Combadiere C, Salzwedel K, Smith E D, Tiffany H L, Berger E A, Murphy P M
Laboratory of Host Defenses, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Biol Chem. 1998 Sep 11;273(37):23799-804. doi: 10.1074/jbc.273.37.23799.
Fractalkine is a multimodular human leukocyte chemoattractant protein and a member of the chemokine superfamily. Unlike other human chemokines, the chemokine domain of fractalkine has three amino acids between two conserved cysteines, referred to as the CX3C motif. Both plasma membrane-associated and shed forms of fractalkine have been identified. Here, we show that the recombinant 76-amino acid chemokine domain of fractalkine is a potent and highly specific chemotactic agonist at a human orphan receptor previously named V28 or alternatively CMKBRL1 (chemokine beta receptor-like 1), which was shown previously to be expressed in neutrophils, monocytes, T lymphocytes, and several solid organs, including brain. CMKBRL1/V28 also functioned with CD4 as a coreceptor for the envelope protein from a primary isolate of HIV-1 in a cell-cell fusion assay, and fusion was potently and specifically inhibited by fractalkine. Thus CMKBRL1/V28 is a specific receptor for fractalkine, and we propose to rename it CX3CR1 (CX3C chemokine receptor 1), according to an accepted nomenclature system.
fractalkine是一种多模块人类白细胞趋化蛋白，属于趋化因子超家族成员。与其他人类趋化因子不同，fractalkine的趋化因子结构域在两个保守的半胱氨酸之间有三个氨基酸，称为CX3C基序。已鉴定出fractalkine的细胞膜相关形式和可溶性形式。在此，我们表明，fractalkine重组的76个氨基酸的趋化因子结构域是一种强效且高度特异性的趋化激动剂，作用于一种先前称为V28或CMKBRL1（趋化因子β受体样1）的人类孤儿受体，先前已证明该受体在中性粒细胞、单核细胞、T淋巴细胞以及包括脑在内的多个实体器官中表达。在细胞 - 细胞融合试验中，CMKBRL1/V28还与CD4一起作为来自HIV - 1原代分离株包膜蛋白的共受体发挥作用，并且fractalkine可有效且特异性地抑制融合。因此，CMKBRL1/V28是fractalkine的特异性受体，根据公认的命名系统，我们建议将其重新命名为CX3CR1（CX3C趋化因子受体1）。
