GALECTIN-1 INDUCES CELLULAR APOPTOSIS

描述(改编自调查人员的摘要)：细胞凋亡是一种 发育、形态发生和调控中的基本调控过程 对免疫系统的影响。尽管这一过程在两个基本领域都很重要 在发育计划和病理条件下，人们对此知之甚少 可以触发细胞凋亡的分子。我们的实验室最近进行了 证明了半乳糖-1，一种内源性碳水化合物结合蛋白， 可诱导人胸腺细胞和活化的T细胞的凋亡。半乳糖蛋白-1 是动物凝集素家族的一员，其同源物被表达 在从海绵和线虫到人类的物种中。在人类淋巴组织中， Galactin-1由胸腺、淋巴结(LN)和胸腺的基质细胞表达。 脾。Galactin-1与包括CD45在内的四种T细胞表面糖蛋白结合 以及CD43和CD45，这是一种酪氨酸磷酸酶，是半乳糖蛋白-1所必需的 诱导细胞凋亡。这项应用研究了半乳糖蛋白-1的作用机制 诱导T细胞凋亡，关注T细胞的结构特征 Galactin-1结合和信号转导所需的表面拮抗受体，以及 在Galactin-1信号通路的初始步骤上。具体目标 其用途是：1.表征低聚糖的性质 和T细胞表面对抗性受体的蛋白质成分 对于将Galactin-1信号转导至死亡非常重要。2.检查 Galactin-1结合后的对抗受体交联型式， 以及特定的细胞质分子是否与对抗受体相关联 在Galactin-1处理的细胞中。3.确定CD45区域的特征 半乳糖蛋白-1诱导的细胞凋亡所必需的磷酸酶结构域，以及 检测Galactin-1结合对细胞酪氨酸激酶的影响。这个 这个应用程序中的实验将有助于我们理解 不同的途径可以导致最终的凋亡终点，以及 还将提出新的方法来调节T细胞的增殖 病理过程，如自身免疫性疾病和淋巴系恶性肿瘤。

DESCRIPTION (Adapted from the Investigator's abstract): Apoptosis is a fundamental regulatory process in development, morphogenesis and in control of the immune system. Despite the importance of this process in both basic developmental programs and in pathologic conditions, little is known about the molecules which can trigger apoptosis. Our laboratory has recently demonstrated that galactin-1, an endogenous carbohydrate binding protein, can induce apoptosis of human thymocytes and activated T-cells. Galactin-1 is a member of a family of animal lectins, homologues of which are expressed in species from sponges and C. elegans to humans. In human lymphoid tissue, galactin-1 is expressed by stromal cells in thymus, lymph nodes (LN) and spleen. Galactin-1 binds four T-cell surface glycoproteins, including CD45 and CD43, and CD45, a tyrosine phosphatase, is required for galactin-1 induced apoptosis. This application examines the mechanism of galactin-1 induced T-cell apoptosis, focusing on the structural features of the T-cell surface counterreceptors required for galactin-1 binding and signaling, and on the initial steps in the galactin-1 signaling pathway. The specific aims of the application are: 1. To characterize features of the oligosaccharide and protein components of T-cell surface counterreceptors which are important for transducing the galactin-1 signal to die. 2. To examine the pattern of counterreceptor cross-linking subsequent to galactin-1 binding, and whether specific cytoplasmic molecules associate with counterreceptors in galactin-1 treated cells. 3. To characterize regions of the CD45 phosphatase domain essential for galactin-1 induced apoptosis, and to examine the effects of galactin-1 binding on cellular tyrosine kinases. The experiments in this application will contribute to our understanding of the different pathways which can lead to the final endpoint of apoptosis, and will also suggest novel approaches to modulating T-cell proliferation in pathologic processes such as autoimmune disease and lymphoid malignancies.