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人类趋化因子受体CXCR1的一个同源物在小鼠中表达。

A homolog of the human chemokine receptor CXCR1 is expressed in the mouse.

作者信息

Moepps Barbara, Nuesseler Elke, Braun Mike, Gierschik Peter

机构信息

Department of Pharmacology and Toxicology, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany.

出版信息

Mol Immunol. 2006 Mar;43(7):897-914. doi: 10.1016/j.molimm.2005.06.043. Epub 2005 Aug 9.

Abstract

Two distinct genes are present in the human genome encoding receptors for human interleukin-8 (hCXCL8), referred to as hCXCR1 and hCXCR2. While it seems clear that orthologous genes are present in the genomes of several mammals, the existence of a gene encoding an ortholog of hCXCR1 in the mouse has thus far been controversial. We have isolated a cDNA that is highly similar to the cDNAs of hCXCR1 and hCXCR2, but is clearly distinct from the cDNA encoding mouse CXCR2 (mCXCR2). The encoded protein, designated mouse CXCR1-like (mCXCR1-like), shares 64, 57, 57, and 89% identical amino acids with hCXCR1, hCXCR2, mCXCR2, and rCXCR1-like, respectively. The gene encoding mCXCR1-like was mapped to mouse chromosome 1 and its genomic organization was determined to be very similar to the organization of the gene encoding hCXCR1. Like hCXCR1, mCXCR1-like was found to be expressed at the mRNA level in neutrophils. In addition, mRNA encoding mCXCR1-like was detected in liver, kidney, and spleen. In spleen, mCXCR1-like transcripts were predominantly found in CD4+ T cells. In liver, mCXCR1-like transcripts were identified in residual CD3+ T cells and macrophages, suggesting that mCXCR1-like may regulate inflammatory and immunological processes in the liver. When expressed as a recombinant protein, mCXCR1-like was not activated by a large panel of known CXC chemokines of human and murine origin. These findings suggest that a homolog or ortholog of hCXCR1 is expressed in the mouse to be activated by a hitherto unknown CXC chemokine of the mouse.

摘要

人类基因组中存在两个不同的基因,它们编码人白细胞介素-8(hCXCL8)的受体,分别称为hCXCR1和hCXCR2。虽然很明显几种哺乳动物的基因组中存在直系同源基因,但迄今为止,小鼠中编码hCXCR1直系同源物的基因的存在一直存在争议。我们分离出了一种与hCXCR1和hCXCR2的cDNA高度相似,但与编码小鼠CXCR2(mCXCR2)的cDNA明显不同的cDNA。所编码的蛋白质命名为小鼠CXCR1样蛋白(mCXCR1样蛋白),与hCXCR1、hCXCR2、mCXCR2和rCXCR1样蛋白分别有64%、57%、57%和89%的相同氨基酸。编码mCXCR1样蛋白的基因被定位到小鼠1号染色体上,其基因组结构被确定与编码hCXCR1的基因结构非常相似。与hCXCR1一样,发现mCXCR1样蛋白在中性粒细胞的mRNA水平表达。此外,在肝脏、肾脏和脾脏中检测到了编码mCXCR1样蛋白的mRNA。在脾脏中,mCXCR1样转录本主要存在于CD4+T细胞中。在肝脏中,在残余的CD3+T细胞和巨噬细胞中鉴定出了mCXCR1样转录本,这表明mCXCR1样蛋白可能调节肝脏中的炎症和免疫过程。当作为重组蛋白表达时,mCXCR1样蛋白不会被大量已知的人和鼠源CXC趋化因子激活。这些发现表明,hCXCR1的同源物或直系同源物在小鼠中表达,可被一种迄今未知的小鼠CXC趋化因子激活。

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