The viability of vertebrate cells depends on survival factors which ac
tivate signal transduction pathways that suppress apoptosis. Defects i
n anti-apoptotic signalling pathways are implicated in many pathologie
s including cancer, in which apoptosis induced by deregulated oncogene
s must be forestalled for a tumour to become established. Phosphatidyl
inositol-3-kinase (PI(3)K) is involved in the intracellular signal tra
nsduction of many receptors and has been implicated in the transductio
n of survival signals in neuronal cells(1). We therefore examined the
role of PI(3)K, its upstream effector Ras(2), and its putative downstr
eam protein kinase effecters PKB/Akt(3,4) and p70(S6K) (ref. 5) in the
modulation of apoptosis induced in fibroblasts by the oncoprotein c-M
yc. Here we show that Ras activation of PI(3)K suppresses c-Myc-induce
d apoptosis through the activation of PKB/Akt but not p70(S6K). Howeve
r, we also found that Ras is an effective promoter of apoptosis, throu
gh the Raf pathway. Thus Ras activates contradictory intracellular pat
hways that modulate cell viability. Induction of apoptosis by Ras may
be an important factor in limiting the expansion of somatic cells that
sustain oncogenic ras mutations.