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

IL-2 R β是由IL-2诱导的细胞内信号转导所需的关键亚基，并且含有两个功能性胞质亚区（“富含丝氨酸”区和“酸性”区），分别富含丝氨酸残基和酸性氨基酸。IL-2 R β的“酸性”区域是与src家族蛋白酪氨酸激酶（PTK）p56 β结合所需的主要重要位点<lck>。我们最近的研究表明，IL-2 R β和p56 β之间的关联<lck>对于IL-2诱导的lck PTK活化是至关重要的。此外，还显示了另一个胞质区域，IL-2 R β的“富含丝氨酸”区域，也是激活lck PTK所需的。我们还表明，另一种SRC家族PTK，fyn PTK可以与IL-2 R β结合，并在IL-2刺激BAF-BO 3细胞后被激活，其中lck PTK的表达不可检测。此外，我们最近与Satoh博士等人（DNAX研究所，美国）的合作研究表明，IL-2刺激诱导ras蛋白的活化，推测是由src家族PTK介导的。有趣的是，IL-2诱导的src家族PTK的激活（以及IL-2诱导的ras蛋白的激活）导致c-fos和c-jun基因的诱导。另一方面，已经表明，由IL-2 R β的“富含丝氨酸”区域介导的一种迄今未知的信号导致c-myc基因诱导。因此，很明显，IL-2 R β与至少两种不同的细胞内信号传导途径相关，导致两组不同的核原癌基因（c-fos/c-jun和c-myc基因）的诱导。

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).