Camani C, Kruithof E K
Division of Hematology, University Hospital, Lausanne, Switzerland.
J Biol Chem. 1995 Nov 3;270(44):26053-6. doi: 10.1074/jbc.270.44.26053.
The relative contribution of the finger/growth factor domains of tissue-type plasminogen activator (t-PA) and of the other t-PA domains to the clearance of t-PA by hepatocytes was investigated. A recombinant finger/growth factor construct inhibited t-PA and t-PA/plasminogen activator inhibitor type-1 degradation with an IC50 of 1800 nM, whereas a t-PA mutant lacking the finger and growth factor domains inhibited degradation with an estimated IC50 of 1200 nM. In comparison the IC50 of t-PA was found to be approximately 10 nM. Clearance of t-PA by human or rat hepatoma cells was not inhibited by high concentrations of fucose (50 mM), which suggests that the fucose on Thr-61 is not involved in clearance by these cells. These results suggest that the binding of t-PA involves several low affinity binding sites located on distinct domains of the t-PA molecule.
研究了组织型纤溶酶原激活剂（t-PA）的指状/生长因子结构域以及其他t-PA结构域对肝细胞清除t-PA的相对贡献。一种重组指状/生长因子构建体抑制t-PA和t-PA/纤溶酶原激活剂抑制剂1型的降解，IC50为1800 nM，而缺乏指状和生长因子结构域的t-PA突变体抑制降解，估计IC50为1200 nM。相比之下，t-PA的IC50约为10 nM。高浓度岩藻糖（50 mM）不抑制人或大鼠肝癌细胞对t-PA的清除，这表明苏氨酸-61上的岩藻糖不参与这些细胞的清除。这些结果表明，t-PA的结合涉及位于t-PA分子不同结构域上的几个低亲和力结合位点。
