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.