PREDOCTORAL FELLOWSHIPS FOR STUDENTS WITH DISABILITIES

为残疾学生提供博士前奖学金

• 批准号: 7176225
• 负责人: JAMES T TRBOVICH
• 金额: $ 2.72万
• 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 2009-10-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7176225
• 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; Fellowship; Fingers; Growth Factor; Homeostasis; Human; In Vitro; Individual; Inhibin-beta Subunits; Label; Ligand Binding; Ligands; Link; Maps; Measures; Methods; Multinuclear NMR; Multiple Myeloma; Names; Numbers; 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

DESCRIPTION (provided by applicant): In humans, the 42 polypeptides of the transforming growth factor beta (TGFB) 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 TGFB 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 TGFB-like ligands (such as those specific for TGFB, 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 TGFB, 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 cooperative 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 TGFB family by defining what is likely to be one of a limited number of assembly modes.

描述（由申请人提供）：在人类中，转化生长因子β（TGFB）家族的42种多肽控制多种细胞反应。它们在维持正常的细胞稳态，包括正常的肿瘤抑制中起重要作用，并且它们在发育中起关键作用。在过去的十年中，大量的努力已经指向了解TGFB信号传导，导致有关调节这一过程的机制的重要见解。当生长因子配体与细胞表面上的I型和II型信号传导受体结合时，信号传导过程被诱导。在人类细胞中鉴定的各种I型和II型受体，其中分别有7种和5种，已显示对TGF β样配体亚组（如对TGF β、激活素或BMP特异的那些）表现出广泛的特异性。然而，实现特异性的总体机制和控制特异性的决定因素尚未确定。迄今为止，用TGFB、激活素和BMP系统进行的结构研究揭示了意外的观察结果，即特异性不是通过单独的配体-受体接触的变化实现的，而是也通过整体组装模式的变化实现的。该提议的具体目标是定义配体的激活素亚组诱导激活素Ib型和激活素II型受体的协同组装的总体机制。从这些研究中出现的结果将补充我们的整体理解如何实现配体受体特异性在TGFB家庭定义什么是可能是有限数量的组装模式之一。