Analysis of signal transduction mediated by the cytokine receptor(s)

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IL-2Rbeta is a critical subunit required for the intracellular signal transduction induced by IL-2 and contains the two functional cytoplasmic subregions( the "serine-rich" and the "acidic" regions), rich in serine residues and in acidic amino acids, respectively. The "acidic" region of IL-2Rbeta is a primarily important site required for associating with a src-family protein tyrosine kinase(PTK), p56^<lck>. Our recent study shows that the association between IL-2Rbeta and p56^<lck> is critical for the IL-2-induced activation of lck PTK. In addition, it was shown that another cytoplasmic region, the "serine-rich" region of IL-2Rbeta, is also required for activating lck PTK. We have also shown that another src-family PTK,fyn PTK can associate with IL-2Rbeta and is activated following IL-2 stimulation of BAF-BO3 cells where expression of lck PTK is not detectable. Futhermore, our recent collaborative study with Dr. Satoh et al. (DNAX Research Institute, USA) has in dicated that IL-2 stimulation induces the activation of the ras protein, presumably mediated by a src-family PTK(s). Interestingly, the IL-2-induced activation of a src-family PTK(s)(as well as the IL-2-induced activation of the ras protein) leads to the induction of the c-fos and c-jun genes. On the other hand, it was shown that an as yet unknown signal(s), mediated by the "serine-rich" region of IL-2Rbeta, leads to the c-myc gene induction. Thus, it became evident that IL-2Rbeta is linked to at least two distinct intracellular signaling path ways, leading to the induction of the two different sets of nuclear proto-oncogenes(c-fos/c-jun and c-myc genes).