PMID- 15521925
OWN - NLM
STAT- MEDLINE
DCOM- 20041217
LR  - 20111117
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 127
IP  - 4
DP  - 2004 Nov
TI  - Analyses for binding of the transferrin family of proteins to the transferrin 
      receptor 2.
PG  - 464-73
AB  - Transferrin receptor 2 alpha (TfR2 alpha), 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 alpha 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 
      alpha using human transferrin receptor 1 (TfR1) and TfR2 alpha-stably transfected 
      and expressing cells and flow-cytometric techniques. We showed that human TfR2 
      alpha interacted with both human and bovine Tf, whereas human TfR1 interacted 
      only with human Tf. Neither human TfR1 nor TfR2 alpha interacted with either 
      lactoferrin or melanotransferrin. In addition, by creating point mutations in 
      human TfR2 alpha, the RGD sequence in the extracellular domain of TfR2 alpha was 
      shown to be crucial for Tf-binding. Furthermore, we demonstrated that mutated 
      TfR2 alpha (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 alpha 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.
FAU - Kawabata, Hiroshi
AU  - Kawabata H
AD  - Division of Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, 
      USA. hkawabat@kanazawa-med.ac.jp
FAU - Tong, Xiangjun
AU  - Tong X
FAU - Kawanami, Takafumi
AU  - Kawanami T
FAU - Wano, Yuji
AU  - Wano Y
FAU - Hirose, Yuko
AU  - Hirose Y
FAU - Sugai, Susumu
AU  - Sugai S
FAU - Koeffler, H Phillip
AU  - Koeffler HP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Receptors, Transferrin)
RN  - 0 (TFR2 protein, human)
RN  - 0 (Transferrin)
SB  - IM
MH  - Biotinylation
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Flow Cytometry
MH  - Humans
MH  - Mutation/genetics
MH  - Receptors, Transferrin/genetics/*metabolism
MH  - Transferrin/genetics/*metabolism
EDAT- 2004/11/04 09:00
MHDA- 2004/12/18 09:00
CRDT- 2004/11/04 09:00
PHST- 2004/11/04 09:00 [pubmed]
PHST- 2004/12/18 09:00 [medline]
PHST- 2004/11/04 09:00 [entrez]
AID - BJH5224 [pii]
AID - 10.1111/j.1365-2141.2004.05224.x [doi]
PST - ppublish
SO  - Br J Haematol. 2004 Nov;127(4):464-73. doi: 10.1111/j.1365-2141.2004.05224.x.