PREDOCTORAL FELLOWSHIPS FOR STUDENTS WITH DISABILITIES

为残疾学生提供博士前奖学金

• 批准号: 7983170
• 负责人: JAMES T TRBOVICH
• 金额: $ 2.74万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-02 至 2010-10-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7983170
• 关键词: 3-Dimensional; Activins; Apoptosis; Binding; Carcinoma; Cell Proliferation; Cell physiology; Cell surface; Cells; Chemicals; Complement; Complex; Development; Electrophoretic Mobility Shift Assay; Enzyme-Linked Immunosorbent Assay; Exhibits; Extracellular Domain; Family; Growth Factor; Homeostasis; Human; In Vitro; Label; Ligand Binding; Ligands; Link; Maps; Measures; Methods; Multinuclear NMR; Multiple Myeloma; Organism; Pituitary Hormones; Play; Predoctoral Fellowship--Students with Disabilities; Process; Receptor Signaling; Residual state; Role; Running; Sampling; Series; Signal Pathway; Signal Transduction; Solutions; Specificity; Structural Models; Structure; Subgroup; Surface; System; Tissues; Transforming Growth Factor beta; Tumor Suppression; Type II Activin Receptors; Variant; Vertebral column; cancer type; cell growth; computerized data processing; insight; member; polypeptide; receptor; receptor binding; research study; response

In humans, the 42 polypeptides of the transforming growth factor beta (TGFp) family control a wide variety of cellular responses. They play important roles in maintaining normal cellular homeostasis, including normal tumor suppression, and they play key roles in development. Over the last decade, significant effort has been directed toward understanding TGFp signaling, leading to significant insights regarding mechanisms that regulate this process. The signaling process is induced when the growth factor ligands bind to type I and type II signaling receptors on the cell surface. The various type I and type II receptors identified in human cells, of which there are seven and five, respectively, have been shown to exhibit broad specificity for subgroups of TGFp-like ligands (such as those specific for TGFp, activin, or BMPs). The overall mechanisms by which specificity is achieved and the determinants that govern specificity however have not been defined. Structural studies conducted thus far with the TGFp, activin, and BMP systems have revealed the unexpected observation that specificity is achieved not through variation in ligand-receptor contacts alone, but through variation in the overall assembly mode as well. The specific objective of this proposal is to define the overall mechanism by which the activin subgroup of ligands induces the coopera tive assembly of the activin type Ib and activin type II receptors. The findings that emerge from these studies will complement our overall understanding of how ligand-receptor specificity is achieved in the TGFp family by defining what is likely to be one of a limited number of assembly modes.

在人类中，转化生长因子β (TGFp) 家族的 42 种多肽控制着多种 细胞反应。它们在维持正常的细胞稳态中发挥着重要作用，包括正常的 肿瘤抑制，并且它们在发育中发挥关键作用。在过去的十年里，我们做出了巨大的努力 旨在了解 TGFp 信号传导，从而对以下机制产生重要见解 规范这个过程。当生长因子配体与 I 型和 I 型结合时，信号传导过程就会被诱导。 细胞表面的 II 型信号受体。人类体内鉴定出的各种 I 型和 II 型受体 细胞，其中分别有七个和五个，已被证明表现出广泛的特异性 TGFβ 样配体亚组（例如 TGFβ、激活素或 BMP 特异性的配体）。整体 然而，实现特异性的机制以及控制特异性的决定因素还没有 被定义。迄今为止对 TGFp、激活素和 BMP 系统进行的结构研究表明 意想不到的观察结果是特异性不是通过配体-受体接触的变化来实现的 单独地，但也通过整体组装模式的变化。该提案的具体目标是 定义配体的激活素亚组诱导协同组装的总体机制 Ib 型激活素和 II 型激活素受体。这些研究的结果将 补充我们对 TGFp 家族中配体受体特异性如何实现的整体理解 定义可能是有限数量的装配模式之一。