The Cytoskeleton, Rafts and the Interleukin-2 Receptor

描述(申请人提供)：我们有数据表明，白介素2受体(IL-2R)-β，而不是α-或伽马-，链在筏子中是丰富的，它与细胞骨架微管蛋白有关。这些发现与人们越来越多地认识到，筏子和细胞骨架蛋白都参与并影响T细胞上各种受体的功能是一致的。因此，在申请者正在进行的有指导的培训经验中，建议进行进一步的工作，以检验IL-2Rβ链对于IL-2R与筏子和细胞骨架的接口至关重要，并且这种接口在功能上是重要的这一假设。标准的分子生物学和形态学技术(如免疫沉淀和免疫印迹、内化分析、共聚焦显微镜)将被用来解决以下特定目标：1.识别IL-2Rβ链RAFT靶向的机制；2.进一步表征IL-2Rβ链、RAFT和微管蛋白细胞骨架之间的动态关系；3.研究IL-2/15Rβ链与RAFT和抗原特异性T细胞细胞骨架的关系。这些研究结果表明，IL-2R特别是其β链与RAFT和细胞骨架之间的关系将对细胞因子受体的结构、功能和周转提供新的见解，从而为更全面地了解T细胞功能中的关键过程提供了更全面的理解。申请人将通过两名知名免疫学家的持续指导和参加几门教学课程，在此过程中培养成为一名专注于移植免疫学的独立科学家的培训。

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.