Abstract
Hepatocyte growth factor activator inhibitor type I (HAI-1) is a membrane-bound, serine protease inhibitor with two protease-inhibitory domains (Kunitz domain I and II). HAI-1 is known as a physiological inhibitor of a membrane-bound serine protease, matriptase. Paradoxically, however, HAI-1 has been found to be required for the extracellular appearance of the protease in an expression system using a monkey kidney COS-1 cell line. In the present study, we show using COS-1 cells that co-expression of recombinant variants of HAI-1 with the inhibition activity toward matriptase, including a variant consisting only of Kunitz domain I (the domain responsible for inhibition of matriptase), allowed for the appearance of this protease in the conditioned medium, whereas that of the variants without the activity did not. These findings suggest that the inhibition activity toward matriptase is critical for the extracellular appearance of protease in COS-1 cells.
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Abbreviations
- HAI-1:
-
Hepatocyte growth factor activator inhibitor type I
- HGF:
-
Hepatocyte growth factor
- HRP:
-
Horseradish peroxidase
- LDLRA domain:
-
Low-density lipoprotein receptor A domain
- MMPs:
-
Matrix metalloproteinases
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Acknowledgments
This study was supported in part by Grants-in-Aid for Scientific Research (Nos. 14658203 and 17380065 to K. I.) from the Japan Society of the Promotion of Sciences. We thank K. Kojima and Seiya Mochida for their technical assistance and advice.
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Miyake, Y., Tsuzuki, S., Yasumoto, M. et al. Requirement of the activity of hepatocyte growth factor activator inhibitor type 1 for the extracellular appearance of a transmembrane serine protease matriptase in monkey kidney COS-1 cells. Cytotechnology 60, 95–103 (2009). https://doi.org/10.1007/s10616-009-9219-7
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DOI: https://doi.org/10.1007/s10616-009-9219-7