Chemotactic effect of urokinase plasminogen activator: A major role for mechanisms independent of its proteolytic or growth factor domains

作     者：Poliakov, AA Mukhina, SA Traktouev, DO Bibilashvily, RS Gursky, YG Minashkin, MM Stepanova, VV Tkachuk, VA 

作者机构：Moscow State Univ Sch Basic Med Dept Biol & Med Chem Moscow 119899 Russia Cardiol Res Ctr Inst Expt Cardiol Moscow 121552 Russia 

出 版 物：《JOURNAL OF RECEPTOR AND SIGNAL TRANSDUCTION RESEARCH》 (受体与信号转导杂志)

年 卷 期：1999年第19卷第6期

页      面：939-951页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 09[农学] 

基　　金：Swiss Cardiology Society Russian Foundation for Fundamental Investigations, RFFI, (96-04-507 14) Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, SNF 

主　　题：结合部位/遗传学 结合 竞争性 细胞运动/药物作用 细胞 培养的 趋化作用/药物作用 肌 平滑 血管/药物作用 肌 平滑 血管/病理学 突变 受体 细胞表面/代谢 重组蛋白质类/化学 重组蛋白质类/遗传学 重组蛋白质类/药理学 尿纤溶酶原激活物/化学 尿纤溶酶原激活物/遗传学 尿纤溶酶原激活物/药理学 动物 大鼠 

摘      要：Urokinase type plasminogen activator (uPA) converts plasminogen to plasmin and is highly chemotactic for many cell types. We examined, using recombinant wild type and mutated forms of uPA, the extent to which its proteolytic properties, its growth-like domain (GFD) and/or interactions with the specific receptor (uPAR) contribute to the chemotactic activity towards vascular smooth muscle cells (SMC). Recombinant wild type uPA (r-uPA) stimulated cell migration nearly 5.8-fold, inactive r-uPA, with a mutation in the catalitic domain (r-uPA(H/Q)), 3-fold, uPA without growth factor like domain (r-uPA(GFD(-))), 2.6-fold, and a form containing both mutations (r-uPA(H/Q, GFD(-)), 3.3-fold. All recombinant forms of uPA, wild type and those with mutations were equally and highly effective (IC(50)similar to 20 nM) in displacing I-125-r-uPA bound to SMC. These results indicate that additional mechanisms, not dependent on uPA s proteolytic activity or the binding ability of its GFD to uPAR, are the major contributors to its chemotactic action on SMC.