In:
Traffic, Wiley, Vol. 18, No. 6 ( 2017-06), p. 378-391
Abstract:
It has recently been shown that hepatocyte growth factor activator inhibitor‐2 ( HAI ‐2) is able to suppress carcinogenesis induced by overexpression of matriptase, as well as cause regression of individual established tumors in a mouse model system. However, the role of HAI ‐2 is poorly understood. In this study, we describe 3 mutations in the binding loop of the HAI ‐2 Kunitz domain 1 ( K42N , C47F and R48L ) that cause a delay in the SEA domain cleavage of matriptase, leading to accumulation of non‐ SEA domain cleaved matriptase in the endoplasmic reticulum ( ER ). We suggest that, like other known SEA domains, the matriptase SEA domain auto‐cleaves and reflects that correct oligomerization, maturation, and/or folding has been obtained. Our results suggest that the HAI ‐2 Kunitz domain 1 mutants influence the flux of matriptase to the plasma membrane by affecting the oligomerization, maturation and/or folding of matriptase, and as a result the SEA domain cleavage of matriptase. Two of the HAI ‐2 Kunitz domain 1 mutants investigated ( C47F , R48L and C47F / R48L ) also displayed a reduced ability to proteolytically silence matriptase. Hence, HAI ‐2 separately stabilizes matriptase, regulates the secretory transport, possibly via maturation/oligomerization and inhibits the proteolytic activity of matriptase in the ER , and possible throughout the secretory pathway.
Type of Medium:
Online Resource
ISSN:
1398-9219
,
1600-0854
DOI:
10.1111/tra.2017.18.issue-6
Language:
English
Publisher:
Wiley
Publication Date:
2017
detail.hit.zdb_id:
2020962-9
SSG:
12
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