Different subcellular localizations for the related interferon-induced GTPases, MuGBP-1 and MuGBP-2: implications for different functions?
Different subcellular localizations for the related interferon-induced GTPases, MuGBP-1 and MuGBP-2: implications for different functions?
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DOI：
10.1089/10799900050198435
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发表时间：
2000-11
期刊：
影响因子：
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通讯作者：
D. Vestal;Victoria Y. Gorbacheva;Ganes C. Sen
中科院分区：
文献类型：
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作者：
D. Vestal;Victoria Y. Gorbacheva;Ganes C. Sen
鸟苷酸结合蛋白（GBP）是由I型和II型干扰素（IFN）诱导的65-67-kDa蛋白质家族。GTP酶的GBP家族的成员是最丰富的IFN-γ诱导的蛋白质之一。GBP含有一个不寻常的GTP结合位点，这与GBP将GTP水解为GDP和GMP一致。此外，八种已知的GBP中的六种具有用于添加异戊二烯基脂质的羧基末端CaaX基序。然而，尽管它们丰富，但对GBP的生物学功能或细胞位置知之甚少。我们在这里报告的研究，本地化的一个新发现的小鼠GBP（MuGBP-2）和它的密切相关的家庭成员，MuGBP-1。在IFN处理的巨噬细胞和成纤维细胞中，MuGBP-2被发现在整个细胞质中的颗粒分布和定位于异质尺寸的囊泡群体。MuGBP-2在囊泡中的定位依赖于其异戊二烯化。尽管具有高度的序列同一性和存在相同的CaaX序列，MuGBP-1具有非常均匀的细胞质分布，不能定位于细胞内囊泡。这两个密切相关的家族成员的不同细胞内分布表明了不同的功能。
The guanylate-binding proteins (GBPs) are a family of 65-67-kDa proteins induced by both type I and type II interferons (IFN). Members of the GBP family of GTPases are among the most abundant IFN-gamma-induced proteins. GBPs contain an unusual GTP binding site, which is consistent with GBP hydrolysis of GTP to both GDP and GMP. In addition, six of the eight known GBPs have a carboxy-terminal CaaX motif for the addition of isoprenyl lipids. Despite their abundance, however, little is known about the biologic function or cellular location of GBPs. We report here on studies to localize both a newly identified murine GBP (MuGBP-2) and its closely related family member, MuGBP-1. In both IFN-treated macrophages and fibroblasts, MuGBP-2 is found in both a granular distribution throughout the cytoplasm and localized to vesicle populations of heterogeneous sizes. The localization of MuGBP-2 to vesicles is dependent on its isoprenylation. Despite a high degree of sequence identity and the presence of an identical CaaX sequence, MuGBP-1 has a very homogeneous cytoplasmic distribution and fails to localize to intracellular vesicles. The different intracellular distribution of these two closely related family members suggests differential function(s).