Meta-Biol

• Pathways

Hepsin (HPN, aka TMPRSS1) is a cell surface-expressed chymotrypsin-like serine protease and a member of the family of type II transmembrane serine proteases (TTSP). The HPN zymogen is activated autocatalytically by cleavage at Arg162-Ile163, forming a heterodimeric enzyme (Tsuji et al. 1991, Torres-Rosado et al. 1993). HPN plays an essential role in cell growth and maintenance of cell morphology and is highly upregulated in prostate cancer and promotes tumor progression and metastasis (Klezovitch et al. 2004). Located on the cell surface, HPN can activate fibrinolytic enzymes, matrix metalloproteases and latent forms of growth factors, such as hepatocyte growth factor (HGF). HGF is a pleiotropic factor and activates hepatocyte growth factor receptor (MET). HGF is secreted into the extracellular matrix as an inactive single chain precursor (pro-HGF (32-728)) and requires cleavage at Arg494–Val495 to form the biologically active alpha-beta heterodimer (Hartmann et al. 1992, Kirchhofer et al. 2005). The Kunitz-type protease inhibitors 1 and 2 (SPINT1 and 2, aka HAI1 and 2) are inhibitors of HPN activity (Kawaguchi et al. 1997, Shimomoura et al. 1997, Kirchhofer et al. 2005).