Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.2.1.23 (
beta-galactosidase
)
14,648
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Hepatocyte growth factor activator inhibitors (HAI)-1 and -2 are recently identified and closely related Kunitz-type transmembrane serine protease inhibitors. Whereas HAI-1 is well established as an inhibitor of the serine proteases matriptase and hepatocyte growth factor activator, the physiological targets of
HAI-2
are unknown. Here we show that
HAI-2
displays potent inhibitory activity toward matriptase, forms SDS-stable complexes with the serine protease, and blocks matriptase-dependent activation of its candidate physiological substrates proprostasin and cell surface-bound pro-urokinase plasminogen activator. To further explore the potential functional relationship between
HAI-2
and matriptase, we generated a transgenic mouse strain with a promoterless
beta-galactosidase
marker gene inserted into the endogenous locus encoding
HAI-2
protein and performed a global high resolution mapping of the expression of
HAI-2
, matriptase, and HAI-1 proteins in all adult tissues. This analysis showed striking co-localization of
HAI-2
with matriptase and HAI-1 in epithelial cells of all major organ systems, thus strongly supporting a role of
HAI-2
as a physiological regulator of matriptase activity, possibly acting in a redundant or partially redundant manner with HAI-1. Unlike HAI-1 and matriptase, however,
HAI-2
expression was also detected in non-epithelial cells of brain and lymph nodes, suggesting that
HAI-2
may also be involved in inhibition of serine proteases other than matriptase.
...
PMID: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. 1871 50
