Identification of the urokinase receptor as an adhesion receptor for vitronectin.

Identification of the urokinase receptor as an adhesion receptor for vitronectin.
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DOI:
10.1016/s0021-9258(18)31646-6
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发表时间:
1994-12
期刊:
The Journal of biological chemistry
影响因子:
--
通讯作者:
Ying‐Ying Wei;David A. Waltz;N. K. Rao;R. Drummond;S. Rosenberg;H. Chapman
Ying‐Ying Wei;David A. Waltz;N. K. Rao;R. Drummond;S. Rosenberg;H. Chapman
中科院分区:
其他
文献类型:
--
作者:
Ying‐Ying Wei;David A. Waltz;N. K. Rao;R. Drummond;S. Rosenberg;H. Chapman

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尿激酶受体在许多细胞类型的表面表达,专注于细胞周间隙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。我们现在报道尿激酶受体(uPAR)也是玻连蛋白的高亲和力(Kd < 30 nM)受体。重组uPAR在不存在尿激酶的情况下结合玻连蛋白,但尿激酶或其包含其uPAR结合结构域的片段的同时受体结合可促进玻连蛋白结合。在没有尿激酶的情况下,表达膜锚定 uPAR 的稳定上皮细胞转染子(而不是表达可溶性 uPAR 的细胞)变得与改变的形态强烈粘附。这些观察结果确定了一类新的玻连蛋白受体,并暗示该受体的功能具有双重性,其本质上将基质粘附与蛋白酶活性的调节联系起来。已知与细胞活化和恶性转化相关的尿激酶受体表达的增加可以通过促进与玻连蛋白的附着来调节细胞运输和功能。
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.