GENE-TRANSFER OF THE INTERLEUKIN (IL)-2 RECEPTOR-BETA CHAIN INTO AN IL-7-DEPENDENT PRE-B-CELL LINE PERMITS IL-2-DRIVEN PROLIFERATION - TYROSINE PHOSPHORYLATION OF SHC IS INDUCED BY IL-2 BUT NOT IL-7

Expression of the interleukin (IL)-2 receptor beta chain in the IL-7 dependent pre-B cell line IxN/2B permitted growth in presence of either IL-2 or IL-7, allowing for a direct comparison of intracellular signaling events. Protein tyrosine phosphorylation was essential for IL-2- and IL-7-induced signal transduction since the tyrosine kinase inhibitor herbimycin A blocked proliferation in response to both factors. Western blot analysis of tyrosine-phosphorylated proteins revealed that both IL-2 and IL-7 stimulation led to enhanced phosphorylation of proteins of 170-, 145-, 115- and 99-kDa, as well as induction of phosphorylation of a 96-kDa protein. However, a 55- and a 155-kDa protein were only phosphorylated after IL-2 stimulation. The 55-kDa protein specifically phosphorylated by IL-2 could be identified as p52(shc) which has recently been shown to be critically involved in Ras activation. Shc tyrosine phosphorylation as a result of IL-2 stimulation was consistently found in CTLL-2 cells and human T lymphoblasts. Taken together our results indicate that the IL-2- and IL-7-stimulated intracellular pathways are partially different and that Shc is a target of IL-2-, but not IL-7-, stimulated tyrosine phosphorylation.