The interferon (IFN)-induced GTPase, mGBP-2 -: Role in IFN-γ-induced murine fibroblast proliferation
The interferon (IFN)-induced GTPase, mGBP-2 -: Role in IFN-γ-induced murine fibroblast proliferation
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DOI：
10.1074/jbc.m110542200
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发表时间：
2002-02-22
影响因子：
4.8
通讯作者：
Vestal, DJ
中科院分区：
文献类型：
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作者：
Gorbacheva, VY;Lindner, D;Vestal, DJ
mGBP-2是干扰素（IFN）诱导的鸟苷酸结合蛋白家族的一员，为了研究其功能，我们生成了组成性表达mGBP-2的NIH 3T3成纤维细胞。mGBP-2诱导了更快的生长速度，最高表达的克隆显示出大约50%的倍增时间减少。表达mgbp -2的细胞也生长到更高的密度，并表现出部分失去接触生长抑制，这在融合后培养中形成了灶。此外，表达mgbp -2的细胞对血清源性生长因子的依赖性降低。然而，它们并没有失去依赖锚地生长的需求。最后，表达mGBP-2的NTH 3T3细胞在胸腺小鼠体内形成肿瘤。携带减少GTP结合的点突变（S52N）的mGBP-2蛋白在与野生型相同水平表达时不能产生这些表型。另外的发现是，ifn - γ处理NIH 3T3细胞导致增殖增加，类似于在缺乏其他ifn诱导蛋白的情况下观察到的mGBP-2，这表明mGBP-2可能确实对这些生长变化很重要。
To investigate the function of mGBP-2, a member of the interferon (IFN)-induced guanylate-binding protein family of GTPases, NIH 3T3 fibroblasts were generated that constitutively expressed mGBP-2. mGBP-2 induced a faster growth rate, with the highest expressing clones showing approximately a 50% reduction in doubling time. mGBP-2-expressing cells also grew to higher density and exhibited partial loss of contact growth inhibition, as evidenced by the formation of foci in post-confluent cultures. In addition, mGBP-2-expressing cells showed decreased dependence on serum-derived growth factors. However, they did not lose the requirement for anchorage-dependent growth. Finally, NTH 3T3 cells expressing mGBP-2 formed tumors in athymic mice. An mGBP-2 protein carrying a point mutation (S52N) that reduced GTP binding failed to produce these phenotypes when expressed at the same levels as wild type. The additional finding that IFN-gamma treatment of NIH 3T3 cells resulted in an increase in proliferation similar to that observed for mGBP-2 in the absence of other IFN-induced proteins suggests that mGBP-2 may indeed be important for these growth changes.