title: Signal transduction by interleukin 2 receptor beta chain: importance of the structural integrity as revealed by site-directed mutagenesis and generation of chimeric receptors.
abstract: 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.
authors.affiliation: Institute for Molecular and Cellular Biology, Osaka University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Mori
authors.forename: E L
authors.initials: EL
authors.lastname: Barsoumian
authors.forename: M
authors.initials: M
authors.lastname: Hatakeyama
authors.forename: T
authors.initials: T
authors.lastname: Taniguchi
mesh_terms: D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D002678:Chimera / Q000235:genetics*; D004921:Erythropoietin / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed / Q000235:genetics*; D010957:Plasmids; D015375:Receptors, Interleukin-2 / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D004921:Erythropoietin