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 IL-2 regulates cell growth, few studies have dissected the pathways involved in promoting cell survival or the coupling of these pathways to the receptor. In the present study, using the pre-B cell line Baf-B03 transfected with a truncated form of the IL-2 receptor (IL-2R) beta chain, we demonstrate that IL-2-dependent cell survival requires only the N-terminal 350 amino acids of the IL-2Rbeta chain. IL-2-dependent survival of cells expressing the truncated receptor correlates with increases in receptor-associated phosphatidylinositol 3-kinase (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) response. The requirement for IL-2-induced PI3K activity in suppressing the onset of apoptotic cell death is discussed.
Ciprés
A
A
Department of Immunology and Oncology, Centro Nacional de Biotecnologia, Madrid, Spain.
Gala
S
S
Martinez-A
C
C
Mérida
I
I
Williamson
P
P
D017209:Apoptosis; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D008894:Milk Proteins; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D015375:Receptors, Interleukin-2 / Q000502:physiology*; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000502:physiology; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D004268:DNA-Binding Proteins; D007376:Interleukin-2; D007377:Interleukin-3; D008894:Milk Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D015375:Receptors, Interleukin-2; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D051020:bcl-X Protein; D019869:Phosphatidylinositol 3-Kinases