Murine GBP-5, a new member of the murine guanylate-binding protein family, is coordinately regulated with other GBPs in vivo and in vitro
Murine GBP-5, a new member of the murine guanylate-binding protein family, is coordinately regulated with other GBPs in vivo and in vitro
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DOI：
10.1089/107999002760274926
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发表时间：
2002-08-01
影响因子：
2.3
通讯作者：
Smith, JB
中科院分区：
文献类型：
--
作者：
Nguyen, TT;Hu, Y;Smith, JB
一个新的干扰素（IFN）诱导的鸟苷酸结合蛋白（GBP）家族的小鼠成员被克隆在寻找糖皮质激素减弱的反应基因诱导肺内毒素血症。全长MuGBP-5 cDNA编码590个氨基酸残基的蛋白质，其GTP结合基序与人GBP-1（HuGBP-1）中的GTP结合基序相同，并且在C-末端具有相似的异戊二烯化序列。还鉴定了缺少第二GTP结合基序并且在C-末端不同的MuGBP-5的可变剪接形式。MuGBP-5基因位于3号染色体上，靠近MuGBP-3和MuGBP-2，具有与其他GBP基因相似的基因组结构。为了便于评估GBP家族信息表达，我们构建了MuGBP-1、MuGBP-2、MuGBP-3、MuGBP-4/Mag-2（巨噬细胞活化基因-2）和MuGBP-5的RNA酶保护测定探针，并在Swiss韦伯斯特、BALB/c和C57 BL/6小鼠中验证了它们的用途。在BALB/c小鼠中，所有五种MuGBP在内毒素血症期间在多个器官中诱导，并且在不同组织中均具有相似的表达模式。在RAW 264.7和Swiss 3 T3细胞中，MuGBP对IFN-γ、脂多糖（LPS）、白细胞介素-1 β（IL-1 β）和肿瘤坏死因子-α（TNF-α）的反应模式也相似，但数量差异较小。MuGBP的协调表达表明它们具有共同的调节机制。
A new murine member of the interferon (IFN)-inducible guanylate-binding protein (GBP) family was cloned in a search for glucocorticoid-attenuated response genes induced in the lung during endotoxemia. The full-length MuGBP-5 cDNA encodes a 590 amino acid residue protein with GTP binding motifs identical to those in human GBP-1(HuGBP-1) and a similar isoprenylation sequence at the C-terminus. An alternatively spliced form of MuGBP-5 that lacks the second GTP binding motif and differs at the C-terminus was also identified. The MuGBP-5 gene is located on chromosome 3, near MuGBP-3 and MuGBP-2, and has a genomic organization similar to other GBP genes. To facilitate the evaluation of GBP family message expression, we constructed RNase protection assay probes for MuGBP-1, MuGBP-2, MuGBP-3, MuGBP-4/Mag-2 (macrophage activation gene-2), and MuGBP-5 and validated their use in Swiss Webster, BALB/c, and C57BL/6 mice. In BALB/c mice, all five MuGBPs were induced in multiple organs during endotoxemia, and all had a similar pattern of expression in different tissues. With minor quantitative differences, the MuGBPs also had similar patterns of response to IFN-gamma, lipopolysaccharide (LPS), interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha) in RAW 264.7 and Swiss 3T3 cells. The coordinate expression of the MuGBPs suggests that they share common mechanisms of regulation.