3 DISTINCT IL-2 SIGNALING PATHWAYS MEDIATED BY BCL-2, C-MYC, AND LCK COOPERATE IN HEMATOPOIETIC-CELL PROLIFERATION

Two interleukin-2 receptor-dependent signaling pathways have thus far been identified: the c-fos/c-jun induction pathway mediated by src fam ily protein-tyrosine kinases and the c-myo induction pathway. Here, we provide evidence for the existence of a third, rapamycin-sensitive pa thway, which results in the induction of another proto-oncogene, bcl-2 . In the hematopoietic cell line BAF-B03, the expression of any two of lckF505 (an active form of p56(lck)), Bcl-2, or c-Myc is sufficient t o promote transit of the cell cycle, regardless of the activation stat e of the third pathway. We also provide evidence that epidermal growth factor receptor signaling may act through the same pathway that invol ves p56(lck). These studies demonstrate a novel approach to dissecting signaling pathways regulating cellular proliferation.