Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2051729 | FEBS Letters | 2005 | 6 Pages |
Abstract
Hepsin, a type II transmembrane serine protease, is highly upregulated in prostate cancer and promotes tumor progression and metastasis. We generated a soluble form of hepsin comprising the entire extracellular domain to show that it efficiently converts single-chain hepatocyte growth factor (pro-HGF) into biologically active two-chain HGF. Hepsin activity was potently inhibited by soluble forms of the bi-Kunitz domain inhibitors HAI-1B (IC50 21.1 ± 2.7 nM) and HAI-2 (IC50 1.3 ± 0.3 nM). Enzymatic assays with HAI-1B Kunitz domain mutants (R260A and K401A) further demonstrated that inhibition was due to Kunitz domain-1. The results suggest a functional link between hepsin and the HGF/Met pathway, which may contribute to tumor progression.
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Authors
Daniel Kirchhofer, Mark Peek, Michael T. Lipari, Karen Billeci, Bin Fan, Paul Moran,