CHARACTERIZATION OF THE ELASTIN/LAMININ RECEPTOR

细胞表面的特化分子 从细胞外到细胞内的信息传递 隔间 这些分子中的大多数是受体， 可溶性刺激物，如激素和生长因子，而其他 分子与固定在另一个分子上的成分相互作用， 细胞或细胞外基质，并用于介导细胞 粘附或细胞运动。 总之，这些不同类型的 相互作用对许多过程的增长、发展和 修复损伤。 因此，受体的鉴定 参与细胞与细胞和细胞与基质的相互作用， 细胞生物学的重要目标。 我们最近的研究集中在识别和 结合弹性蛋白和弹性蛋白的细胞表面受体的表征 和层粘连蛋白，并在基质组装和细胞 迁移 弹性蛋白产生细胞上的这种受体是一种复合物， 三种蛋白质：61和55 kDa的两个跨膜亚基 具有与细胞骨架相互作用的胞质结构域， 和结合67 kDa亚基的细胞外结构域。 的67 kDa组分含有一个蛋白质结合位点， 半乳糖苷糖，和结合一种或两种糖的细胞结合位点 跨膜亚基的结构。 本提案的总体目标是更好地描述 这个受体的结构和功能。 具体目标 是纯化和表征受体亚基， 确定受体复合物在基质中的作用 组装件. 我们还希望确定 受体在调节细胞表型中的作用。 另一个目标是 为了更好地确定层粘连蛋白和弹性蛋白中的氨基酸序列， 受体识别，并确定如何改变 氨基酸序列改变受体-配体结合。 最后我们 计划开发弹性蛋白/层粘连蛋白受体的分子克隆 复合体及其基因。

Specialized molecules on the surface of cells serve to mediate information transfer from the extracellular to the intracellular compartments. Most of these molecules are receptors that bind soluble stimuli such as hormones and growth factors, whereas others are molecules that interact with components fixed either to other cells or to extracellular matricides and serve to mediate cell adhesion or cell movement. Together, these various types of interactions are critical to many processes growth, development and repair of injury. Therefore, the identification of receptors involved in cell-cell and cell-matrix interactions has become an important goal of cell biology. Our recent studies have focused on the identification and characterization of a cell surface receptor that binds both elastin and laminin, and plays a role in matrix assembly and cell migration. This receptor on elastin-producing cells is a complex of three proteins: two transmembrane subunits of 61 and 55 kDa with a cytoplasmic domain(s) that interacts with the cytoskeleton, and an extracellular domain that binds a 67 kDa subunit. The 67 kDa component contains a protein binding site that recognizes galactoside sugars, and a cell binding site that binds one or both of the transmembrane subunits. The overall objective of this proposal is to characterize better the structure and function of this receptor. The specific aims are to purify and characterize the receptor subunits and to ascertain the role played by the receptor complex in matrix assembly. We also wish to identify possible functions of the receptor in regulating cellular phenotypes. A further aim will be to better define the amino acid sequences in laminin and elastin recognized by the receptor, and determine how alterations in the amino acid sequences alter receptor-ligand binding. Finally, we plan to develop molecular clones of the elastin/laminin receptor complex and its genes.