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 withdrawal. We describe that lymphokine deprivation of the interleukin (IL)-2- or IL-4-dependent mouse T cell line TS1 alpha beta induces Ras activation which plays a role in programmed cell death, since blocking Ras activity reduces the induction of apoptosis. Induction of apoptosis by lymphokine deprivation can be prevented by expression of the Bcl-2 protein. 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 are compatible with a model in which cell proliferation requires the simultaneous induction of at least two pathways which act in combination to prevent cell death.
Gómez
J
J
Department of Immunology and Oncology, Centro Nacional de Biotecnología-CSIC, Universidad Autónoma, Madrid, Spain. jgomez@cnb.uam.es
Martínez
C
C
Fernández
B
B
García
A
A
Rebollo
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D008222:Lymphokines / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D014162:Transfection / Q000276:immunology; D019014:fas Receptor / Q000502:physiology; D018631:ras Proteins / Q000378:metabolism* / Q000502:physiology
D007376:Interleukin-2; D008222:Lymphokines; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D018631:ras Proteins