Neote K, DiGregorio D, Mak J Y, Horuk R, Schall T J
Department of Immunology, Genentech, Incorporated, South San Francisco, California 94080.
Cell. 1993 Feb 12;72(3):415-25. doi: 10.1016/0092-8674(93)90118-a.
The immunoregulatory proteins C-C chemokines are potent chemoattractants of lymphocytes and monocytes, as well as activators and attractants of eosinophils and basophils. We have isolated a cDNA that encodes a seven transmembrane-spanning receptor, with homology to other chemoattractant receptors, that encodes a protein designated C-C CKR-1 that acts as a receptor for the C-C chemokines. Human and murine macrophage inflammatory protein 1 alpha (MIP-1 alpha), human human monocyte chemotactic protein 1 (MCP-1), and RANTES all bind to the C-C CKR-1 with varying affinities. Chemokine binding affinity does not predict how well the ligand will transmit a signal through the receptor: RANTES and human MIP-1 alpha induce a similar intracellular calcium flux while binding with disparate affinities, while MCP-1 and human MIP-1 beta induce calcium mobilization only at high concentrations. Finally, C-C chemokines were shown to bind a C-C CKR-1-related gene product encoded by cytomegalovirus, suggesting a role for C-C chemokines in viral immunity.
免疫调节蛋白C-C趋化因子是淋巴细胞和单核细胞的有效趋化剂，也是嗜酸性粒细胞和嗜碱性粒细胞的激活剂和趋化剂。我们分离出了一个编码七次跨膜受体的cDNA，它与其他趋化因子受体具有同源性，该受体编码一种名为C-C CKR-1的蛋白，它作为C-C趋化因子的受体发挥作用。人及小鼠巨噬细胞炎性蛋白1α（MIP-1α）、人单核细胞趋化蛋白1（MCP-1）和调节激活正常T细胞表达和分泌因子（RANTES）均以不同亲和力与C-C CKR-1结合。趋化因子结合亲和力并不能预测配体通过受体传递信号的效果：RANTES和人MIP-1α诱导相似的细胞内钙流，但其结合亲和力不同，而MCP-1和人MIP-1β仅在高浓度时诱导钙动员。最后，研究表明C-C趋化因子能结合巨细胞病毒编码的一种与C-C CKR-1相关的基因产物，提示C-C趋化因子在病毒免疫中发挥作用。
