Potent Transforming Activity of the G13 α Subunit Defines a Novel Family of Oncogenes
Potent Transforming Activity of the G13 α Subunit Defines a Novel Family of Oncogenes
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G13 α 亚基的有效转化活性定义了一个新的癌基因家族
DOI：
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发表时间：
1994
期刊：
影响因子：
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通讯作者：
J. Gutkind
中科院分区：
文献类型：
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作者：
N. Xu;T. Voyno;J. Gutkind
摘要某些内分泌肿瘤中Gs和Gi2 α亚基基因中GTPase抑制突变的发现表明异三聚体G蛋白可能有助于肿瘤形成。NIH 3T3鼠成纤维细胞中αs或αi2的这些活化形式的表达诱导细胞生长的某些改变，但转化较弱。另一个G蛋白家族的α亚基Gq的突变激活形式在NIH 3T3细胞中是完全致癌的，尽管效力非常低。相反，我们最近发现一种新的G蛋白G12的α亚基的过度表达本身就具有转化作用，α12的激活突变体表现为已知最强的癌基因之一。在这项研究中，我们探索了Gα12家族的另一个成员Gα13是否具有转化潜力。我们的数据表明，Gα13可以作为一个有效的显性作用癌基因。这些发现有力地表明，G蛋白的G12家族代表了一类新的癌基因。
Abstract The finding of GTPase inhibiting mutations in genes for α subunits of Gs and Gi2 in certain endocrine tumors suggests that heterotrimeric G proteins might contribute to neoplasia. Expression of these activated forms of αs or αi2 in NIH 3T3 murine fibroblasts induces certain alterations in cell growth, but is weakly transforming. Mutationally activated forms of the α subunit of another G protein family, Gq are fully oncogenic in NIH 3T3 cells, although with a very low potency. In contrast, we have recently shown that overexpression of the α subunit of a novel G protein, G12, is itself transforming, and an activated mutant of α12 behaves as one of the most potent oncogenes known. In this study, we have explored whether another member of the Gα12 family, Gα13, harbors transforming potential. Our data demonstrate that Gα13 can behave as a potent dominant acting oncogene. These findings strongly suggest that the G12 family of G proteins represents a novel class of oncogenes.