GALECTIN-1 INDUCES CELLULAR APOPTOSIS

描述（改编自研究者摘要）：细胞凋亡是一种 发育、形态发生和控制的基本调节过程 免疫系统。 尽管这一过程在两个基本的 发育程序和病理条件下，很少有人知道 引发细胞凋亡的分子 我们的实验室最近 证明了半乳糖凝集素-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T细胞凋亡。 半乳糖蛋白-1 是动物凝集素家族的一员，其同系物表达于 海绵和C. elegans to humans人类. 在人类淋巴组织中， galactin-1由胸腺、淋巴结（LN）和淋巴结中的基质细胞表达， 脾脏 Galactin-1结合四种T细胞表面糖蛋白，包括CD 45 和CD 43，和CD 45，一种酪氨酸磷酸酶，是半乳糖肌动蛋白-1所必需的 诱导凋亡。 本申请研究半乳糖凝集素-1的机制 诱导T细胞凋亡，重点是T细胞的结构特征， 半乳糖凝集素-1结合和信号传导所需的表面反受体，和 半乳糖凝集素-1信号通路的初始步骤。 具体目标 的应用是：1. 表征寡糖的特征 和T细胞表面反受体的蛋白质成分， 这对于将galactin-1信号转导至死亡很重要。 2. 审查 半乳糖凝集素-1结合后的反受体交联模式， 以及特定的细胞质分子是否与反受体结合 在半乳糖肌动蛋白-1处理的细胞中。 3. 表征CD 45的区域 半乳糖肌动蛋白-1诱导的细胞凋亡所必需的磷酸酶结构域， 检查半乳糖凝集素-1结合对细胞酪氨酸激酶的影响。 的 在这个应用中的实验将有助于我们理解 可以导致凋亡的最终终点的不同途径，以及 还将提出新的方法来调节T细胞增殖， 病理过程如自身免疫性疾病和淋巴恶性肿瘤。

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.