POTENT TRANSFORMING ACTIVITY OF THE G(13) ALPHA-SUBUNIT DEFINES A NOVEL FAMILY OF ONCOGENES

The finding of GTPase inhibiting mutations in genes for a subunits of G(s) and G(i2) 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, G(q) 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, G(12), 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 G(12) family of G proteins represents a novel class of oncogenes. (C) 1994 Academic Press, Inc.