STRUCTURAL ANALYSES AND FUNCTIONS OF RECEPTORS FOR CELL ADHESION PROTEINS

细胞通过特定的方式与细胞外基质分子相互作用 感受器。我们已经表征了膜结合分子 纤维粘连蛋白和胶原蛋白。纤维连接蛋白的分布 受体在转化后被破坏为弥漫性模式。 禽类细胞的。这种改变可以通过治疗 含有阻断受体的合成肽的正常细胞 功能，并可通过治疗 外源细胞纤维连接蛋白转化细胞。这 发现受体在发育过程中是必需的- 调控的侵袭事件，其中造血祖细胞 瞬间获得跨过基底膜的入侵能力 在体内和体外。一种相关的纤维连接蛋白受体，相当于 人类IC-IIa复合体是在血小板上发现的，它是 显示在血小板与纤维连接蛋白的黏附中起作用。关键角色 用于碳水化合物加工获取纤维连接蛋白 受体功能正在检测中。我们还进一步 鉴定了我们发现的一种主要的47K胶原结合蛋白 成为一种转变敏感的、新颖的热冲击调节器 糖蛋白，其磷酸化程度在 转型。免疫荧光和免疫电子 显微镜研究将其主要定位于内质 网状；在体内以细胞类型的特定模式表达。 它与胶原蛋白的结合受pH调节，释放最大 结合配体在pH为6.3的条件下。这一发现使它得以在 一种独特的N-末端36-氨基的天然形态和测定 序列。我们将进一步描述这种胶原蛋白和其他胶原蛋白- 结合蛋白，探索纤维连接蛋白和胶原的作用 细胞黏附、迁移和侵袭的受体。

Cells interact with extracellular matrix molecules by specific receptors. We have characterized membrane binding molecules for fibronectin and collagen. The distribution of fibronectin receptors was disrupted to a diffuse pattern after transformation of avian cells. This alteration could be mimicked by treatment of normal cells with a synthetic peptide that blocks receptor function, and it could be partially reverted by treatment of transformed cells with exogenous cellular fibronectin. This receptor was found to be required for a developmentally- regulated invasive event in which hemopoietic precursor cells transiently gain the ability to invade across basement membranes in vivo and in vitro. A related fibronectin receptor equivalent to the human Ic-IIa complex was discovered on platelets, and it was shown to function in platelet adherence to fibronectin. A key role for carbohydrate processing in the acquisition of fibronectin receptor function is being examined. We have also further characterized a major 47K collagen-binding protein that we found to be a transformation-sensitive, novel heat-shock regulated glycoprotein, whose phosphorylation was increased after transformation. Immunofluorescence and immunoelectron microscopic studies localized it primarily to the endoplasmic reticulum; it was expressed in cell-type specific patterns in vivo. Its binding to collagen was regulated by pH, with maximal release of bound ligand at pH 6.3. This finding permitted its isolation in native form and determination of a unique N-terminal 36-amino sequence. We will further characterize this and other collagen- binding proteins, exploring the role of fibronectin and collagen receptors in cell adhesion, migration, and invasion.