Critical role of the interleukin 2 (IL-2) receptor gamma-chain-associated Jak3 in the IL-2-induced c-fos and c-myc, but not bcl-2, gene induction.
Critical role of the interleukin 2 (IL-2) receptor gamma-chain-associated Jak3 in the IL-2-induced c-fos and c-myc, but not bcl-2, gene induction.
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白细胞介素 2 (IL-2) 受体 γ 链相关 Jak3 在 IL-2 诱导的 c-fos 和 c-myc（而非 bcl-2）基因诱导中发挥关键作用。
DOI：
10.1073/pnas.92.19.8724
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发表时间：
1995
影响因子：
11.1
通讯作者：
Taniguchi,T
中科院分区：
文献类型：
--
作者：
Kawahara,A;Minami,Y;Miyazaki,T;Ihle,JN;Taniguchi,T
白细胞介素2受体（IL-2 R）由三个亚基组成，即IL-2 R α、IL-2 R β c和IL-2 R γ c链。研究表明，两种Janus家族蛋白酪氨酸激酶（PTK）Jak 1和Jak 3分别与IL-2 R β c和IL-2 R γ c相关，并且它们的PTK活性在IL-2刺激后增加。具有C-末端PTK结构域截短的Jak 3突变体缺乏其固有激酶活性，但仍能与IL-2 R γ c结合。在对IL-2或IL-3应答的造血细胞系F7中，该Jak 3突变体的过表达导致IL-2诱导的Jak 1/Jak 3 PTKs活化和细胞增殖的选择性抑制。在IL-2信号转导的三个靶核原癌基因中，发现c-fos和c-myc基因受损，而bcl-2基因未受损。另一方面，在F7细胞中，IL-2 R γ c链的显性负性形式的过表达（其缺乏其大部分胞质结构域）导致所有三种原癌基因的抑制。这些结果为Jak 3在IL-2信号传导中的关键作用提供了进一步的分子基础，并且还表明IL-2 R诱导bcl-2基因的Jak PTK非依赖性信号传导途径。
The interleukin 2 receptor (IL-2R) consists of three subunits, the IL-2R alpha, IL-2R beta c, and IL-2R gamma c chains. Two Janus family protein tyrosine kinases (PTKs), Jak1 and Jak3, were shown to associate with IL-2R beta c and IL-2R gamma c, respectively, and their PTK activities are increased after IL-2 stimulation. A Jak3 mutant with truncation of the C-terminal PTK domain lacks its intrinsic kinase activity but can still associate with IL-2R gamma c. In a hematopoietic cell line, F7, that responds to either IL-2 or IL-3, overexpression of this Jak3 mutant results in selective inhibition of the IL-2-induced activation of Jak1/Jak3 PTKs and of cell proliferation. Of the three target nuclear protooncogenes of the IL-2 signaling, c-fos and c-myc genes, but not the bcl-2 gene, were found to be impaired. On the other hand, overexpression of the dominant negative form of the IL-2R gamma c chain, which lacks most of its cytoplasmic domain, in F7 cells resulted in the inhibition of all three protooncogenes. These results provide a further molecular basis for the critical role of Jak3 in IL-2 signaling and also suggest a Jak PTK-independent signaling pathway(s) for the bcl-2 gene induction by IL-2R.