TGF BETA RECEPTOR DYNAMICS

TGFβ受体动力学

• 批准号: 6180737
• 负责人: EDWARD B LEOF
• 金额: $ 22.74万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6180737
• 关键词: clathrin; endocytosis; enzyme activity; growth factor receptors; intermolecular interaction; intracellular transport; laboratory rabbit; protein degradation; protein kinase; protein transport; receptor binding; receptor coupling; receptor expression; tissue /cell culture; transforming growth factors

DESCRIPTION: The hypothesis to be investigated is that distinct elements within the cytoplasmic and/or transmembrane domain(s) of the type 1 and type 2 TGF-beta heteromeric receptors mediate heteromeric receptor association with clathrin coated pit proteins and receptor downregulation. Since the homomeric type 1 or type 2 receptors can be internalized but are not down-regulated and cannot signal, it is further hypothesized that there is ligand dependent crosstalk between the heteromeric partners. A chimeric TGF-beta receptor model will be used for the proposed studies: murine AKR-2B mesenchymal (fibroblast) cell clones expressing chimeric TGF-beta receptors consisting of the extracellular ligand binding domain of the GM-CSF alpha or beta receptors fused with the transmembrane and cytoplasmic domain of the type 1 or type 2 TGF-beta receptors. This chimeric model system permits investigation of the signaling capacity of TGF-beta receptor type 1/type 1 homomers, type 2/type 2 homomers and type1/type 2 heteromers. The specific aims are: 1. identification and characterization of the receptor elements mediating downregulation of heteromeric type 1/type 2 receptor complexes; 2. determination how TGF-beta receptors are sorted following association with the clathrin lattice; 3. determination whether TGF-beta receptor kinase activity or phosphorylation modulates receptor trafficking.

描述：要研究的假设是不同的元素 在类型1和类型的细胞质和/或跨膜结构域中 2 TGF-β杂体受体介导异源受体关联 与网状蛋白涂层的坑蛋白和受体下调。 自从 同源1型或2型受体可以内部化，但不是 下调且无法发出信号，进一步假设存在 异形伙伴之间的配体依赖性串扰。 嵌合 TGF-β受体模型将用于拟议的研究：鼠 AKR-2B间充质（成纤维细胞）细胞克隆表达嵌合TGF-beta 由细胞外配体结合结构域组成的受体 与跨膜和细胞质融合的GM-CSFα或β受体 1型或2型TGF-β受体的域。 这个嵌合模型 系统允许研究TGF-β受体的信号传导能力 类型1/类型1同源物，类型2/类型2同源物和类型1/类型2个异构体。 具体目的是：1。识别和表征 介导杂体1/2型下调的受体元件 受体复合物； 2。确定如何分类TGF-β受体 在与氯酸链蛋白晶格的关联之后； 3。确定是否 TGF-β受体激酶活性或磷酸化调节受体 贩运。