Hemojuvelin (HJV) is an important regulator of iron metabolism. Membrane-anchored HJV up-regulates expression of the iron regulatory hormone, hepcidin, through the bone morphogenic protein (BMP) signaling pathway by acting as a BMP co-receptor. HJV can be cleaved by the furin family of proprotein convertases, which releases a soluble form of HJV that suppresses BMP signaling and hepcidin expression by acting as a decoy that competes with membrane HJV for BMP ligands. Recent studies indicate that matriptase-2 binds and degrades HJV, leading to a decrease in cell surface HJV. In the present work, we show that matriptase-2 cleaves HJV at Arg288, which produces one major soluble form of HJV. This shed form of HJV has decreased ability to bind BMP6 and does not suppress BMP6-induced hepcidin expression. These results suggest that the matriptase-2 and proprotein convertase-cleavage products have different roles in the regulation of hepcidin expression.
|Original language||English (US)|
|Number of pages||8|
|Journal||Journal of Biological Chemistry|
|State||Published - Dec 10 2010|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology