Soluble hemojuvelin is released by proprotein convertase-mediated cleavage at a conserved polybasic RNRR site

被引：81

作者：

Lin, Lan ^{[2
]}

Nemeth, Elizabeta ^{[1
]}

Goodnough, Julia B. ^{[2
]}

Thapa, Dharma R. ^{[1
]}

Gabayan, Victoria ^{[1
]}

Ganz, Tomas ^{[1
,2
]}

机构：

[1] Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA

来源：

BLOOD CELLS MOLECULES AND DISEASES | 2008年 / 40卷 / 01期

关键词：

hepcidin; iron; furin convertase inhibitor; GPI anchor; repulsive guidance molecule C;

D O I：

10.1016/j.bcmd.2007.06.023

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

As the principal iron-regulatory hormone, hepcidin plays an important role in systemic iron homeostasis. The regulation of hepcidin expression by iron loading appears to be unexpectedly complex and has attracted much interest. The GPI-linked membrane protein hemojuvelin (GPI-hemojuvelin) is an essential upstream regulator of hepcidin expression. A soluble form of hemojuvelin (s-hemojuvelin) exists in blood and acts as antagonist of GPI-hemojuvelin to downregulate hepcidin expression. The release of s-hemojuvelin is negatively regulated by both transferrin-bound iron (holo-Tf) and non-transferrin-bound iron (FAC), indicating s-hemojuvelin could be one of the mediators of hepcidin regulation by iron. In this report, we investigate the proteinase involved in the release of s-hemojuvelin and show that s-hemojuvelin is released by a proprotein convertase through the cleavage at a conserved polybasic RNRR site. (C) 2007 Elsevier Inc. All rights reserved.

引用

页码：122 / 131

页数：10

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