Hepsin activates pro‐hepatocyte growth factor and is inhibited by hepatocyte growth factor activator inhibitor‐1B (HAI‐1B) and HAI‐2
- 26 February 2005
- journal article
- Published by Wiley in FEBS Letters
- Vol. 579 (9), 1945-1950
- https://doi.org/10.1016/j.febslet.2005.01.085
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 (IC(50) 21.1+/-2.7 nM) and HAI-2 (IC(50) 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.Keywords
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