Potent transforming activity of the G13 alpha subunit defines a novel family of oncogenes.
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.
Xu
N
N
Molecular Signalling Unit, National Institute of Dental Research, NIH, Bethesda, Maryland 20892.
Voyno-Yasenetskaya
T
T
Gutkind
J S
JS
D016475:3T3 Cells; D000818:Animals; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D019204:GTP-Binding Proteins / Q000096:biosynthesis*; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D005810:Multigene Family; D016296:Mutagenesis; D009857:Oncogenes; D016366:Open Reading Frames; D014162:Transfection
D046911:Macromolecular Substances; D019204:GTP-Binding Proteins