CHARACTERIZATION OF THE HUMAN INTERLEUKIN-2 RECEPTOR GAMMA-CHAIN GENE

The interleukin-2 (IL-2) receptor gamma chain is an essential componen t of high and intermediate affinity IL-2 receptors (IL-2Rs), playing c ritical roles for ligand binding and internalization. We report here t he isolation and characterization of the genomic locus for human IL-2R gamma, which, like IL-2Rbeta, is a member of the cytokine receptor sup erfamily. The IL-2Rgamma gene is composed of eight exons and seven int rons and spans approximately 4.2 kilobases. Analogous to the IL-2Rbeta gene, the two pairs of conserved cysteines typical of cytokine recept or superfamily proteins are located in adjacent exons, and the conserv ed WSXWS motif is located in the exon preceding the one that encodes t he transmembrane domain and a Small part of the cytoplasmic domain. In each gene, the remainder of the cytoplasmic domain is encoded by the final two exons. Southern blot analysis suggests that IL-2Rgamma is en coded by a single copy gene. Cross-hybridizing sequences were detected in DNA derived from a number of other mammalian species but not from yeast. Primer extension analysis and ribonuclease protection assays re vealed that there are three principal transcription initiation sites l ocated 32-38 nucleotides 5' to the translation initiation AUG codon. T hese sites are upstream of the 5' end of the published IL-2Rgamma cDNA sequence. The region 5' to the transcription initiation sites exhibit ed promoter activity when cloned upstream of the luciferase reporter g ene. With this study, the organization of the genes encoding all three chains (alpha, beta, and gamma) of the IL-2 receptor has been determi ned and promoters for each identified.