Reactome | HPN heterodimer cleaves pro-HGF to form HGF dimer

HPN heterodimer cleaves pro-HGF to form HGF dimer

Stable Identifier

R-HSA-6800200

Type

Reaction [transition]

Species

Homo sapiens

Compartment

extracellular region, plasma membrane

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HPN heterodimer cleaves pro-HGF to form HGF dimer

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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).

Literature References

PubMed ID	Title	Journal	Year
15324701	Hepsin promotes prostate cancer progression and metastasis Klezovitch, O, Chevillet, J, Mirosevich, J, Roberts, RL, Matusik, RJ, Vasioukhin, V	Cancer Cell	2004
9346890	Purification and cloning of hepatocyte growth factor activator inhibitor type 2, a Kunitz-type serine protease inhibitor Kawaguchi, T, Qin, L, Shimomura, T, Kondo, J, Matsumoto, K, Denda, K, Kitamura, N	J. Biol. Chem.	1997
15792801	Hepsin activates pro-hepatocyte growth factor and is inhibited by hepatocyte growth factor activator inhibitor-1B (HAI-1B) and HAI-2 Kirchhofer, D, Peek, M, Lipari, MT, Billeci, K, Fan, B, Moran, P	FEBS Lett.	2005
8346233	Hepsin, a putative cell-surface serine protease, is required for mammalian cell growth Torres-Rosado, A, O'Shea, KS, Tsuji, A, Chou, SH, Kurachi, K	Proc. Natl. Acad. Sci. U.S.A.	1993
9045658	Hepatocyte growth factor activator inhibitor, a novel Kunitz-type serine protease inhibitor Shimomura, T, Denda, K, Kitamura, A, Kawaguchi, T, Kito, M, Kondo, J, Kagaya, S, Qin, L, Takata, H, Miyazawa, K, Kitamura, N	J. Biol. Chem.	1997
1885621	Hepsin, a cell membrane-associated protease. Characterization, tissue distribution, and gene localization Tsuji, A, Torres-Rosado, A, Arai, T, Le Beau, MM, Lemons, RS, Chou, SH, Kurachi, K	J. Biol. Chem.	1991
1280830	A functional domain in the heavy chain of scatter factor/hepatocyte growth factor binds the c-Met receptor and induces cell dissociation but not mitogenesis Hartmann, G, Naldini, L, Weidner, KM, Sachs, M, Vigna, E, Comoglio, PM, Birchmeier, W	Proc. Natl. Acad. Sci. U.S.A.	1992