RAS ACTIVATION LEADS TO CELL-PROLIFERATION OR APOPTOTIC CELL-DEATH UPON INTERLEUKIN-2 STIMULATION OR LYMPHOKINE DEPRIVATION, RESPECTIVELY

Lymphokine-dependent cells undergo apoptosis upon lymphokine withdrawa l. We describe that lymphokine deprivation of the interleukin (IL)-2- or IL-4-dependent mouse T cell line TS1 alpha beta induces Ras activat ion which plays a role in programed cell death, since blocking Ras act ivity reduces the induction of apoptosis. Induction of apoptosis by ly mphokine deprivation can be prevented by expression of the Bcl-2 prote in. Rescue from cell death by IL-2 also promotes Ras activation, but, in contrast to lymphokine withdrawal, stimulates Bcl-2 expression. IL- 4-induced cell survival is Ras- and Bcl-2 independent. These results a re compatible with a model in which cell proliferation requires the si multaneous induction of at least two pathways which act in combination to prevent cell death.