The Cytoskeleton, Rafts and the Interleukin-2 Receptor

细胞骨架、筏和 IL-2 受体

• 批准号: 6901839
• 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/6901839
• 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（由申请人提供）：我们有数据表明，白细胞介素-2受体(IL-2R) - β，而不是α或γ -链在筏中富集，并且它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，在对申请人进行的持续指导培训经验中，建议进一步的工作来验证IL-2R β链对于IL-2R与筏和细胞骨架的界面至关重要，并且该界面在功能上很重要的假设。标准的分子生物学和形态学技术（例如，免疫沉淀和免疫印迹，内化分析，共聚焦显微镜）将用于解决以下具体目标：1 .确定IL-2R β链筏靶的机制；2 .进一步表征IL-2R β链、筏和微管蛋白细胞骨架之间的动态关系；抗原特异性T细胞中IL-2/15R β链与筏和细胞骨架的关联研究。这些研究结果描述了IL-2R，特别是它的β链，和筏以及细胞骨架之间的关系，将为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细胞功能的关键过程提供帮助。申请人将通过两位免疫学家的持续指导和参加几门教学课程，培养成为一名专注于移植免疫学的独立科学家。

项目成果

Engagement of the CD4 receptor affects the redistribution of Lck to the immunological synapse in primary T cells: implications for T-cell activation during human immunodeficiency virus type 1 infection.

CD4 受体的参与影响 Lck 到原代 T 细胞免疫突触的重新分配：对人类免疫缺陷病毒 1 型感染期间 T 细胞激活的影响。

• DOI: 10.1128/jvi.01023-08
• 发表时间: 2009
• 期刊: Journal of virology
• 影响因子: 5.4
• 作者: Nyakeriga,AliceM;Fichtenbaum,CarlJ;Goebel,Jens;Nicolaou,StellaA;Conforti,Laura;Chougnet,ClaireA
• 通讯作者: Chougnet,ClaireA

Tubulin polymerization modulates interleukin-2 receptor signal transduction in human T cells.

微管蛋白聚合调节人 T 细胞中的 IL-2 受体信号转导。

• DOI: 10.1080/10799890600567372
• 发表时间: 2006
• 期刊: Journal of receptor and signal transduction research.
• 作者: Goebel,Jens;Forrest,Kathy;Wills-Karp,Marsha;Roszman,ThomasL
• 通讯作者: Roszman,ThomasL