Genomic organization and biological characterization of the novel human CC chemokine DC-CK-1/PARC/MIP-4/SCYA18
Genomic organization and biological characterization of the novel human CC chemokine DC-CK-1/PARC/MIP-4/SCYA18
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DOI：
10.1006/geno.1998.5635
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发表时间：
1999-03-15
期刊：
影响因子：
4.4
通讯作者：
McColl, SR
中科院分区：
文献类型：
--
作者：
Guan, P;Burghes, AHM;McColl, SR
趋化因子是一组趋化性分子，在体外和体内似乎调节白色血细胞的定向运动，因此可能在炎症和免疫中起重要作用。编码趋化因子的基因在物理上彼此接近地聚集。人类CC趋化因子基因的一个大簇位于17号染色体上，我们已经使用这个信息在定位克隆方法中鉴定该簇中的新趋化因子基因。我们构建了一个包含MIP-1 α（HGMW批准的符号SCYA 3）基因区域的YAC重叠群，并使用外显子捕获和序列分析来分离新的趋化因子基因。使用这种方法，基于其与MIP-1 α的同源性（核苷酸水平上的同源性为49.5%，预测的氨基酸水平上的同源性为59.6%），发现了编码趋化因子的基因MIP-4（HGMW批准的符号SCYA 18），其由分布在7.1kb上的三个外显子组成，与MIP-1 α基因相隔16 kb。MIP-4基因编码一个750 bp的mRNA，该mRNA在肺和巨噬细胞中表达，但在脑或肌肉中不表达。该mRNA编码一个89个氨基酸的蛋白，并包括一个预测的21个氨基酸的信号肽。将合成的MIP-4注射到小鼠的腹腔中导致CD 4（+）和CD 8（+）T淋巴细胞的积聚，但不是单核细胞或粒细胞。这些观察结果提供了关于CC趋化因子基因簇在人染色体17上的排列的新信息，并表明MIP-4基因产物在体内对CD 4（+）和CD 8（+）T淋巴细胞具有趋化性，因此可能与体液和细胞介导的免疫有关，（C）1999 Academic Press。
The chemokines are a group of chemotactic molecules that appear to regulate the directed movement of white blood cells in vitro and in vivo and may therefore play important roles in inflammation and immunity. The genes encoding the chemokines are clustered in close physical proximity to each other. A large cluster of human CC chemokine genes resides on chromosome 17, We have used this information in a positional cloning approach to identify novel chemokine genes within this cluster. We constructed a YAC contig encompassing the MIP-1 alpha (HGMW-approved symbol SCYA3) gene region and used exon trapping and sequence analysis to isolate novel chemokine genes. Using this approach, a gene encoding a chemokine named MIP-4, based on its homology with MIP-1 alpha (49.5% identity at the nucleotide level and 59.6% at the predicted amino acid level), was found. The MIP-4 gene (HGMW-approved symbol SCYA18) consists of three exons spread over 7.1 kb and is separated from the MIP-1 alpha gene by 16 kb. The MIP-4 gene encodes a 750-bp mRNA that is expressed in lung and macrophages but not in brain or muscle, The mRNA encodes an 89-amino-acid protein and includes a predicted signal peptide of 21 amino acids, Recombinant or synthetic MIP-4 induced calcium mobilization in naive and activated T lymphocyte subpopulations in vitro. Injection of synthetic MIP-4 into the peritoneal cavity of mice led to the accumulation of both CD4(+) and CD8(+) T lymphocytes, but not monocytes or granulocytes. These observations provide new information concerning the arrangement of the CC chemokine gene cluster on human chromosome 17 and indicate that the MIP-4 gene product is chemotactic in vivo for both CD4(+) and CD8(+) T lymphocytes and may therefore be implicated in both humoral and cell-mediated-immunity, (C) 1999 Academic Press.