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NOVEL T CELL ACTIVATION GENE IN DEVELOPING NEURONS

发育中神经元中的新型 T 细胞激活基因

基本信息

批准号：
2890573
负责人：
MICHAEL B PRYSTOWSKY
金额：
$ 32.48万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-07-01 至 2000-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2890573
关键词：
DNA binding protein T lymphocyte behavioral /social science research tag gene expression gene mutation genetic regulatory element genetically modified animals interleukin 2 laboratory mouse laboratory rabbit leukocyte activation /transformation neurogenesis phosphorylation potassium channel psychoneuroimmunology tissue /cell culture

项目摘要

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.

DESCRIPTION (Adapted from applicant's abstract): Mental effects on physical 健康是由神经系统和免疫系统之间的相互作用介导的。这些系统通过共同的分子进行协调调节。给定细胞表面受体和可溶性介质的共同表达在这两个系统中，人们可能期望找到以下细胞内蛋白质：两个系统共有的并且可能涉及信号传输。调查人员从IL2刺激制备的cDNA文库中分离出cDNA序列，最近被鉴定为 KvBeta2 的克隆 T 淋巴细胞电压门控 K 通道亚基。钾通道维持膜电位并决定细胞的兴奋性。 β亚基似乎调节 K 通道的电导特性。 KvBeta2 的表达式为增殖淋巴细胞和出生后神经元。提出的假设是 Beta亚基表达影响淋巴细胞和神经元功能通过调节 K 通道电导。第一个目标将测试假设 IL2 驱动的 T 细胞需要 Beta 亚基表达增殖。研究人员表示，根据他们对 IL-2 的了解诱导基因表达，细胞周期进展的精确点是否被抑制将被确定。第二个目标是启动研究定义 Beta 亚基启动子和相应 DNA 中的顺式元件负责 IL2 诱导的 Beta 亚基的结合蛋白淋巴细胞中表达。第三个目标是依赖于激活 Beta 亚基上的磷酸化位点将在体外和体内测定体内。一旦发现特定的磷酸氨基酸，突变蛋白排除特异性磷酸化将准备好确定 IL2 驱动过程中 Beta 亚基功能磷酸化的要求增殖。确定淋巴细胞和淋巴细胞是否需要 Beta 亚基神经元发育和功能，Beta 亚基缺失纯合小鼠等位基因将被准备好。虽然这些动物可能存在免疫缺陷出生时，β亚基缺失对神经元发育的影响应该直到出生后神经元成熟才出现。这些研究将定义 KvBeta 亚基在神经和神经系统中的功能意义和免疫系统，并开始解决调节的分子机制组织特异性表达。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Lymphocyte-specific inducible expression of potassium channel beta subunits.

钾通道β亚基的淋巴细胞特异性诱导表达。

DOI：
10.1016/s0165-5728(97)00050-7
发表时间：
1997
期刊：
Journal of neuroimmunology
影响因子：
3.3
作者：
Autieri,MV;Belkowski,SM;Constantinescu,CS;Cohen,JA;Prystowsky,MB
通讯作者：
Prystowsky,MB

Protein kinase C-mediated phosphorylation of Kv beta 2 in adult rat brain.

成年大鼠脑中蛋白激酶 C 介导的 Kv beta 2 磷酸化。

DOI：
10.1023/b:nere.0000042215.92952.3d
发表时间：
2004
期刊：
Neurochemical research
影响因子：
4.4
作者：
Wang,Xintao;Zhang,Jie;Berkowski,StanM;Knowleg,Heather;Chandramouly,AB;Downens,Martha;Prystowsky,MichaelB
通讯作者：
Prystowsky,MichaelB

Developmental expression of voltage-gated potassium channel beta subunits.

电压门控钾通道β亚基的发育表达。