Raport C J, Gosling J, Schweickart V L, Gray P W, Charo I F
ICOS Corporation, Bothell, Washington 98021, USA.
J Biol Chem. 1996 Jul 19;271(29):17161-6. doi: 10.1074/jbc.271.29.17161.
Chemokines affect leukocyte chemotactic and activation activities through specific G protein-coupled receptors. In an effort to map the closely linked CC chemokine receptor genes, we identified a novel chemokine receptor encoded 18 kilobase pairs downstream of the monocyte chemoattractant protein-1 (MCP-1) receptor (CCR2) gene on human chromosome 3p21. The deduced amino acid sequence of this novel receptor, designated CCR5, is most similar to CCR2B, sharing 71% identical residues. Transfected cells expressing the receptor bind RANTES (regulated on activation normal T cell expressed), MIP-1beta, and MIP-1alpha with high affinity and generate inositol phosphates in response to these chemokines. This same combination of chemokines has recently been shown to potently inhibit human immunodeficiency virus replication in human peripheral blood leukocytes (Cocchi, F., DeVico, A. L., Garzino-Demo, A., Arya, S. K., Gallo, R. C., and Lusso, P.(1995) Science 270, 1811-1815). CCR5 is expressed in lymphoid organs such as thymus and spleen, as well as in peripheral blood leukocytes, including macrophages and T cells, and is the first example of a human chemokine receptor that signals in response to MIP-1beta.
趋化因子通过特定的G蛋白偶联受体影响白细胞的趋化和激活活性。为了定位紧密连锁的CC趋化因子受体基因，我们在人类3号染色体p21上单核细胞趋化蛋白-1（MCP-1）受体（CCR2）基因下游18千碱基对处鉴定出一个新的趋化因子受体。这个新受体被命名为CCR5，其推导的氨基酸序列与CCR2B最为相似，有71%的相同残基。表达该受体的转染细胞以高亲和力结合RANTES（活化正常T细胞表达上调因子）、MIP-1β和MIP-1α，并在这些趋化因子作用下产生肌醇磷酸。最近发现，同样的趋化因子组合能有效抑制人类免疫缺陷病毒在人外周血白细胞中的复制（科基，F.，德维科，A.L.，加尔齐诺-德莫，A.，阿亚，S.K.，加洛，R.C.，卢索，P.（1995年）《科学》270，1811 - 1815）。CCR5在诸如胸腺和脾脏等淋巴器官以及外周血白细胞（包括巨噬细胞和T细胞）中表达，并且是首个对MIP-1β产生信号应答的人类趋化因子受体实例。
