[HTML][HTML] Hepsin activates pro-hepatocyte growth factor and is inhibited by hepatocyte growth factor activator inhibitor-1B (HAI-1B) and HAI-2

D Kirchhofer, M Peek, MT Lipari, K Billeci, B Fan… - FEBS letters, 2005 - Elsevier
D Kirchhofer, M Peek, MT Lipari, K Billeci, B Fan, P Moran
FEBS letters, 2005Elsevier
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 …
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±2.7nM) and HAI-2 (IC50 1.3±0.3nM). 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.
Elsevier