scholarly journals Potent Inhibition and Global Co-localization Implicate the Transmembrane Kunitz-type Serine Protease Inhibitor Hepatocyte Growth Factor Activator Inhibitor-2 in the Regulation of Epithelial Matriptase Activity

2008 ◽  
Vol 283 (43) ◽  
pp. 29495-29504 ◽  
Author(s):  
Roman Szabo ◽  
John P. Hobson ◽  
Karin List ◽  
Alfredo Molinolo ◽  
Chen-Yong Lin ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Protease Inhibitor ◽  
Serine Protease ◽  
Serine Protease Inhibitor ◽  
Potent Inhibition ◽  
Hepatocyte Growth Factor Activator ◽  
Kunitz Type ◽  
Hepatocyte Growth ◽  
Activator Inhibitor

scholarly journals Hepatocyte Growth Factor Activator Inhibitor, a Novel Kunitz-type Serine Protease Inhibitor

1997 ◽  
Vol 272 (10) ◽  
pp. 6370-6376 ◽  
Author(s):  
Takeshi Shimomura ◽  
Kimitoshi Denda ◽  
Akiko Kitamura ◽  
Toshiya Kawaguchi ◽  
Masahiro Kito ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Protease Inhibitor ◽  
Serine Protease ◽  
Serine Protease Inhibitor ◽  
Hepatocyte Growth Factor Activator ◽  
Kunitz Type ◽  
Hepatocyte Growth ◽  
Activator Inhibitor

scholarly journals Hepatocyte growth factor activator inhibitor-1 has a complex subcellular itinerary

2008 ◽  
Vol 413 (2) ◽  
pp. 251-259 ◽  
Author(s):  
Sine Godiksen ◽  
Joanna Selzer-Plon ◽  
Esben D. K. Pedersen ◽  
Kathrine Abell ◽  
Hanne B. Rasmussen ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Hepatocyte Growth Factor ◽  
Serine Protease ◽  
Apical Plasma Membrane ◽  
Hepatocyte Growth Factor Activator ◽  
Basolateral Plasma Membrane ◽  
Hepatocyte Growth ◽  
Activator Inhibitor

HAI-1 [HGF (hepatocyte growth factor) activator inhibitor-1] is a Kunitz-type transmembrane serine protease inhibitor that forms inhibitor complexes with the trypsin-like serine protease, matriptase. HAI-1 is essential for mouse placental development and embryo survival and together with matriptase it is a key regulator of carcinogenesis. HAI-1 is expressed in polarized epithelial cells, which have the plasma membrane divided by tight junctions into an apical and a basolateral domain. In the present study we show that HAI-1 at steady-state is mainly located on the basolateral membrane of both Madin–Darby canine kidney cells and mammary gland epithelial cells. After biosynthesis, HAI-1 is exocytosed mainly to the basolateral plasma membrane from where 15% of the HAI-1 molecules are proteolytically cleaved and released into the basolateral medium. The remaining membrane-associated HAI-1 is endocytosed and then recycles between the basolateral plasma membrane and endosomes for hours until it is transcytosed to the apical plasma membrane. Minor amounts of HAI-1 present at the apical plasma membrane are proteolytically cleaved and released into the apical medium. Full-length membrane-bound HAI-1 has a half-life of 1.5 h and is eventually degraded in the lysosomes, whereas proteolytically released HAI-1 is more stable. HAI-1 is co-localized with its cognate protease, matriptase, at the basolateral plasma membrane. We suggest that HAI-1, in addition to its protease inhibitory function, plays a role in transporting matriptase as a matriptase–HAI-1 complex from the basolateral plama membrane to the apical plasma membrane, as matriptase is known to interact with prostasin, located at the apical plasma membrane.

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