Activation of wild-type Ras (arrows) increases Myc (red) but not PI3K (green) signaling.


Acancerous form of Ras is dangerous because it intrudes on pathways where it is normally unwelcome, according to results from David Prober and Bruce Edgar (Fred Hutchinson Cancer Research Center, Seattle, WA).

The small GTPase Ras is stimulated by epidermal growth factor receptors in flies and vertebrates. Activated Ras initiates multiple cellular responses, including cell growth and differentiation. The importance of downstream effectors such as PI3K and Myc for each response has not been firmly determined, in part because their involvement varies depending on the cell culture system used.Prober and Edgar put some of this controversy to rest by examining how Ras can control cell growth in vivo. In the developing fly wing, both Myc and PI3K were up-regulated in clones of cells expressing an activated form of Ras, which increases cell size and growth rates. Although this form of Ras increased both Myc and PI3K, these pathways were activated independently of each other.

The activated Ras is one commonly found in mammalian tumors. But in normal cells, although wild-type Ras was required for Myc signaling, it had no effect on PI3K activity. Thus, says Edgar, “oncogenic Ras seems to short circuit endogenous signals,” by impinging on the PI3K pathway. The combined effects of Myc (which turns on transcription of translational machinery) and PI3K (which may increase nutrient import into cells) make oncogenic Ras a superpotent variant for increasing growth. ▪


Prober, D.A., and B.A. Edgar.
Genes Dev.