SIGNAL TRANSDUCTION MECHANISMS MEDIATED BY INTERLEUKIN-9

描述：本提案的主要重点是了解 控制白细胞介素-9生物特异性的机制。 的 第一个具体目标将是描述上游和下游 由白细胞介素-9介导的信号传导事件。 IRS的作用 将测定IL-9信号传导中的胰岛素受体底物蛋白。 这将通过产生用于过表达的表达质粒来完成， IRS蛋白的cDNA反义表达，产生显性阴性 IRS蛋白的突变体，并比较信号事件和生物学特性。 亲本和转染细胞系的影响。 IRS相关分子 也将进行分析。 IL-9受体配体结合的相互作用 亚基，IRS蛋白和JAK 1将通过产生突变体进行研究。 这些蛋白质和研究这些分子的相互作用。 主 将通过以下方法鉴定和检查由IL-9激活的应答基因： 差异显示 特异性目标2将决定IL-9的结构域， 受体，连接上游和下游信号和生物 应答 这将在很大程度上是通过诱变研究完成的。 IL-9受体及其对配体结合、信号传导和 细胞反应。

DESCRIPTION: The major focus of this proposal is to understand the mechanisms controlling the biological specificity of interleukin-9. The first specific aim will be to characterize the upstream and downstream signaling events mediated by interleukin-9. The role of IRS (insulin-receptor substrate) proteins in IL-9 signalling will be determined. This will be done by generating expression plasmids for overexpression and antisense expression of cDNAs for IRS proteins, generating dominate negative mutants for IRS proteins, and comparing the signaling events and biological effects of parental and transfected cell lines. IRS associated molecules will also be analyzed. The interaction of IL-9 receptor ligand-binding subunit, IRS proteins, and JAK1 will be studied by generating mutants of these proteins and studying the interaction of these molecules. The primary response genes activated by IL-9 will be identified and examined through differential display. Specific Aim 2 will determine the domains of the IL-9 receptor that connect the upstream and downstream signals and biological responses. This will largely be accomplished by mutagenesis studies of the IL-9 receptor and subsequent effects on ligand binding, signalling, and cellular responses.