Cloning and functional expression of CC CKR5, a human monocyte CC chemokine receptor selective for MIP-1 alpha, MIP-1 beta, and RANTES

Cloning and functional expression of CC CKR5, a human monocyte CC chemokine receptor selective for MIP-1 alpha, MIP-1 beta, and RANTES
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DOI:
10.1002/jlb.60.1.147
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发表时间:
1996-07-01
影响因子:
5.5
通讯作者:
Murphy, PM
Murphy, PM
中科院分区:
医学3区
文献类型:
--
作者:
Combadiere, C;Ahuja, SK;Murphy, PM

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我们克隆了一种新的CC趋化因子受体(CC CKR)的人类cDNA,命名为CC CKR5,与其他CC CKR具有48-75%的氨基酸同源性,CC CKR5 mRNA在原代贴壁单核细胞中检测到,但在原代中性粒细胞或嗜酸性粒细胞中检测不到,巨噬细胞炎症蛋白-1 α (MIP-1 α), MIP-1 β和RANTES在转染的HEK 293细胞中测量钙流量时,都是CC CKR5的有效受体(EC(50) = 3-30 nM)。然而,相应的碘化趋化因子与表达受体的完整细胞的明显结合亲和力较低(IC50类似于100 nM)。这些数据表明CC CKR5是一种G(i)偶联受体,可能介导单核细胞对MIP-1 α、MIP-1 β和RANTES的反应。
We have cloned a human cDNA for a novel CC chemokine receptor (CC CKR) designated CC CKR5 that has 48-75% amino acid identity to other CC CKRs, CC CKR5 mRNA was detected constitutively in primary adherent monocytes but not in primary neutrophils or eosinophils, Macrophage inflammatory protein-1 alpha (MIP-1 alpha), MIP-1 beta, and RANTES were all potent agonists for CC CKR5 (EC(50) = 3-30 nM) when calcium flux was measured in transfected HEK 293 cells, yet the apparent binding affinities of the corresponding iodinated chemokines to intact cells expressing the receptor were low (IC50 similar to 100 nM). The calcium flux responses were completely blocked by treatment of transfected cells with pertussis toxin, These data suggest that CC CKR5 is a G(i)-coupled receptor that may mediate monocyte responses to MIP-1 alpha, MIP-1 beta, and RANTES.