論文

査読有り
2017年2月

Role of CXC chemokine receptor type 4 as a lactoferrin receptor

BIOCHEMISTRY AND CELL BIOLOGY
  • Yoshiharu Takayama
  • ,
  • Reiji Aoki
  • ,
  • Ryo Uchida
  • ,
  • Atsushi Tajima
  • ,
  • Ayako Aoki-Yoshida

95
1
開始ページ
57
終了ページ
63
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1139/bcb-2016-0039
出版者・発行元
CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS

Lactoferrin exerts its biological activities by interacting with receptors on target cells, including LDL receptor-related protein-1 (LRP-1/CD91), intelectin-1 (omentin-1), and Toll-like receptor 4 (TLR4). However, the effects mediated by these receptors are not sufficient to fully explain the many functions of lactoferrin. C-X-C-motif cytokine receptor 4 (CXCR4) is a ubiquitously expressed G-protein coupled receptor for stromal cell-derived factor-1 (SDF-1/CXCL12). Lactoferrin was found to be as capable as SDF-1 in blocking infection by an HIV variant that uses CXCR4 as a co-receptor (X4-tropic HIV), suggesting that lactoferrin interacts with CXCR4. We addressed whether CXCR4 acts as a lactoferrin receptor using HaCaT human keratinocytes and Caco-2 human intestinal cells. We found that bovine lactoferrin interacted with CXCR4-containing lipoparticles, and that this interaction was not antagonized by SDF-1. In addition, activation of Akt in response to lactoferrin was abrogated by AMD3100, a small molecule inhibitor of CXCR4, or by a CXCR4-neutralizing antibody, suggesting that CXCR4 functions as a lactoferrin receptor able to mediate activation of the PI3K-Akt signaling pathway. Lactoferrin stimulation mimicked many aspects of SDF-1-induced CXCR4 activity, including receptor dimerization, tyrosine phosphorylation, and ubiquitination. Cycloheximide chase assays indicated that turnover of CXCR4 was accelerated in response to lactoferrin. These results indicate that CXCR4 is a potent lactoferrin receptor that mediates lactoferrin-induced activation of Akt signaling.

Web of Science ® 被引用回数 : 7

リンク情報
DOI
https://doi.org/10.1139/bcb-2016-0039
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28075616
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000395528400010&DestApp=WOS_CPL