Molecular Cloning of Transferrin Receptor 2

Kawabata, Hiroshi; Yang, Rong; Hirama, Toshiyasu; Vuong, Peter T.; Kawano, S.; Gombart, Adrian F.; Koeffler, H. Phillip

doi:10.1074/jbc.274.30.20826

Cited by 557 publications

(174 citation statements)

References 30 publications

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“…A likely explanation for the lack of change in TfR mRNA expression would be the existence of TfR2 in the liver. Kawabata et al 56 recently identified TfR2 in the human liver, and the mouse homolog has since been found in the mouse liver. 57 TfR2 was highly expressed in the mouse liver compared with low TfR expression.…”

Section: Discussionmentioning

confidence: 99%

Deregulation of iron homeostasis and cold-preservation injury to rat liver stored in University of Wisconsin solution

Wyllie¹

2003

Liver Transplantation

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Very little is known about iron metabolism and the mediators of iron metabolism in liver subjected to cold storage before transplantation. Therefore, in this study, we investigated the effect of cold storage on iron homeostasis in the rat liver. When livers were stored at 4°C in University of Wisconsin solution for up to 6 and 24 hours, significant increases occurred in the labile iron pool, ferritin protein, and heme oxygenase activity. Significant decreases in heme content and iron regulatory protein 1 and 2 binding activities occurred by 24 hours. Liver injury indicated by significant increases in University of Wisconsin solution transaminase activity and liver lipid hydroperoxide levels occurred by 6 and 24 hours. Taken together, these results suggest that during pretransplantation cold storage of the liver, an aberrant iron homeostasis develops that contributes to preservation injury, and predisposes the liver to reperfusion injury by iron-dependent reactive oxygen species/Fenton reaction. (Liver Transpl 2003;9:401-410.)

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Section: Discussionmentioning

confidence: 99%

Deregulation of iron homeostasis and cold-preservation injury to rat liver stored in University of Wisconsin solution

Wyllie¹

2003

Liver Transplantation

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“…TfR1 is ubiquitously expressed in most cell types with the notable exception of mature erythroid cells, whereas TfR2 is predominantly expressed in the liver (1)(2)(3). Like TfR1, TfR2 binds transferrin (Tf) in a pH-dependent manner but with 25-fold lower affinity and delivers iron to cells (4,5). The regulation of TfR1 and TfR2 is distinctly different.…”

Section: Transferrin (Tf)mentioning

confidence: 99%

The Cytoplasmic Domain of Transferrin Receptor 2 Dictates Its Stability and Response to Holo-transferrin in Hep3B Cells

Chen

Enns

2007

Journal of Biological Chemistry

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Transferrin receptor 2 (TfR2) is a homolog of transferrin receptor 1 (TfR1), the receptor responsible for the uptake of iron-loaded transferrin (holo-Tf) into cells. Unlike the ubiquitous TfR1, TfR2 is predominantly expressed in the liver. Mutations in TfR2 gene cause a rare autosomal recessive form of the iron overload disease, hereditary hemochromatosis. Previous studies demonstrated that holo-Tf increases TfR2 levels by stabilizing TfR2 at the protein level. In this study we constructed two chimeras, one of which had the cytoplasmic domain of TfR2 and the remaining portion of TfR1 and the other with the cytoplasmic and transmembrane domain of TfR1 joined to the ectodomain of TfR2. Similar to TfR2, the levels of the chimera containing only the cytoplasmic domain of TfR2 increased in a time-and dose-dependent manner after the addition of holo-Tf to the medium. The half-life of the chimera increased 2.7-fold in cells exposed to holo-Tf like the endogenous TfR2 in HepG2 cells. Like TfR2 and unlike TfR1, the levels of the chimera did not respond to intracellular iron content. These results suggest that although holo-Tf binding to the ectodomain is necessary, the cytoplasmic domain of TfR2 is largely responsible for its stabilization by holo-Tf.

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“…These include the identification of the iron transporters divalent metal transporter 1 (DMT1) and ferroportin (Fpn), a novel transferrin receptor 2 (TFR2), hemojuvelin (Hjv), and the iron regulatory peptide hepcidin. [5][6][7][8][9][10][11] All of these are expressed in liver, and mutations in the latter four are associated with rare forms of iron overload. 10,[12][13][14][15] As the liver is important in the regulation of iron metabolism under normal circumstances, it is reasonable to surmise that hemosiderosis may result from dysregulated expression of one or more of iron-related proteins in cirrhosis.…”

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confidence: 99%

Altered expression of iron regulatory genes in cirrhotic human livers: clues to the cause of hemosiderosis?

Bergmann

Mathahs

Broadhurst

et al. 2008

Laboratory Investigation

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Hepatic iron deposition unrelated to hereditary hemochromatosis occurs commonly in cirrhosis but the pathogenesis of this condition is unknown. The aim of this study was to compare the expression of genes involved in the regulation of iron metabolism in cirrhotic (n ¼ 22) and control human livers (n ¼ 5). Transcripts were quantitated by real-time RT-PCR and protein levels were assessed by western blot. Hepatic iron concentrations (HICs) were measured by a spectrophotometric method. Levels of hepcidin mRNA did not differ between controls and cirrhotic livers; there was a highly significant correlation between hepcidin transcript levels and HIC in the latter group. Ferroportin, divalent metal transporter-1 (DMT1), and ferritin heavy chain mRNA levels were significantly higher in cirrhotic human livers than in controls (P ¼ 0.007, 0.039, and 0.025, respectively). By western blot, ferroportin and DMT1 levels were generally diminished in the cirrhotic livers compared to controls; neither correlated with HIC. In contrast, the abundance of ferritin increased with increasing HIC in the cirrhotic livers, whereas transferrin receptor decreased, indicating physiologically appropriate regulation. In conclusion, hepcidin expression appears to be appropriately responsive to iron status in cirrhosis. However, there are complex alterations in DMT1 and ferroportin expression in cirrhotic liver, including decreases in ferroportin and DMT1 at the protein level that may play a role in aberrant regulation of iron metabolism in cirrhosis.

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Molecular Cloning of Transferrin Receptor 2

Cited by 557 publications

References 30 publications

Deregulation of iron homeostasis and cold-preservation injury to rat liver stored in University of Wisconsin solution

Deregulation of iron homeostasis and cold-preservation injury to rat liver stored in University of Wisconsin solution

The Cytoplasmic Domain of Transferrin Receptor 2 Dictates Its Stability and Response to Holo-transferrin in Hep3B Cells

Altered expression of iron regulatory genes in cirrhotic human livers: clues to the cause of hemosiderosis?

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