Lee Pauline
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037, USA.
Acta Haematol. 2009;122(2-3):87-96. doi: 10.1159/000243792. Epub 2009 Nov 10.
Iron, an essential element for life, is regulated primarily at the level of uptake, storage, and transport in order to maintain sufficient availability for normal physiology. The key protein in iron homeostasis is a 25-amino-acid peptide, hepcidin, which modulates the amount of iron in the circulation by binding and promoting the degradation of the iron exporter ferroportin. Given the central importance of hepcidin, recent studies have focused on how iron is sensed and how the iron signal is transmitted to hepcidin. Mutations in a type II serine protease, matriptase-2/TMPRSS6, were recently identified to be associated with severe iron deficiency caused by inappropriately high levels of hepcidin expression. A key biologically relevant substrate for the proteolytic activity of matriptase-2/TMPRSS6 was found to be hemojuvelin, a cell surface protein that regulates hepcidin expression through a BMP/SMAD pathway. In this review, we discuss the putative role of matriptase-2/TMPRSS6 in iron homeostasis.
铁作为生命必需元素，主要在摄取、储存和运输水平上受到调节，以维持正常生理功能所需的充足供应。铁稳态中的关键蛋白是一种由25个氨基酸组成的肽——铁调素，它通过结合并促进铁输出蛋白铁转运蛋白的降解来调节循环中的铁含量。鉴于铁调素的核心重要性，近期研究聚焦于铁的感知方式以及铁信号如何传递至铁调素。最近发现，II型丝氨酸蛋白酶matriptase-2/TMPRSS6的突变与因铁调素表达水平异常升高导致的严重缺铁有关。matriptase-2/TMPRSS6蛋白水解活性的一个关键生物学相关底物是血色素沉着症相关蛋白，这是一种通过骨形态发生蛋白/信号转导分子和转录激活因子（BMP/SMAD）途径调节铁调素表达的细胞表面蛋白。在本综述中，我们讨论了matriptase-2/TMPRSS6在铁稳态中的假定作用。
