JAK3 MEDIATES C-MYC GENE-EXPRESSION INDUCED BY INTERLEUKIN-2

C-myc gene expression can be rapidly induced by IL-2 through intracell ular signal transduction which is triggered by the interaction between IL-2 and its receptor (IL-2R). JAK3 which associates to the intracell ular domain of IL-2R gamma may play a critical role in this process. T o reveal the action of JAK3 in c-myc induction, a chimeric receptor ge ne IL-2R alpha/gamma/Delta NJAK3 is constructed which consists of extr acellular domain derived from IL-2R alpha subunit (IL-2R alpha), the t ransmembrane sequence derived from IL-2R gamma and the cytoplasmic dom ain derived from the catalytic domain of JAK3 (Delta NJAK3), and then trhnsfccted this chimeric gene into mouse fibroblast cell line L929 be ta which had been transfected with IL-2R beta gene and stably expresse d IL-2R beta in high level. In the transfectants coexpressing IL-2R be ta and alpha/gamma/Delta NJAK3, the stimulation of IL-2 could intensiv ely induce c-myc gene expression. Because the whole cytoplasmic domain of IL-2R gamma which could recruit signaling molecules was replaced b y JAK3 and the c-myc could be still induced by IL-2 in this situation, the results here gave the direct evidence demonstrating that JAK3 pla ys an important role in c-myc gene expression induced by IL-2.