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前沿:鉴定出一种新型趋化因子受体,它可结合包括ELC、SLC和TECK在内的树突状细胞和T细胞活性趋化因子。

Cutting edge: identification of a novel chemokine receptor that binds dendritic cell- and T cell-active chemokines including ELC, SLC, and TECK.

作者信息

Gosling J, Dairaghi D J, Wang Y, Hanley M, Talbot D, Miao Z, Schall T J

机构信息

Divisions of Discovery Biology and Molecular Pharmacology, ChemoCentryx, San Carlos, CA 94070, USA.

出版信息

J Immunol. 2000 Mar 15;164(6):2851-6. doi: 10.4049/jimmunol.164.6.2851.

Abstract

Searching for new receptors of dendritic cell- and T cell-active chemokines, we used a combination of techniques to interrogate orphan chemokine receptors. We report here on human CCX CKR, previously represented only by noncontiguous expressed sequence tags homologous to bovine PPR1, a putative gustatory receptor. We employed a two-tiered process of ligand assignment, where immobilized chemokines constructed on stalks (stalkokines) were used as bait for adhesion of cells expressing CCX CKR. These cells adhered to stalkokines representing ELC, a chemokine previously thought to bind only CCR7. Adhesion was abolished in the presence of soluble ELC, SLC (CCR7 ligands), and TECK (a CCR9 ligand). Complete ligand profiles were further determined by radiolabeled ligand binding and competition with >80 chemokines. ELC, SLC, and TECK comprised high affinity ligands (IC50 <15 nM); lower affinity ligands include BLC and vMIP-II (IC50 <150 nM). With its high affinity for CC chemokines and homology to CC receptors, we provisionally designate this new receptor CCR10.

摘要

为寻找树突状细胞和T细胞活性趋化因子的新受体,我们运用了多种技术来研究孤儿趋化因子受体。我们在此报告人类CCX CKR,此前仅由与牛PPR1(一种假定的味觉受体)同源的不连续表达序列标签所代表。我们采用了两级配体鉴定过程,其中构建在茎上的固定化趋化因子(茎趋化因子)用作表达CCX CKR细胞黏附的诱饵。这些细胞黏附于代表ELC的茎趋化因子,ELC是一种先前认为仅与CCR7结合的趋化因子。在可溶性ELC、SLC(CCR7配体)和TECK(一种CCR9配体)存在的情况下,黏附被消除。通过放射性标记配体结合以及与80多种趋化因子的竞争进一步确定完整的配体谱。ELC、SLC和TECK构成高亲和力配体(IC50 <15 nM);较低亲和力的配体包括BLC和vMIP-II(IC50 <150 nM)。鉴于其对CC趋化因子的高亲和力以及与CC受体的同源性,我们暂时将这个新受体命名为CCR10。

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