Interaction of human lactoferrin with cell adhesion molecules through RGD motif elucidated by lactoferrin-binding epitopes
Interaction of human lactoferrin with cell adhesion molecules through RGD motif elucidated by lactoferrin-binding epitopes
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DOI：
10.1074/jbc.m604974200
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发表时间：
2006-08-25
影响因子：
4.8
通讯作者：
Sugimura, Kazuhisa
中科院分区：
文献类型：
--
作者：
Sakamoto, Kotaro;Ito, Yuji;Sugimura, Kazuhisa
乳铁蛋白（LF）是一种分泌性铁结合蛋白，广泛分布于多核淋巴细胞次级颗粒和乳汁中。虽然它具有多种功能，例如抗微生物、免疫调节、抗病毒和抗肿瘤转移活性，但负责这些活性的受体尚未完全了解。本研究首先从T7噬菌体展示的六聚体随机肽库中筛选出人LF的结合表位。有趣的是，四种分离的肽中的两种具有代表性的细胞粘附基序Arg-Gly-Asp（RGD），这意味着人LF与具有RGD基序的蛋白质相互作用。我们发现，人LF结合到含有RGD的人细胞外基质蛋白，纤连蛋白和玻连蛋白。此外，人LF抑制细胞粘附这些基质蛋白的浓度依赖性的方式，但不依赖于RGD的细胞粘附分子，如层粘连蛋白或胶原蛋白。这些结果表明，人LF的功能是阻断细胞表面和粘附分子之间的各种相互作用。这可以解释LF的多功能性。
Lactoferrin (LF) is an iron-binding secretory protein, which is distributed in the secondary granules of polynuclear lymphocytes as well as in the milk produced by female mammals. Although it has multiple functions, for example antimicrobial, immunomodulatory, antiviral, and anti-tumor metastasis activities, the receptors responsible for these activities are not fully understood. In this study, the binding epitopes for human LF were first isolated from a hexameric random peptide library displayed on T7 phage. Interestingly, two of the four isolated peptides had a representative cell adhesion motif, Arg-Gly-Asp (RGD), implying that human LF interacts with proteins with the RGD motif. We found that human LF bound to the RGD-containing human extracellular matrix proteins, fibronectin and vitronectin. Furthermore, human LF inhibited cell adhesion to these matrix proteins in a concentration-dependent manner but not to the RGD-independent cell adhesion molecule like laminin or collagen. These results indicate that a function of human LF is to block the various interactions between the cell surface and adhesion molecules. This may explain the multifunctionality of LF.