Source:http://linkedlifedata.com/resource/pubmed/id/10496984
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions |
umls-concept:C0011602,
umls-concept:C0016016,
umls-concept:C0019134,
umls-concept:C0040048,
umls-concept:C0071196,
umls-concept:C0331858,
umls-concept:C0441655,
umls-concept:C0475264,
umls-concept:C1314939,
umls-concept:C1420706,
umls-concept:C1704259,
umls-concept:C1704640,
umls-concept:C1704675,
umls-concept:C1705987,
umls-concept:C1706515
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| pubmed:issue |
1
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| pubmed:dateCreated |
1999-11-8
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| pubmed:abstractText |
Human tissue factor pathway inhibitor-2 (TFPI-2)/matrix-associated serine protease inhibitor (MSPI), a Kunitz-type serine protease inhibitor, inhibits plasmin, trypsin, chymotrypsin, plasma kallikrein, cathepsin G, and factor VIIa-tissue factor complex. The mature protein has a molecular mass of 32-33 kDa, but exists in vivo as two smaller, underglycosylated species of 31 and 27 kDa. TFPI-2/MSPI triplet is synthesized and secreted by a variety of cell types that include epithelial, endothelial, and mesenchymal cells. Because the majority (75-90%) of TFPI-2/MSPI is associated with the extracellular matrix (ECM), we examined which components of the ECM bind TFPI-2/MSPI. We found that TFPI-2/MSPI bound specifically to heparin and dermatan sulfate. Interaction of these two glycosaminoglycans (GAGs) with TFPI-2/MSPI involved one or more common protein domains, as evidenced by cross-competition experiments. However, binding affinity for TFPI-2/MSPI with heparin was 250-300 times greater than that for TFPI-2/MSPI with dermatan sulfate. Binding of TFPI-2/MSPI to GAGs was inhibited by NaCl or arginine but not by glucose, mannose, galactose, 6-aminohexanoic acid, or urea, suggesting that arginine-mediated ionic interactions participate in the GAG binding of TFPI-2/MSPI. This supposition was supported by the observation that only NaCl or arginine could elute the TFPI-2/MSPI protein triplet from an ECM derived from human dermal fibroblasts. Reduced TFPI-2/MSPI did not bind to heparin, suggesting that proper disulfide pairings and conformation are essential for matrix binding. To determine whether heparin modulates the activity of TFPI-2/MSPI, we determined the rate of inhibition of plasmin by the inhibitor with and without heparin and found that TFPI-2/MSPI is more active in the presence of heparin. Collectively, our results demonstrate that conformation-dependent arginine-mediated ionic interactions are responsible for the TFPI-2/MSPI triplet binding to fibroblast ECM, heparin, and dermatan sulfate and that heparin augmented the rate of inhibition of plasmin by TFPI-2/MSPI.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Arginine,
http://linkedlifedata.com/resource/pubmed/chemical/CTSG protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cathepsin G,
http://linkedlifedata.com/resource/pubmed/chemical/Cathepsins,
http://linkedlifedata.com/resource/pubmed/chemical/Chymotrypsin,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Dermatan Sulfate,
http://linkedlifedata.com/resource/pubmed/chemical/Fibrinolysin,
http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Heparin,
http://linkedlifedata.com/resource/pubmed/chemical/Kallikreins,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Pregnancy Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Trypsin,
http://linkedlifedata.com/resource/pubmed/chemical/cancer procoagulant,
http://linkedlifedata.com/resource/pubmed/chemical/tissue-factor-pathway inhibitor 2
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
0003-9861
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright 1999 Academic Press.
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| pubmed:issnType |
Print
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| pubmed:day |
1
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| pubmed:volume |
370
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
112-8
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:10496984-Arginine,
pubmed-meshheading:10496984-Binding, Competitive,
pubmed-meshheading:10496984-Cathepsin G,
pubmed-meshheading:10496984-Cathepsins,
pubmed-meshheading:10496984-Chymotrypsin,
pubmed-meshheading:10496984-Cysteine Endopeptidases,
pubmed-meshheading:10496984-Dermatan Sulfate,
pubmed-meshheading:10496984-Fibrinolysin,
pubmed-meshheading:10496984-Glycoproteins,
pubmed-meshheading:10496984-Heparin,
pubmed-meshheading:10496984-Humans,
pubmed-meshheading:10496984-Kallikreins,
pubmed-meshheading:10496984-Kinetics,
pubmed-meshheading:10496984-Neoplasm Proteins,
pubmed-meshheading:10496984-Pregnancy Proteins,
pubmed-meshheading:10496984-Serine Endopeptidases,
pubmed-meshheading:10496984-Serine Proteinase Inhibitors,
pubmed-meshheading:10496984-Trypsin
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| pubmed:year |
1999
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| pubmed:articleTitle |
Matrix localization of tissue factor pathway inhibitor-2/matrix-associated serine protease inhibitor (TFPI-2/MSPI) involves arginine-mediated ionic interactions with heparin and dermatan sulfate: heparin accelerates the activity of TFPI-2/MSPI toward plasmin.
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| pubmed:affiliation |
Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, 77030, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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