INTERACTIONS OF GELATINASES WITH SERUM/MEMBRANE PROTEIN

肿瘤细胞的转移性扩散通常是癌症患者死亡的原因。 癌症患者。 更全面地了解分子 转移的机制是找到治愈任何形式的癌症的关键。 恶性肿瘤 明胶酶A和B直接参与转移。 的 酶在基底的溶解中起重要作用 膜等在入侵的初始阶段至关重要， 外渗。 这项建议的广泛的长期目标有两个方面。 一是 描述明胶酶之间的结合相互作用的意义 一方面是血清糖蛋白、去唾液酸胎球蛋白和胎球蛋白， 明胶酶和它们假定的膜受体。 其次，为了显示膜结合明胶酶是否执行其他功能， 管家的作用，除了溶解的基底膜。 具体的目的是：a）阐明两个中的结合结构域 B）评价脱唾液酸胎球蛋白和明胶酶的可溶性和 固定的脱唾液酸胎球蛋白/胎球蛋白和其它相关蛋白质， c）为了鉴定细胞膜受体， 并评估配体-受体相互作用，d）为了 分析明胶酶和31 kDa之间的细胞表面相互作用 人半乳糖苷结合蛋白（人半乳糖凝集素-3）。 放射性标记 冷的前明胶酶将与胎球蛋白/去唾液酸胎球蛋白一起孵育， 监测酶原的结合、切割和活化。 等离子体 膜受体也将被分离、纯化， 互动分析。 这些研究将提供关于 明胶酶在细胞表面和细胞膜中的活性 细胞内空间

The metastatic spread of tumor cells is usually the cause of death in cancer patients. A more complete understanding of the molecular mechanisms of metastasis is pivotal to finding a cure for any form of malignancy. Gelatinases A and B are directly involved in metastasis. The enzymes play a significant role in the dissolution of the basement membrane and so are critical in the initial stages of invasion and extravasation. The broad long-term objectives of this proposal is twofold. Firstly, to delineate the significance of the binding interactions between gelatinases and the serum glycoproteins, asialofetuin and fetuin on the one hand, and gelatinases and their putative membrane receptors on the other hand. Secondly, to show whether or not membrane bound gelatinases perform other housekeeping roles, apart from the dissolution of the basement membrane. The specific aims are: a) To elucidate the binding domains in both asialofetuin and gelatinases, b) To evaluate the ability of soluble and immobilized asialofetuin/fetuin and other related proteins in the activation of pro-gelatinases, c) To identify the cell membrane receptors for gelatinases and evaluate the ligand-receptor interactions, d) To analyze the cell surface interactions between gelatinases and the 31 kDa human galactoside binding protein (human galectin-3). Radioactive labeled and cold pro-gelatinases will be incubated with fetuin/asialofetuin and binding, cleavage, and activation of the zymogens monitored. The plasma membrane receptors will also be isolated, purified and the ligand-receptor interactions analyzed. Such studies will provide vital information on the activity of gelatinases on the cell surface as well as in the intracellular spaces.