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Phosphatase Regulation of IL 4 Receptor Expression

IL 4 受体表达的磷酸酶调节

基本信息

批准号：
6362250
负责人：
HUA HUANG
金额：
$ 10.8万
依托单位：
LOYOLA UNIVERSITY CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-03-01 至 2003-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6362250
关键词：
cytokine receptors enzyme activity helper T lymphocyte interleukin 4 laboratory mouse phosphorylation protein tyrosine phosphatase receptor expression tissue /cell culture

项目摘要

Studies are proposed to analyze the mechanisms through which IL- 4Ralpha chain expression in regulated, both at the basal levels and in its induction during immune responses. In particular, to examine the role of protein tyrosine phosphatases (PTPases) in determining the level of IL-4Ralpha chain expression in basal and in the IL-4-induction state. To study the role PTPases in regulating IL-4Ralpha chain expression, experiements are proposed to: 1. Study the role of SHP-1 in regulating expression of IL-4Ralpha chain. a. Examine the expression of IL-4Ralpha chain and other type I cytokine receptors ofmotheaten mice. b. Examine whether SHP-1 directly regulates IL-4Ralpha chain expression. 2. Study the role of PTPases in regulating induced expression of IL-4Ralpha chain. a. Establish whether, in the absence of PTPase activity, induced IL- 4Ralpha chains become degraded. b. To determine whether hyperphosphorylation of the IL-4Ralpha chain is a prerequisite for IL-4Ralpha chain degradation; if it is, to determine what sites on the receptor are critically important. c. Determine what segments of IL-4Ralpha chain is/are required for the interaction with SHP-1 and other PTPases and effect of these interaction on IL-4Ralpha chain expression. 3. To study the cellular sites and mechanisms of IL-4Ralpha chain degradation. IL-4 play the key role in mediating any biological functions, including affecting the outcomes of many infectious and autoimmune diseases. The proposed study will provide an insight into a novel mechanism regulating IL-4 receptor signaling.

有人建议研究分析IL-4R链在免疫反应的基础水平和诱导过程中表达调节的机制。特别是，检测蛋白酪氨酸磷酸酶(PTPase)在决定IL-4R在基础状态和IL-4诱导状态下的链表达水平中的作用。为了研究PTPase在调节IL-4Rα链表达中的作用，提出了以下实验：1.研究SHP-1在调节IL-4Rα链表达中的作用。A.检测母鼠IL-4Ra链等I型细胞因子受体的表达。B.检测SHP-1是否直接调节IL-4Ra链的表达。2.研究PTPase在调节IL-4Rα链诱导表达中的作用。A.确定在没有PTPase活性的情况下，诱导的IL-4Rα链是否被降解。B.确定IL-4R链过度磷酸化是否是IL-4R链降解的先决条件；如果是，确定受体上的哪些部位是至关重要的。C.确定与SHP-1和其他PTPase相互作用所需的IL-4Rα链的哪些片段，以及这些相互作用对IL-4Rα链表达的影响。3.研究IL-4Rα链降解的细胞部位和机制。IL-4在任何生物学功能中起着关键作用，包括影响许多感染性和自身免疫性疾病的转归。这项拟议的研究将为调节IL-4受体信号的新机制提供一个新的见解。