Cloning and functional expression of mCCR2, a murine receptor for the C-C chemokines JE and FIC
Cloning and functional expression of mCCR2, a murine receptor for the C-C chemokines JE and FIC
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DOI：
10.1074/jbc.271.20.11603
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发表时间：
1996-05-17
影响因子：
4.8
通讯作者：
Bravo, R
中科院分区：
文献类型：
--
作者：
Kurihara, T;Bravo, R
C-C趋化因子人单核细胞趋化蛋白-1和-3（MCP-1和MCP-3）以及小鼠JE和FIC是单核细胞的有效激活剂。已经从人单核细胞系中克隆了MCP-1和MCP-3的几种受体，其中一种受体CCR 2B结合MCP-1和MCP-3。到目前为止，还没有关于JE或FIC的鼠受体的报道。我们从小鼠单核细胞系WEHI 265.1中克隆了一种新的小鼠C-C趋化因子受体，命名为小鼠CCR 2（mCCR 2）。预测的mCCR 2的373个氨基酸序列显示与CCR 2B的最高同一性（80%）。当在人胚肾293细胞中稳定表达时，mCCR 2以高亲和力特异性结合I-125-JE。FIC在竞争I-125-JE与mCCR 2表达细胞的结合方面不如JE有效，而其他三种小鼠趋化因子MIP-1 α、C10和N51/KC不竞争。在诱导的腹腔巨噬细胞以及几种小鼠器官中检测到mccr 2 mRNA表达。mCCR 2的克隆为研究单核细胞/巨噬细胞对JE和FIC的反应，鉴定其作用的其他靶点，并可能研究小鼠中CCR 2功能的模型提供了重要工具。
The C-C chemokines human monocyte chemoattractant protein-1 and -3 (MCP-1 and MCP-3) and mouse JE and FIC are potent activators of monocytes. Several receptors for MCP-1 and MCP-3 have been cloned from human monocytic cell lines, and one of these receptors, CCR2B, binds both MCP-1 and MCP-3. Thus far, no murine receptors for JE or FIC have been reported. We have cloned a novel murine C-C chemokine receptor, designated mouse CCR2 (mCCR2), from the mouse monocyte cell line WEHI265.1. The predicted 373-amino acid sequence of mCCR2 shows highest identity (80%) with CCR2B. When stably expressed in human embryonic kidney 293 cells, mCCR2 specifically bound I-125-JE with high affinity. FIC was less potent than JE in competing I-125-JE binding to mCCR2-expressing cells, while three other mouse chemokines, MIP-1 alpha, C10, and N51/KC, did not compete. mccr2 mRNA expression was detected in elicited peritoneal macrophages as well as in several mouse organs. The cloning of mCCR2 provides an important tool to investigate monocyte/macrophage responses to JE and FIC, to identify other targets for their action, and potentially to study models of CCR2 function in the mouse.