KINASE ENCODING PROTO-ONCOGENES IN IL-2 SIGNAL TRANSDUCT

淋巴因子白介素2(IL2)是一种重要的调节因子。 淋巴细胞的生长和免疫反应，并开始发现临床 用于治疗癌症和免疫紊乱。更多的知识 因此，IL2信号转导的分子机制可能 最终有助于改进体内的药理操作 免疫反应或调节淋巴瘤和白血病细胞的生长。 尽管IL-2及其受体基因的克隆和广泛的 在使用各种方法进行调查时，人们对 IL-2的信号转导机制。与许多其他增长因素不同 受体，淋巴细胞上的IL2结合分子缺乏酪氨酸激酶 活性，但酪氨酸和丝氨酸/苏氨酸磷酸化 细胞内蛋白是IL-2刺激的T细胞的快速反应。 因此，很明显，IL2及其受体必须调节 淋巴细胞中的激活酶。 最近，我们发现IL2诱导酪氨酸磷酸化。 丝氨酸-苏氨酸专一性的RAF-1激酶活性升高 该蛋白与MSV-3611逆转录病毒的转化基因具有同源性。 此前已有研究表明，该激酶参与了 几种类型细胞的有丝分裂和恶变， 包括淋巴细胞。我们将探索负责的机制 白介素2刺激下RAF-1蛋白的磷酸化和活化 T细胞。此外，我们还将研究该激酶对血管内皮细胞 调节T细胞的生长。这些研究将有助于 提高了对IL2作用的细胞内机制的理解，以及 可能提供对参与的生长因子/癌基因网络的洞察 白血病和淋巴瘤的发展和进展。

The lymphokine interleukin-2 (IL2) is a critical regulator of lymphocyte growth and immune responses, and is beginning to find clinical uses for the treatment of cancer and immune disorders. Greater knowledge of the molecular mechanisms of IL2signal transduction, therefore, could ultimately contribute to improved pharmacological manipulation of in vivo immune responses or modulation of lymphoma and leukemic cell growth. Despite cloning of IL2 and its receptor genes and extensive investigations using a variety of approaches, little is known about the mechanisms of IL2-signal transduction. Unlike many other growth factor receptors, the IL2-binding molecules on lymphocytes lack tyrosine-kinase activity, and yet both tyrosine and serine/ threonine phosphorylation of intracellular proteins are rapid events in IL2-stimulated T-cells. Clearly, therefore, IL2 and its receptor must regulate the activity of kinases in lymphocytes. Recently, we have found that IL2 induces tyrosine phosphorylation and elevated activity of the RAF-1 kinase, a serine-threonine-specific kinase with homology to the transforming gene of MSV-3611 retrovirus. This kinase has been implicated previously in the regulation of mitogenesis and malignant transformation in several types of cells, including lymphocytes. We will explore the mechanisms responsible for phosphorylation and activation of the RAF-1 kinase in IL2-stimulated T-cells. Further we will investigate the effects of this kinase on the regulation of T-cell growth. These studies will contribute to an improved understanding of the intracellular mechanisms of IL2 action, and may provide insights into the growth factor/oncogene networks involved in the development and progression of leukemias and lymphomas.