Matriptase-2- and proprotein convertase-cleaved forms of hemojuvelin have different roles in the down-regulation of hepcidin expression

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48 Scopus citations

Abstract

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 languageEnglish (US)
Pages (from-to)39021-39028
Number of pages8
JournalJournal of Biological Chemistry
Volume285
Issue number50
DOIs
StatePublished - Dec 10 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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