Interleukin 2 induces tyrosine phosphorylation and activation of p72-74 Raf-1 kinase in a T-cell line.
Interleukin 2 induces tyrosine phosphorylation and activation of p72-74 Raf-1 kinase in a T-cell line.
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Interleukin 2 可诱导 T 细胞系中的酪氨酸磷酸化和 p72-74 Raf-1 激酶的激活。
DOI：
10.1073/pnas.88.4.1227
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发表时间：
1991
影响因子：
11.1
通讯作者：
Reed,J
中科院分区：
文献类型：
--
作者：
Turner,B;Rapp,U;App,H;Greene,M;Dobashi,K;Reed,J
白介素2(IL-2)是T细胞在抗原或有丝分裂刺激下产生的一种淋巴因子，是T细胞增殖的重要调节因子。尽管IL-2与其受体的结合已经被很好地描述，但IL-2将其信号从细胞膜传递到细胞内部的分子机制却知之甚少。像大多数其他生长因子一样，IL-2导致其靶细胞内蛋白质的快速磷酸化。然而，与许多其他生长因子不同的是，已知的IL-2受体亚单位缺乏酪氨酸特异的激酶活性，并且对其活性受IL-2调节的激酶知之甚少。在这里，我们证明了IL-2(而不是IL-4)诱导依赖于IL-2的小鼠T细胞系CTLL-2中由c-Raf-1原癌基因编码的P72-74丝氨酸/苏氨酸特异性激酶的快速磷酸化，并且这种磷酸化与含有P72-74 Raf-1的免疫复合体中的激酶活性增加有关。IL-2诱导的Raf-1激酶活性升高的浓度依赖关系与IL-2刺激的CTLL-2细胞增殖密切相关。此外，IL-2刺激的P72-74Raf-1的大部分磷酸化发生在酪氨酸上。据我们所知，Raf-1是第一个被鉴定的由IL-2调节的酪氨酸激酶的内源性底物。
Interleukin 2 (IL-2) is a lymphokine, produced by T cells upon antigenic or mitogenic stimulation, that is a critical regulator of T-cell proliferation. Although the binding of IL-2 to its receptor has been well characterized, the molecular mechanisms by which IL-2 transmits its signal from the membrane to the interior of the cell are poorly understood. Like most other growth factors, IL-2 causes rapid phosphorylation of proteins within its target cells. Unlike many other growth factors, however, the known subunits of the IL-2 receptor lack tyrosine-specific kinase activity, and little is known about the kinases whose activities are regulated by IL-2. Here we show that IL-2 (but not IL-4) induces rapid phosphorylation of the p72-74 serine/threonine-specific kinase encoded by the c-Raf-1 protooncogene in an IL-2-dependent murine T-cell line, CTLL-2, and that this phosphorylation is associated with increased kinase activity in p72-74 Raf-1-containing immune complexes. The concentration dependence of IL-2-mediated elevations in Raf-1 kinase activity correlated well with IL-2-stimulated proliferation of CTLL-2 cells. Furthermore, much of the IL-2-stimulated phosphorylation of p72-74 Raf-1 occurred on tyrosines. To our knowledge, the Raf-1 kinase represents the first endogenous substrate of an IL-2-regulated tyrosine kinase to be identified.