tailieunhanh - Báo cáo khoa học: Tetranectin binds hepatocyte growth factor and tissue-type plasminogen activator

In the search for new ligands for the plasminogen kringle 4 binding-protein tetranectin, it has been found by ligand blot analysis andELISAthat tetranectinspecificallybound to the plasminogen-like hepatocyte growth factor and tissue-type plasminogen dissociation constants of these complexes were found to be within the same order of mag-nitude as the one for the plasminogen-tetranectin complex. The study also revealed that tetranectin did not interact with the kindred proteins: macrophage-stimulating protein, urokinase-type plasminogen activator and prothrombin | Eur. J. Biochem. 270 1850-1854 2003 FEBS 2003 doi Tetranectin binds hepatocyte growth factor and tissue-type plasminogen activator Uffe B. Westergaard Mikkel H. Andersen Christian W. Heegaard Sergey N. Fedosov and Torben E. Petersen Protein Chemistry Laboratory Department of Molecular and Structural Biology University of Aarhus Denmark In the search for new ligands for the plasminogen kringle 4 binding-protein tetranectin it has been found by ligand blot analysis and ELISA that tetranectin specifically bound to the plasminogen-like hepatocyte growth factor and tissue-type plasminogen activator. The iis ccaiikm contlanls of these complexes were found to be within the same order of magnitude as the one for the plasminogen-tetranectin complex. The study also revealed that tetranectin did not interact with the kindred proteins macrophage-stimulating protein urokinase-type plasminogen activator and order to examine the function of tetranectin a kinetic analysis of the tPA-catalysed plasminogen activation was performed. Obe 1 00 parameters of the lelraneciin-stimulated enhancement of tPA were comparable to fibrinogen fragments which are so far the best inducer of tPA-catalysed plasminogen activation. The Olnchyed activation was suggested to be caused by tetranectin s ability to bind and accumulate tPA in an active conformation. Keywords tetranectin plasminogen hepatocyte growth factor tissue-type plasminogen activator. Tetranectin TN is a homotrimeric C-type lectin 1 . it was originally purified due to its specific affinity towards the kringle-4 domain of plasminogen Plg 2 . Each of the th 1 ee 20 kDa-monomers consists of an N-terminal heparin-binding domain an a-helical domain involved in the trimeriza-tion through a triple coiled coil structure and a C-terminal carbohydrate recognition domain responsible for the binding to Plg 3 4 . lntt latiCim between die cnroohydrnte recognition domain and Plg is both lysine and .