2. We found that both pancreatic trypsin-2 and tumor cell-derived trypsin-2 are efficient activators of proMMP-9 and are capable of activating proMMP-9 at a molar ratio of 1:1000, the lowest reported so far. Human trypsin-2 was a more efficient activator than widely used bovine trypsin and converted the 92-kDa proMMP-9 to a single 77-kDa product that was not fragmented further. The single peptide bond cleaved by trypsin-2 in proMMP-9 was Arg87-Phe88. The generation of the 77-kDa species coincided with the increase in specific activity of MMP-9. In contrast, trypsin-2 only partially activated proMMP-2. Trypsin-2 cleaved the Arg99-Lys100 peptide bond of proMMP-2 generating 62-65-kDa MMP-2 species. Trypsin-2-induced proMMP-2 and -9 conversions were inhibited by tumor-associated trypsin inhibitor added either prior to or during activation indicating that proMMPs were not activated autocatalytically. Trypsin-2 also activated proMMPs associated with tissue inhibitor of matrix metalloproteinases, the complexes of which are thought to be the major MMP forms in vivo. The ability of human tumor cell-derived trypsin-2 to activate latent MMPs suggests a role for trypsin-2 in initiating the proteinase cascade that mediates tumor invasion and metastasis formation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Collagenases, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Precursors, http://linkedlifedata.com/resource/pubmed/chemical/Gelatinases, http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 2, http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 9, http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases, http://linkedlifedata.com/resource/pubmed/chemical/PRSS2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Trypsin, http://linkedlifedata.com/resource/pubmed/chemical/Trypsin Inhibitor, Kazal Pancreatic, http://linkedlifedata.com/resource/pubmed/chemical/Trypsin Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Trypsinogen, http://linkedlifedata.com/resource/pubmed/chemical/procollagenase
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
272
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
21067-74
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Activation of type IV procollagenases by human tumor-associated trypsin-2.
pubmed:affiliation
Departments of Medical Chemistry and Periodontology, University of Helsinki, FIN-00014 Helsinki, Finland. tsorsa@hammas.helsinki.fi
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't