SIGNAL TRANSDUCTION BY INTERLEUKIN-2 RECEPTOR-BETA CHAIN - IMPORTANCE OF THE STRUCTURAL INTEGRITY AS REVEALED BY SITE-DIRECTED MUTAGENESIS AND GENERATION OF CHIMERIC RECEPTORS

被引:38
作者
MORI, H [1 ]
BARSOUMIAN, EL [1 ]
HATAKEYAMA, M [1 ]
TANIGUCHI, T [1 ]
机构
[1] OSAKA UNIV,INST MOLEC & CELLULAR BIOL,1-3 YAMADAOKA,SUITA,OSAKA 565,JAPAN
关键词
INTERLEUKINS; HIGH-AFFINITY RECEPTOR; INTERNALIZATION;
D O I
10.1093/intimm/3.2.149
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:149 / 156
页数:8
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