Importance of the amino terminus of the interleukin-8 receptor in ligand interactions.
Importance of the amino terminus of the interleukin-8 receptor in ligand interactions.
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DOI：
10.1016/s0021-9258(18)53174-4
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发表时间：
1993-04
期刊：
影响因子：
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通讯作者：
R. Gayle;P. Sleath;S. Srinivason;C. Birks;K. Weerawarna;D. Cerretti;C. Kozlosky;N. Nelson;T. Vanden Bos;M. Beckmann
中科院分区：
文献类型：
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作者：
R. Gayle;P. Sleath;S. Srinivason;C. Birks;K. Weerawarna;D. Cerretti;C. Kozlosky;N. Nelson;T. Vanden Bos;M. Beckmann
白细胞介素-8（IL-8）和生长调节基因/黑色素瘤生长刺激活性（GRO/MGSA）是参与某些细胞类型的趋化反应的小多肽分子。已经描述了两种与IL-8相互作用的受体，称为1型和2型。IL-8以高亲和力结合两种受体，而GRO/MGSA和嗜中性粒细胞活化肽-2仅表现出高度结合2型受体。这两种形式的IL-8受体是视紫红质七螺旋跨膜超家族的成员，并且具有高度的整体同源性，尽管氨基末端非常不同。利用保守的限制性内切酶位点，构建了一系列介于1型和2型受体之间的嵌合IL-8受体分子，并转染人293肾上皮细胞。这些嵌合分子改变了受体呈递给配体的区域。测定嵌合受体结合IL-8的能力，以及IL-8和GRO/MGSA抑制放射性标记的IL-8结合的能力。发现IL-8受体的氨基末端对于GRO/MGSA和IL-8的差异结合是重要的。此外，还构建了一系列肽段，以进一步研究IL-8受体的哪些残基与IL-8相互作用。这些肽还鉴定了IL-8受体的氨基末端序列在与IL-8相互作用中是重要的。
Interleukin-8 (IL-8) and growth regulatory gene/melanoma growth stimulatory activity (GRO/MGSA) are small polypeptide molecules involved in the chemotactic response of certain cell types. Two receptors have been described which interact with IL-8, designated type 1 and type 2. IL-8 binds with high affinity to both receptors, whereas GRO/MGSA and neutrophil-activating peptide-2 demonstrate a high degree of binding only to the type 2 receptor. The two forms of IL-8 receptor are members of the rhodopsin seven-helix membrane-spanning superfamily, and share a high degree of overall homology, although the amino termini are very divergent. By using conserved restriction enzyme sites, a series of chimeric IL-8 receptor molecules were constructed between the type 1 and type 2 receptors and transfected into human 293 kidney epithelial cells. These chimeric molecules altered regions of the receptor presented to the ligand. The ability of the chimeric receptors to bind IL-8 was determined, as well as the ability of IL-8 and GRO/MGSA to inhibit radiolabeled IL-8 binding. The amino terminus of the IL-8 receptors was found to be important for differential binding of GRO/MGSA and IL-8. In addition, a series of peptides was also constructed to further investigate which residues of IL-8 receptor interact with IL-8. These peptides also identified the amino-terminal sequence of the IL-8 receptors as being important in interacting with IL-8.