| The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin. | |
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MedLine Citation:
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PMID: 18976966 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The liver peptide hepcidin regulates body iron, is upregulated in iron overload and inflammation, and is downregulated in iron deficiency/hypoxia. The transmembrane serine protease matriptase-2 (TMPRSS6) inhibits the hepcidin response and its mutational inactivation causes iron-deficient anemia in mice and humans. Here we confirm the inhibitory effect of matriptase-2 on hepcidin promoter; we show that matriptase-2 lacking the serine protease domain, identified in the anemic Mask mouse (matriptase-2(MASK)), is fully inactive and that mutant R774C found in patients with genetic iron deficiency has decreased inhibitory activity. Matriptase-2 cleaves hemojuvelin (HJV), a regulator of hepcidin, on plasma membrane; matriptase-2(MASK) shows no cleavage activity and the human mutant only partial cleavage capacity. Matriptase-2 interacts with HJV through the ectodomain since the interaction is conserved in matriptase-2(MASK). The expression of matriptase-2 mutants in zebrafish results in anemia, confirming the matriptase-2 role in iron metabolism and its interaction with HJV. |
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Authors:
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Laura Silvestri; Alessia Pagani; Antonella Nai; Ivana De Domenico; Jerry Kaplan; Clara Camaschella |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-10-30 |
Journal Detail:
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Title: Cell metabolism Volume: 8 ISSN: 1932-7420 ISO Abbreviation: Cell Metab. Publication Date: 2008 Dec |
Date Detail:
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Created Date: 2008-12-01 Completed Date: 2009-01-15 Revised Date: 2011-11-24 |
Medline Journal Info:
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Nlm Unique ID: 101233170 Medline TA: Cell Metab Country: United States |
Other Details:
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Languages: eng Pagination: 502-11 Citation Subset: IM |
Affiliation:
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Vita-Salute San Raffaele University, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele, Milan, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Substitution Animals Antimicrobial Cationic Peptides / antagonists & inhibitors*, biosynthesis, metabolism Cell Membrane / metabolism Cells, Cultured Endoplasmic Reticulum / metabolism GPI-Linked Proteins HeLa Cells Humans Membrane Proteins / biosynthesis, metabolism* Promoter Regions, Genetic Protein Processing, Post-Translational Serine Endopeptidases / biosynthesis, metabolism* Signal Transduction Zebrafish |
| Grant Support | |
ID/Acronym/Agency:
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DK 070947/DK/NIDDK NIH HHS; GGP08089//Telethon; R01 DK070947-04/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antimicrobial Cationic Peptides; 0/GPI-Linked Proteins; 0/HFE2 protein, human; 0/Membrane Proteins; 0/hepcidin; EC 3.4.21.-/Serine Endopeptidases; EC 3.4.21.-/TMPRSS6 protein, human |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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