Phosphatase Regulation of IL 4 Receptor Expression

IL 4 受体表达的磷酸酶调节

• 批准号: 2883819
• 负责人: HUA HUANG
• 金额: $ 16.2万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至 2002-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2883819
• 关键词: cytokine receptors; enzyme activity; helper T lymphocyte; interleukin 4; laboratory mouse; phosphorylation; protein tyrosine phosphatase; receptor expression; tissue /cell culture

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.

本文拟对IL-4 R α链在基础水平和诱导免疫应答过程中的表达调控机制进行分析。 特别是，检查蛋白酪氨酸磷酸酶（PTPases）在确定基础和IL-4诱导状态下IL-4 R α链表达水平中的作用。为了研究PTPases在调节IL-4 R α链表达中的作用，本实验拟：1.研究SHP-1对IL-4 R α链表达的调控作用。 a.检测IL-4 R α链及其它I型细胞因子受体在小鼠烫伤后的表达。 B.检查SHP-1是否直接调节IL-4 R α链表达。 2.研究PTPases对IL-4 R α链诱导表达的调节作用。 a.确定在不存在PTK活性的情况下，诱导的IL-4 R α链是否降解。 B.确定IL-4 R α链的过度磷酸化是否是IL-4 R α链降解的先决条件;如果是，确定受体上哪些位点至关重要。 C.确定与SHP-1和其他PTPases相互作用所需的IL-4 R α链的哪些片段以及这些相互作用对IL-4 R α链表达的影响。 3.目的研究IL-4 R α链降解的细胞部位和机制。IL-4在介导任何生物学功能中起关键作用，包括影响许多感染性和自身免疫性疾病的结果。 这项研究将为IL-4受体信号转导的新机制提供一个新的视角。