Division of Hematology, Department of Medicine, School of Medicine, University of Utah, Salt Lake City, USA.
Blood. 2010 Apr 8;115(14):2956-9. doi: 10.1182/blood-2009-10-251306. Epub 2010 Feb 2.
Mutations in the iron exporter ferroportin (Fpn) result in iron overload in macrophages or hepatocytes depending upon the mutation. Patients with Fpn mutation D157G show high serum ferritin and normal to slightly elevated transferrin saturation. Here, we show that Fpn(D157G)-green fluorescent protein (GFP) is down-regulated independent of hepcidin, and that this down-regulation is due to the constitutive binding of Jak2 and Fpn phosphorylation. Expression of Fpn(D157G)-GFP in Danio rerio results in a severe growth defect, which can be rescued by iron supplementation. These results identify a hepcidin-independent regulation of Fpn that can result in alterations in iron homeostasis.
铁输出蛋白 Ferroportin（Fpn）突变导致巨噬细胞或肝细胞铁过载，具体取决于突变类型。Fpn 突变 D157G 患者血清铁蛋白升高，转铁蛋白饱和度正常或轻度升高。本研究表明，Fpn(D157G)-绿色荧光蛋白（GFP）的下调独立于铁调素，这一下调是由于 Jak2 的组成性结合和 Fpn 的磷酸化。Fpn(D157G)-GFP 在斑马鱼中的表达导致严重的生长缺陷，而铁补充可挽救这一缺陷。这些结果确定了 Fpn 的一种铁调素非依赖性调节，可能导致铁稳态的改变。
