Epithin/PRSS14, a type II transmembrane serine protease, plays critical roles in cancer metastasis. Previously, we have reported that epithin/PRSS14 undergoes ectodomain shedding in response to phorbol myristate acetate (PMA) stimulation. In this study, we show that transforming growth factor-β (TGF-β) induces rapid epithin/PRSS14 shedding through receptor mediated pathway in 427.1.86 thymoma cells. Tumor necrosis factor-α converting enzyme (TACE) is responsible for this shedding. Amino acid sequence encompassing the putative shedding cleavage site of epithin/PRSS14 exhibit strong homology to the cleavage site of l-selectin, a known TACE substrate. TACE inhibitor, TAPI-0 and TACE siRNA greatly reduced TGF-β-induced epithin/PRSS14 shedding. TGF-β treatment induces translocation of intracellular pool of TACE to the membrane where epithin/PRSS14 resides. These findings suggest that TGF-β induces epithin/PRSS14 shedding by mediating translocation of epithin/PRSS14 sheddase, TACE, to the membrane.
|Number of pages
|Biochemical and biophysical research communications
|Published - 2014 Oct 3
Bibliographical noteFunding Information:
This work was supported by the Grant from the National Research Foundation of Korea ( NRF-2011-0009555 ) to D.P. and by Inha University Research Grant and the Korea Healthcare Technology R&D Project ( A111927 ), Ministry of Health & Welfare to M.G.K. H.S.L., B.M.P., and Y.C. were the recipients of the BK21 fellowship. None of the authors of this work has financial interest related to this work.
- Ectodomain shedding
- Tumor necrosis factor-α converting enzyme (TACE)
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology