論文 - 詳細
| RRC ID | 51915 |
|---|---|
| 著者 | Takayama Y, Aoki R, Uchida R, Tajima A, Aoki-Yoshida A. |
| タイトル | Role of CXC chemokine receptor type 4 as a lactoferrin receptor. |
| ジャーナル | Biochem Cell Biol |
| Abstract |
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. |
| 巻・号 | 95(1) |
| ページ | 57-63 |
| 公開日 | 2017-2-1 |
| DOI | 10.1139/bcb-2016-0039 |
| PMID | 28075616 |
| MeSH | Animals Blotting, Western Cattle Cells, Cultured Chemokine CXCL12 / metabolism Humans Immunoprecipitation Intestinal Mucosa / metabolism* Intestines / cytology Keratinocytes / cytology Keratinocytes / metabolism* Lactoferrin / metabolism* Phosphatidylinositol 3-Kinases / metabolism Proto-Oncogene Proteins c-akt / metabolism Receptors, CXCR4 / metabolism* Receptors, Cell Surface / metabolism* Ubiquitination |
| IF | 2.46 |
| 引用数 | 10 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | CACO-2(RCB0988) |