title: Soluble hemojuvelin is released by proprotein convertase-mediated cleavage at a conserved polybasic RNRR site.
abstract: 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.
authors.affiliation: Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
authors.forename: Lan
authors.initials: L
authors.lastname: Lin
authors.forename: Elizabeta
authors.initials: E
authors.lastname: Nemeth
authors.forename: Julia B
authors.initials: JB
authors.lastname: Goodnough
authors.forename: Dharma R
authors.initials: DR
authors.lastname: Thapa
authors.forename: Victoria
authors.initials: V
authors.lastname: Gabayan
authors.forename: Tomas
authors.initials: T
authors.lastname: Ganz
mesh_terms: D000595:Amino Acid Sequence; D024361:Amino Acids, Basic; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000037:antagonists & inhibitors; D001665:Binding Sites; D002478:Cells, Cultured; D017124:Conserved Sequence; D058851:GPI-Linked Proteins; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D043484:Proprotein Convertases / Q000378:metabolism*; D012995:Solubility
chemical_list: D024361:Amino Acids, Basic; D023181:Antimicrobial Cationic Peptides; D058851:GPI-Linked Proteins; C578702:HAMP protein, human; C481006:HJV protein, human; C579599:Hamp protein, mouse; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D008565:Membrane Proteins; D043484:Proprotein Convertases