NOVEL T CELL ACTIVATION GENE IN DEVELOPING NEURONS

描述(摘自申请者的摘要)：心理对身体的影响 健康是通过神经系统和免疫系统之间的相互作用来调节的。 这些系统通过共同的分子进行协调调节。vt.给出 细胞表面受体和可溶性介质的共同表达 这两个系统，人们可能会发现细胞内的蛋白质是 为两个系统所共有，并可能参与信令。调查人员 从IL-2刺激的cDNA文库中分离出一条cDNAs序列， 新近被鉴定为KvBeta2的克隆T淋巴细胞 电压门控K通道子单元。钾通道维持膜 并确定细胞的兴奋性。β亚基似乎 调节K通道的电导特性。KvBeta2表示为 增殖的淋巴细胞和出生后的神经元。提出的假设是 β亚基的表达影响淋巴细胞和神经元的功能 通过对K通道电导的调制。第一个目标将测试 假设IL-2驱动的T细胞需要β亚基表达 扩散。研究人员表示，凭借他们对IL-2的了解 诱导基因表达，细胞周期进程的确切时间点 是被禁止的将被确定。在第二个目标中，将启动研究 确定Beta亚单位启动子和相应DNA中的顺式元件 IL-2诱导的β亚基的结合蛋白 在淋巴细胞中的表达。第三个目标是依赖于激活 β亚基上的磷酸化位点将在体外和 活着。一旦发现特定的磷酸氨基酸，突变的蛋白质 排除特定的磷酸化将被准备来确定 白细胞介素2驱动过程中β亚基功能的磷酸化需求 扩散。确定淋巴细胞是否需要β亚基和 神经发育和功能，纯合子小鼠的Beta亚基缺失 将会准备好等位基因。虽然这些动物可能是免疫缺陷 出生，β亚基缺失对神经元发育的影响应该是 直到出生后神经元成熟时才出现。这些研究将 确定KvBeta亚基在两种神经细胞中的功能意义 和免疫系统，并开始解决分子机制调节 组织特异性表达。

DESCRIPTION (Adapted from applicant's abstract): Mental effects on physical health are mediated by interactions between the nervous and immune systems. These systems are coordinately regulated through common molecules. Given the common expression of cell surface receptors and soluble mediators in both systems, one might expect to find intracellular proteins that are common to both systems and may be involved in signaling. The investigators isolated a cDNA sequence from a cDNA library prepared from IL2-stimulated, cloned T lymphocytes which has recently been identified as the KvBeta2 subunit of voltage-gated K channels. Potassium channels maintain membrane potential and determine the excitability of cells. Beta subunits appear to regulate the conductance properties of K channels. KvBeta2 is expressed in proliferating lymphocytes and postnatal neurons. The hypothesis proposed is that Beta subunit expression affects lymphocyte and neuronal function through modulation of K channel conductance. The first aim will test the hypothesis that Beta subunit expression is required for IL2-driven T cell proliferation. The investigators indicate that with their knowledge of IL-2 induced gene expression, the precise point at which cell cycle progression is inhibited will be determined. In a second aim, studies will be initiated to define cis elements in a Beta subunit promoter and corresponding DNA binding proteins which are responsible for IL2-induced Beta subunit expression in lymphocytes. In a third aim, activation-dependent phosphorylation sites on Beta subunits will be determined in vitro and in vivo. Once specific phosphoamino acids are found, mutant proteins precluding specific phosphorylation will be prepared to determine the requirement of phosphorylation for Beta subunit function during IL2-driven proliferation. To determine if Beta subunit is required for lymphocytic and neuronal development and function, mice homozygous for a Beta subunit null allele will be prepared. While these animals may be immunodeficient at birth, the effect of Beta subunit deletion on neuronal development should not appear until postnatal neuronal maturation occurs. These studies will define the functional significance for KvBeta subunits in both the nervous and immune systems and begin to address molecular mechanisms regulating tissue specific expression.