Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 285, Issue 50, Pages 39021-39028Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M110.183160
Keywords
-
Categories
Funding
- National Institutes of Health [DK080765, DK72166, T32 HD049309]
- Vertex Pharmaceuticals
- American Heart Association [10PRE3530017]
Ask authors/readers for more resources
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 Arg(288), 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available