FUNCTIONS, STRUCTURE, AND REGULATION OF RECEPTORS FOR CELL ADHESION PROTEINS

关键细胞外蛋白的受体，如纤维连接蛋白、胶原和 层粘连蛋白被认为在正常情况下介导黏附、迁移和侵袭。 或者是肿瘤细胞。整合素受体的功能和分布 用几种亚基特异性的单抗来研究这些分子。 抗体。研究发现，纤维连接蛋白受体α5β1起中心作用。 细胞黏附、细胞外基质组装和肌动蛋白的作用 细胞骨架组织。研究发现它与T细胞有协同作用 淋巴细胞增殖中的受体。β1整合素的其他成员 发现该家族参与了细胞-细胞和细胞-基质 相互作用，例如，在维持细胞接触和相邻 角质形成细胞中的细胞骨架组织。β1整合素的抑制作用 功能扰乱了几个系统中的纤维连接蛋白基质组装，以及 阻碍了胚胎发育中正常的原肠形成。生物合成和生物合成 整合素受体在某些肿瘤中的定位不同。 细胞。例如，Beta1亚基的成熟率为 在转化的人类细胞中加速，定位被扰乱 这些细胞和鳞状细胞癌中。另一种整合素受体 命名为alpha4beta1，它结合到 纤维连接蛋白是从转移性人黑色素瘤细胞中分离出来的。这个 整合素受体的分布反映并可能影响它们的 功能：当定位于粘连斑块时，它们似乎是 细胞外基质组装系统，并有助于延缓细胞迁移。 在快速迁移的胚胎细胞或某些肿瘤细胞中，它们可以 广泛地组织起来，更直接地参与细胞迁移。进一步 这几种整合素受体的调节和功能分析 胞外蛋白将为进一步深入了解 细胞黏附、迁移和侵袭，并应提供新的方法 更具体地说，就是抑制它们。

Receptors for key extracellular proteins such as fibronectin, collagen, and laminin are thought to mediate adherence, migration, and invasion by normal or tumor cells. The functions and distributions of integrin receptors for these molecules were explored using several subunit-specific monoclonal antibodies. The alpha5beta1 fibronectin receptor was found to play central roles in cell adhesion, extracellular matrix assembly, and actin cytoskeletal organization. It was found to synergize with the T-cell receptor in lymphocyte proliferation. Other members of the beta1 integrin family were found to be involved in cell-cell as well as cell-matrix interactions, e.g., in the maintenance of cell contacts and adjacent cytoskeletal organization in keratinocytes. Inhibition of beta1 integrin function disrupted fibronectin matrix assembly in several systems, and blocked normal gastrulation in embryonic development. Biosynthesis and localization of integrin receptors was found to differ in certain tumor cells. For example, the rate of maturation of beta1 subunits was accelerated in transformed human cells, and localization was disrupted in these cells and in squamous cell carcinomas. Another integrin receptor termed alpha4beta1, which binds to a cell-type specific sequence in fibronectin, was isolated from metastatic human melanoma cells. The distribution of integrin receptors reflects, and may also affect, their function: when localized to adhesion plaques, they appear to be part of an extracellular matrix assembly system and to help to retard cell migration. In rapidly migrating embryonic cells or certain tumor cells, they can be diffusely organized and more directly involved in cell migration. Further analyses of the regulation and function of these integrin receptors for extracellular proteins will provide further insights into the mechanisms of cell adhesion, migration, and invasion, and should provide novel approaches to inhibiting them more specifically.