Waltz D A, Chapman H A
Department of Medicine, Harvard Medical School, Boston, Massachusetts.
J Biol Chem. 1994 May 20;269(20):14746-50.
Urokinase receptors are distributed on surfaces of many cell types where they are thought to focus plasminogen-dependent proteolysis important to migration and tissue remodeling to the immediate pericellular space. In addition to its well characterized role in proteolysis, urokinase receptor binding per se promotes the adhesiveness of leukemic cell lines exposed to differentiating cytokines in vitro. We sought to determine if a serum or matrix component is involved in urokinase-dependent adhesion. We now report that cytokine-stimulated human myelomonocytic cells express a divalent cation- and Arg-Gly-Asp-independent high affinity receptor for urea-purified vitronectin (Kd < 10 nM). Soluble native vitronectin does not effectively bind to the receptor, while cellular adhesion was noted to both urea-purified and native vitronectin when adsorbed to plastic. The activity of this receptor is tightly coupled to urokinase receptor occupancy. Urokinase receptor binding thus induces selective and reversible cellular adhesion to the matrix form of vitronectin. Because transfer of vitronectin-bound plasminogen activator inhibitor type 1 to urokinase promotes rapid turnover of receptor-bound enzyme, these results illuminate a novel binding cycle by which urokinase receptor occupancy coordinately regulates cellular adhesiveness and pericellular proteolysis.
尿激酶受体分布于多种细胞类型的表面，人们认为它们可将对迁移和组织重塑至关重要的纤溶酶原依赖性蛋白水解作用集中于紧邻细胞周围的空间。除了其在蛋白水解方面已得到充分表征的作用外，尿激酶受体本身的结合还能促进体外暴露于分化细胞因子的白血病细胞系的黏附性。我们试图确定血清或基质成分是否参与尿激酶依赖性黏附。我们现在报告，细胞因子刺激的人骨髓单核细胞表达一种对尿素纯化的玻连蛋白具有二价阳离子和精氨酸 - 甘氨酸 - 天冬氨酸非依赖性的高亲和力受体（解离常数<10 nM）。可溶性天然玻连蛋白不能有效地与该受体结合，而当吸附到塑料上时，尿素纯化的玻连蛋白和天然玻连蛋白均能引起细胞黏附。该受体的活性与尿激酶受体的占据紧密相关。因此，尿激酶受体的结合诱导细胞对玻连蛋白基质形式进行选择性和可逆性黏附。由于结合在玻连蛋白上的1型纤溶酶原激活物抑制剂向尿激酶的转移促进了受体结合酶的快速周转，这些结果揭示了一个新的结合循环，通过该循环尿激酶受体的占据协同调节细胞黏附性和细胞周围蛋白水解作用。
