Signal transduction by interleukin 2 receptor beta chain: importance of the structural integrity as revealed by site-directed mutagenesis and generation of chimeric receptors.

The functional interleukin 2 receptor (IL-2R) consists of at least two IL-2 binding cell surface molecules, IL-2R alpha and IL-2R beta, the latter component being responsible for the intracellular growth signal transduction. In this study we attempted to identify the critical amino acid residues in the cytoplasmic domain of human IL-2R beta for such signal transduction by expressing mutated IL-2R beta cDNAs in a pro-B cell line, BAF-B03. We demonstrate that a single amino acid substitution within the 'serine-rich' cytoplasmic region of IL-2R beta (i.e. Leu299 changed to Pro) completely abrogates the receptor function in growth stimulation, but not in ligand binding. We also show that the murine erythropoietin receptor (EPO-R) is functional in BAF-B03, but that chimeric receptors, essentially possessing the IL-2R beta extracellular and a homologous region derived from EPO-R cytoplasmic domain, are not capable of transducing the IL-2-induced signal.