Protease nexin-1 complexes and inhibits T cell serine proteinase-1.
The T cell serine proteinase-1 (TSP-1) which most probably is involved in cell killing by cytotoxic T cells is inhibited by protease nexin-1 (PN-1), an extravascular serine protease inhibitor. The inhibition is irreversible and correlates with formation of SDS-stable complexes between the two proteins. Two distinct species of complexes (91 and 122 kDa) are observed upon SDS-PAGE analysis of the reacted proteins, indicating that PN-1 is capable of complexing and inhibiting both subunits of the homodimeric TSP-1 molecule. Heparin (2 micrograms/ml) increases the association rate constant from 4.2 x 10(4) M-1 sec-1 to 4.8 x 10(5) M-1 sec-1. These observations suggest that PN-1 may function as a major extravascular inhibitor of TSP-1 released from cytotoxic T lymphocytes.
Gurwitz
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Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine 92717.
Simon
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Fruth
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Cunningham
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D016564:Amyloid beta-Protein Precursor; D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D046911:Macromolecular Substances; D051379:Mice; D011480:Protease Inhibitors / Q000494:pharmacology*; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors; D058258:Serpin E2; D013379:Substrate Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D046911:Macromolecular Substances; D011480:Protease Inhibitors; D058255:Protease Nexins; D011956:Receptors, Cell Surface; C545486:SERPINE2 protein, human; D015842:Serine Proteinase Inhibitors; D058258:Serpin E2; D006493:Heparin; D012697:Serine Endopeptidases