Wei Y, Waltz D A, Rao N, Drummond R J, Rosenberg S, Chapman H A
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
J Biol Chem. 1994 Dec 23;269(51):32380-8.
Urokinase receptors, expressed on surfaces of many cell types, focus to the pericellular space plasminogen-dependent proteolysis important in matrix remodeling and cell movement. We now report that the urokinase receptor (uPAR) is also a high affinity (Kd < 30 nM) receptor for vitronectin. Recombinant uPAR binds vitronectin in the absence of urokinase, but vitronectin binding is promoted by concurrent receptor binding of either urokinase or fragments thereof containing its uPAR binding domain. Stable epithelial cell transfectants expressing membrane-anchored uPAR, but not cells expressing soluble uPAR, become strongly adhesive with altered morphology in the absence of urokinase. These observations identify a new class of vitronectin receptor and imply a duality in function for the receptor that intrinsically links matrix adhesion to regulation of protease activity. Increases in urokinase receptor expression known to be associated with cellular activation and malignant transformation could modulate cellular trafficking and function by promoting attachment to vitronectin.
尿激酶受体表达于多种细胞类型的表面，在细胞周围空间聚焦纤溶酶原依赖性蛋白水解，这在基质重塑和细胞运动中很重要。我们现在报告，尿激酶受体（uPAR）也是玻连蛋白的高亲和力（Kd < 30 nM）受体。重组uPAR在没有尿激酶的情况下结合玻连蛋白，但尿激酶或其包含uPAR结合域的片段的同时受体结合可促进玻连蛋白结合。表达膜锚定uPAR的稳定上皮细胞转染子，而非表达可溶性uPAR的细胞，在没有尿激酶的情况下会变得具有强粘附性且形态改变。这些观察结果确定了一类新的玻连蛋白受体，并暗示该受体在功能上具有双重性，即内在地将基质粘附与蛋白酶活性调节联系起来。已知与细胞活化和恶性转化相关的尿激酶受体表达增加，可能通过促进与玻连蛋白的附着来调节细胞运输和功能。
