An IL-2 receptor beta subdomain that controls Bcl-X-L expression and cell survival

IL-2 binding to its high-affinity receptor regulates signaling events that control both lymphocyte cell survival and cell cycle progression. Although many studies have examined the mechanisms by which lL-2 regulates cell grow th, few studies have dissected the pathways involved in promoting cell surv ival or the coupling of these pathways to the receptor. In the present stud y, using the pre-B cell line Baf-B03 transfected with a truncated form of t he IL-2 receptor (IL-2R) beta chain, we demonstrate that IL-2-dependent cel l survival requires only the N-terminal 350 amino acids of the IL-2R beta c hain. IL-2-dependent survival of cells expressing the truncated receptor co rrelates with increases in receptor-associated phosphatidylinositol 3-kinas e (PI3K) activity and expression of Bcl-X-L, but not with changes in c-Myc expression or proliferation. Inhibition of the PI3K pathway in these cells, but not in cells expressing the wild-type receptor, has a marked effect on the capacity of IL-2 to prevent cell death and diminishes the Bcl-X-L resp onse. The requirement for IL-2-induced PI3K activity in suppressing the ons et of apoptotic cell death is discussed.