PREDOCTORAL FELLOWSHIPS FOR STUDENTS WITH DISABILITIES

为残疾学生提供博士前奖学金

基本信息

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
项目类别：
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

项目摘要

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个多肽控制着各种各样的细胞反应。它们在维持正常的细胞稳态（包括正常肿瘤抑制）中起着重要作用，并且在发育中起关键作用。在过去的十年中，已经致力于理解TGFB信号传导，从而导致有关调节该过程的机制的重大见解。当生长因子配体与细胞表面上的I型和II型信号受体结合时，会诱导信号传导过程。在人类细胞中鉴定出的各种I型和II型受体，其中分别有七个和五种受体对TGFB样配体的亚组（例如TGFB，Activin或BMPS）具有广泛的特异性。但是，尚未定义实现特异性的总体机制和控制特异性的决定因素。到目前为止，使用TGFB，Activin和BMP系统进行的结构研究表明，意外的观察结果是，特异性不是仅通过单独的配体受体接触而而是通过整体组装模式中的变化来实现的。该提案的具体目标是定义总体机制，通过该机制，配体的活化素亚组诱导了激活素型IB和AIVIVIN II型受体的合作组装。从这些研究中出现的发现将通过定义可能是有限数量的组装模式之一来补充我们对TGFB家族中配体受体特异性的总体理解。