Xu N, Voyno-Yasenetskaya T, Gutkind J S
Molecular Signalling Unit, National Institute of Dental Research, NIH, Bethesda, Maryland 20892.
Biochem Biophys Res Commun. 1994 Jun 15;201(2):603-9. doi: 10.1006/bbrc.1994.1744.
The finding of GTPase inhibiting mutations in genes for alpha subunits of Gs and Gi2 in certain endocrine tumors suggests that heterotrimeric G proteins might contribute to neoplasia. Expression of these activated forms of alpha s or alpha i2 in NIH 3T3 murine fibroblasts induces certain alterations in cell growth, but is weakly transforming. Mutationally activated forms of the alpha 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 alpha subunit of a novel G protein, G12, is itself transforming, and an activated mutant of alpha 12 behaves as one of the most potent oncogenes known. In this study, we have explored whether another member of the G alpha 12 family, G alpha 13, harbors transforming potential. Our data demonstrate that G alpha 13 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.
在某些内分泌肿瘤中，Gs和Gi2的α亚基基因存在GTP酶抑制突变，这一发现表明异源三聚体G蛋白可能与肿瘤形成有关。在NIH 3T3小鼠成纤维细胞中表达这些活化形式的αs或αi2会诱导细胞生长发生某些改变，但转化能力较弱。另一个G蛋白家族Gq的α亚基经突变激活后，在NIH 3T3细胞中具有完全致癌性，尽管效力很低。相比之下，我们最近发现，一种新型G蛋白G12的α亚基过表达本身就具有转化能力，α12的活化突变体表现为已知的最有效的致癌基因之一。在本研究中，我们探讨了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可以作为一种有效的显性作用致癌基因。这些发现强烈表明，G蛋白的G12家族代表了一类新型致癌基因。
