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

细胞因子受体介导的信号转导分析

基本信息

批准号：
03670251
负责人：
MINAMI Yasuhiro
金额：
$ 1.15万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

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).

IL-2RBETA是由IL-2诱导的细胞内信号转导所需的关键亚基，并包含两个功能性细胞质亚区域（“丝氨酸富含”和“酸性”区域），分别富含丝氨酸残基和酸性氨基酸。 IL-2RBETA的“酸性”区域是与SRC家族蛋白酪氨酸激酶（PTK），p56^<lck>关联所需的主要重要部位。我们最近的研究表明，IL-2rbeta和p56^<lck>之间的关联对于IL-2诱导的LCK PTK激活至关重要。此外，还表明另一个细胞质区域是IL-2rbeta的“丝氨酸富”区域，也需要激活LCK PTK。我们还表明，另一个SRC家庭PTK FYN PTK可以与IL-2RBETA相关，并在无法检测到LCK PTK表达的BAF-BO3细胞后激活。 Futhermore，这是我们最近与Satoh等人的合作研究。（美国DNAX研究所）在介绍的IL-2刺激中诱导了RAS蛋白的激活，这可能是由SRC家庭PTK（S）介导的。有趣的是，IL-2诱导的SRC家庭PTK（S）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，结果表明，由IL-2RBETA的“丝氨酸富”区域介导的尚未知道的信号导致C-MYC基因诱导。因此，很明显，IL-2RBETA与至少两种不同的细胞内信号通路方式相关联，导致诱导了两种不同的核原始核基因（C-FOS/C-J-JUN和C-MYC基因）。