Fazioli F, Resnati M, Sidenius N, Higashimoto Y, Appella E, Blasi F
Department of Biology and Biotechnology (DIBIT), San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy.
EMBO J. 1997 Dec 15;16(24):7279-86. doi: 10.1093/emboj/16.24.7279.
The role of urokinase-type plasminogen activator (uPA) and its receptor (uPAR/CD87) in cell migration and invasion is well substantiated. Recently, uPA has been shown to be essential in cell migration, since uPA-/- mice are greatly impaired in inflammatory cell recruitment. We have shown previously that the uPA-induced chemotaxis requires interaction with and modification of uPAR/CD87, which is the true chemoattracting molecule acting through an unidentified cell surface component which mediates this cell surface chemokine activity. By expressing and testing several uPAR/CD87 variants, we have located and functionally characterized a potent uPAR/CD87 epitope that mimics the effects of the uPA-uPAR interaction. The chemotactic activity lies in the region linking domains 1 and 2, the only protease-sensitive region of uPAR/CD87, efficiently cleaved by uPA at physiological concentrations. Synthetic peptides carrying this epitope promote chemotaxis and activate p56/p59(hck) tyrosine kinase. Both chemotaxis and kinase activation are pertussis toxin sensitive, involving a Gi/o protein in the pathway.
尿激酶型纤溶酶原激活剂（uPA）及其受体（uPAR/CD87）在细胞迁移和侵袭中的作用已得到充分证实。最近研究表明，uPA在细胞迁移中至关重要，因为uPA基因敲除小鼠的炎症细胞募集功能严重受损。我们之前已经证明，uPA诱导的趋化作用需要与uPAR/CD87相互作用并对其进行修饰，uPAR/CD87是通过一种未知的细胞表面成分发挥作用的真正趋化分子，该成分介导这种细胞表面趋化因子活性。通过表达和测试几种uPAR/CD87变体，我们定位并在功能上鉴定了一个有效的uPAR/CD87表位，其模拟了uPA-uPAR相互作用的效应。趋化活性位于连接结构域1和结构域2的区域，这是uPAR/CD87唯一对蛋白酶敏感的区域，在生理浓度下可被uPA有效切割。携带该表位的合成肽可促进趋化作用并激活p56/p59（hck）酪氨酸激酶。趋化作用和激酶激活均对百日咳毒素敏感，表明该途径涉及Gi/o蛋白。
