The Cytoskeleton, Rafts and the Interleukin-2 Receptor

细胞骨架、筏和 IL-2 受体

• 批准号: 6799932
• 负责人: JENS GOEBEL
• 金额: $ 11.96万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6799932
• 关键词: T lymphocyte; biological signal transduction; cell biology; cell component structure /function; clinical research; confocal scanning microscopy; cytokine receptors; cytoskeletal proteins; genetically modified animals; immunoprecipitation; interleukin 2; laboratory mouse; protein structure function; protein transport; tubulin; western blottings

DESCRIPTION (provided by applicant): We have data indicating that the interleukin-2 receptor (IL-2R) -beta, but not the alpha- or gamma-, chain is enriched in rafts and that it associates with cytoskeletal tubulin. These findings are in keeping with the growing recognition that both rafts and cytoskeletal proteins participate in and influence the function of various receptors on T cells. Further work, within an ongoing mentored training experience for the applicant, is thus proposed to test the hypothesis that the IL-2R beta-chain is critical for the interface of the IL-2R with rafts and the cytoskeleton and that this interface is functionally important. Standard molecular biological andmorphological techniques (e.g., immunoprecipitation and immunoblotting, internalization assays, confocal microscopy) will be used to address the following specific aims:1. Identification of mechanisms responsible for the raft-targeting of the IL-2R beta-chain;2. Further characterization of the dynamic relationship between the IL-2R beta-chain, rafts and the tubulin cytoskeleton;3. Investigation of the association of the IL-2/15R beta-chain with rafts and the cytoskeleton in antigen-specific T cells.The results derived from these studies characterizing the relationship between the IL-2R, especially its beta-chain, and rafts as well as the cytoskeleton will provide new insights into of cytokine receptor structure, function and turnover and thus provide for a more comprehensive understanding of processes critically involved in T cell function. The applicant's training towards becoming an independent scientist with a focus in transplantation immunology will be fostered in the process through continued mentoring by two established immunologists and participation in several didactic courses.

描述（由申请方提供）：我们有数据表明白细胞介素-2受体（IL-2 R）-β链（而非α链或γ链）在筏中富集，并且与细胞骨架微管蛋白相关。这些发现与越来越多的认识一致，即筏和细胞骨架蛋白都参与并影响T细胞上各种受体的功能。因此，在申请人正在进行的指导培训经验中，提出了进一步的工作来测试IL-2 R β链对于IL-2 R与筏和细胞骨架的界面是关键的并且该界面在功能上是重要的假设。标准分子生物学和形态学技术（例如，免疫沉淀和免疫印迹、内化测定、共聚焦显微镜）将用于解决以下具体目的：1.鉴定负责IL-2 R β链的筏靶向的机制;2.进一步表征IL-2 R β链、筏和微管蛋白细胞骨架之间的动态关系;3.研究IL-2/15 R β链与抗原特异性T细胞中筏和细胞骨架的关系，这些研究结果表征了IL-2 R，特别是其β链，与筏以及细胞骨架之间的关系，将为细胞因子受体结构提供新的见解，功能和营业额，从而提供了更全面的理解过程中关键参与T细胞功能。申请人的培训，成为一个独立的科学家，重点在移植免疫学将通过两个既定的免疫学家和参与几个教学课程的持续指导过程中培养。