A Novel Cell Death Pathway Induced by Galectin-1

Galectin-1 诱导的新型细胞死亡途径

基本信息

批准号：
6753612
负责人：
Linda G Baum
金额：
$ 25.86万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-09-01 至 2005-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6753612
关键词：
CD antigens T cell receptor T lymphocyte apoptosis biological signal transduction cell death confocal scanning microscopy cytoskeletal proteins genetically modified animals laboratory mouse lectin phosphoprotein phosphatase protein kinase C receptor binding thymus

项目摘要

DESCRIPTION (provided by applicant): Cell death is a critical regulatory process in development, in homeostasis, and in disease. Many cell death triggers have been identified, although little is known about many of the molecular pathways that lead to cell death. Galectin-1, a member of a family of evolutionarily ancient lectins, induces death of thymocytes and T-cells. In mammals, galectin-1 is expressed in lymphoid tissues, at sites of inflammation, and in some types of cancer. Galectin-1 has also been shown to be immunosuppressive in several animal models of autoimmune disease. Galectin-1 induces cell death of transformed epithelial cells as well, so that galectin-1 mediated cell death may be a fundamental mechanism that regulates cell survival in many tissues. Other galectin family members have pro- or anti-apoptotic activities in different tissues, suggesting that different galectins may cooperate to regulate cell death. The goal of this application is to characterize the molecular mechanism of galectin-1 cell death, to understand the interaction of galectin-1 with glycoprotein receptors on the cell surface, and the downstream events that regulate cell death. The Specific Aims are: 1. To define features of the T-cell surface receptors for galectin-l required to transmit the death signal. CD7 and CD43 are glycoprotein receptors for galectin-1. Features of the glycans and the polypeptides that are essential for sending the death signal will be identified. 2. To examine how galectin-l binding to T-cells results in molecular interactions to deliver the death signal. Galectin-1 binding results in a unique pattern of receptor reorganization on the T-cell surface. We will identify features of the receptors required for this interaction, and investigate whether receptor reorganization is required for cell death. Effects of galectin-1 on cytoskeletal linker proteins and on the actin cytoskeleton will be characterized. To examine cell-cell interactions that govern T-cell death, receptor reorganization during galectin-1 mediated binding of T-cells to thymic stromal cells will be examined. 3. To characterize intracellular components that regulate the galectin-l cell death pathway. We will examine the roles of the protein kinase C and protein phosphatase families of enzymes in regulating galectin1 cell death. We determine how galectin-3 expression regulates T-cell susceptibility to galectin-1.

描述（由申请人提供）：细胞死亡是关键的调节发展过程中的过程，体内平衡和疾病。许多细胞死亡已经确定了触发器，尽管对许多导致细胞死亡的分子途径。 Galectin-1，一个家庭的成员进化上古老的凝集素，诱导胸腺细胞和T细胞死亡。在哺乳动物，lectectin-1在淋巴组织中表达，在炎症部位，在某些类型的癌症中。 Galectin-1也已显示为在几种自身免疫性疾病的动物模型中免疫抑制。 Galectin-1 也诱导转化的上皮细胞的细胞死亡，因此galectin-1 介导的细胞死亡可能是调节细胞存活的基本机制在许多组织中。其他血肠蛋白家庭成员有促凋亡或抗凋亡不同组织中的活性，表明不同的甲状腺可能合作调节细胞死亡。该应用的目的是表征半乳糖素-1细胞死亡的分子机制，以了解 lectectin-1与细胞表面上的糖蛋白受体的相互作用，以及调节细胞死亡的下游事件。具体目的是： 1。为lectectin-l定义T细胞表面受体的特征传输死亡信号。 CD7和CD43是糖蛋白受体的 Galectin-1。糖和多肽的特征是必不可少的发送死亡信号将被识别。 2。检查乳肠蛋白L与T细胞的结合如何导致分子交互以传达死亡信号。 Galectin-1结合导致A T细胞表面上受体重组的独特模式。我们将确定这种相互作用所需的受体的特征，并研究细胞死亡是否需要受体重组。效果 galectin-1在细胞骨架接头蛋白上和肌动蛋白细胞骨架上的将被描述。检查控制T细胞的细胞细胞相互作用死亡，Galectin-1期间的受体重组T细胞与T细胞的结合将检查胸腺基质细胞。 3。表征调节半乳肠蛋白L细胞的细胞内成分死亡道路。我们将检查蛋白激酶C和蛋白质磷酸酶的作用酶的家族调节galectin1细胞死亡。我们确定如何 Galectin-3表达调节T细胞对lectectin-1的敏感性。