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Heterotypic interactions between transferrin receptor and transferrin receptor 2

Vogt, Todd M. and Blackwell, Aaron D. and Giannetti, Anthony M. and Bjorkman, Pamela J. and Enns, Caroline A. (2003) Heterotypic interactions between transferrin receptor and transferrin receptor 2. Blood, 101 (5). pp. 2008-2014. ISSN 0006-4971. doi:10.1182/blood-2002-09-2742.

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Cellular iron uptake in most tissues occurs via endocytosis of diferric transferrin (Tf) bound to the transferrin receptor (TfR). Recently, a second transferrin receptor, transferrin receptor 2 (TfR2), has been identified and shown to play a critical role in iron metabolism. TfR2 is capable of Tf-mediated iron uptake and mutations in this gene result in a rare form of hereditary hemochromatosis unrelated to the hereditary hemochromatosis protein, HFE. Unlike TfR, TfR2 expression is not controlled by cellular iron concentrations and little information is currently available regarding the role of TfR2 in cellular iron homeostasis. To investigate the relationship between TfR and TfR2, we performed a series of in vivo and in vitro experiments using antibodies generated to each receptor. Western blots demonstrate that TfR2 protein is expressed strongest in erythroid/myeloid cell lines. Metabolic labeling studies indicate that TfR2 protein levels are approximately 20-fold lower than TfR in these cells. TfR and TfR2 have similar cellular localizations in K562 cells and coimmunoprecipitate to only a very limited extent. Western analysis of the receptors under nonreducing conditions reveals that they can form heterodimers.

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Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 2003 The American Society of Hematology. Submitted September 9, 2002. Accepted October 16, 2002. Prepublished online as Blood First Edition Paper, October 24, 2002; DOI 10.1182/blood-2002-09-2742. We would like to thank Dr Tim McGraw, Cornell Medical College for the TRVb and the TRVb1 cell lines; Drs Kawabata and Koeffler for the human TfR2 plasmid; Anthony P. West for the TfR2 used in the immunizations; Thomas O'Hare and Greg Wiens for critical comments on the manuscript; and Aeisha D. Robb and Marianne Wessling-Resnick for insightful discussions. Supported by National Institutes of Health grant DK 40608 (C.A.E.) and Howard Hughes Medical Center (P.J.B.). The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked “advertisement” in accordance with 18 U.S.C. section 1734.
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NIHDK 40608
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:5
Record Number:CaltechAUTHORS:20170327-133908801
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Official Citation:Vogt, T. M., Blackwell, A. D., Giannetti, A. M., Bjorkman, P. J., & Enns, C. A. (2003). Heterotypic interactions between transferrin receptor and transferrin receptor 2. Blood, 101(5), 2008-2014. Accessed March 27, 2017.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:75424
Deposited By: Tony Diaz
Deposited On:27 Mar 2017 20:45
Last Modified:15 Nov 2021 16:33

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