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Analyses for binding of the transferrin family of proteins to the transferrin receptor 2
Author(s) -
Kawabata Hiroshi,
Tong Xiangjun,
Kawanami Takafumi,
Wano Yuji,
Hirose Yuko,
Sugai Susumu,
Phillip Koeffler H.
Publication year - 2004
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2004.05224.x
Subject(s) - transferrin receptor , transferrin , receptor , transfection , biology , microbiology and biotechnology , chemistry , biochemistry , gene
Summary Transferrin receptor 2 α (TfR2 α ), the major product of the TfR2 gene, is the second receptor for transferrin (Tf), which can mediate cellular iron uptake in vitro . Homozygous mutations of TfR2 cause haemochromatosis, suggesting that TfR2 α may not be a simple iron transporter, but a regulator of iron by identifying iron‐Tf. In this study, we analysed the ligand specificity of TfR2 α using human transferrin receptor 1 (TfR1) and TfR2 α ‐stably transfected and expressing cells and flow‐cytometric techniques. We showed that human TfR2 α interacted with both human and bovine Tf, whereas human TfR1 interacted only with human Tf. Neither human TfR1 nor TfR2 α interacted with either lactoferrin or melanotransferrin. In addition, by creating point mutations in human TfR2 α , the RGD sequence in the extracellular domain of TfR2 α was shown to be crucial for Tf‐binding. Furthermore, we demonstrated that mutated TfR2 α (Y250X), which has been reported in patients with hereditary haemochromatosis, also lost its ability to interact with both human and bovine Tf. Although human TfR1 and TfR2 α share an essential structure (RGD) for ligand‐binding, they have clearly different ligand specificities, which may be related to the differences in their roles in iron metabolism.