TGF BETA RECEPTOR DYNAMICS

描述：要调查的假设是不同的元素 在1型和1型的细胞质和/或跨膜结构域(S)内 2转化生长因子-β异构体受体介导的异构体受体关联 与笼状蛋白包被的PIT蛋白和受体下调。自.以来 同源的1型或2型受体可以内化，但不能 下调并且不能发出信号，则进一步假设存在 异构体伙伴之间的配体依赖的串扰。一个嵌合者 转化生长因子-β受体模型将用于拟议的研究：小鼠 表达嵌合转化生长因子-β的AKR-2B间充质(成纤维)细胞克隆 由细胞外配体结合域组成的受体 GM-CSFα或β受体与跨膜和胞浆融合 1型或2型转化生长因子-β受体的结构域。这种嵌合式模型 系统允许研究转化生长因子-β受体的信号传递能力 类型1/类型1同聚体、类型2/类型2同聚体和类型1/类型2异构体。 具体目标是：1.识别和表征 介导异构体1/2下调的受体元件 受体复合体；2.确定转化生长因子-β受体的分类 在与笼状蛋白晶格结合之后；3.确定 转化生长因子-β受体激酶活性或磷酸化调节受体 贩卖人口。

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.