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Miyazaki, T, Liu, ZJ, Kawahara, A, Minami, Y, Yamada, K, Tsujimoto, Y, Barsoumian, EL, Permutter, RM and Taniguchi, T (1995) Three distinct IL-2 signaling pathways mediated by bcl-2, c-myc, and lck cooperate in hematopoietic cell proliferation. Cell 81:223-31
Two interleukin-2 receptor-dependent signaling pathways have thus far been identified: the c-fos/c-jun induction pathway mediated by src family protein-tyrosine kinases and the c-myc induction pathway. Here, we provide evidence for the existence of a third, rapamycin-sensitive pathway, 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 p56lck), Bcl-2, or c-Myc is sufficient to promote transit of the cell cycle, regardless of the activation state of the third pathway. We also provide evidence that epidermal growth factor receptor signaling may act through the same pathway that involves p56lck. These studies demonstrate a novel approach to dissecting signaling pathways regulating cellular proliferation.
Animals; Apoptosis/physiology; B-Lymphocytes/drug effects; B-Lymphocytes/physiology; Cell Division/drug effects; Epidermal Growth Factor/pharmacology; Gene Expression Regulation/drug effects; Hematopoietic Stem Cells/drug effects; Hematopoietic Stem Cells/physiology; Interleukin-2/pharmacology; Lymphocyte Specific Protein Tyrosine Kinase p56(lck); Mice; Models, Biological; Oncogene Proteins/genetics; Oncogene Proteins/metabolism; Polyenes/pharmacology; Protein-Tyrosine Kinases/genetics; Protein-Tyrosine Kinases/metabolism; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins c-myc/genetics; Proto-Oncogene Proteins c-myc/metabolism; Receptor, Epidermal Growth Factor/metabolism; Signal Transduction/physiology; Sirolimus
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