NR ASRW
AU West,D.C.; Rees,C.G.; Duchesne,L.; Patey,S.J.; Terry,C.J.; Turnbull,J.E.; Delehedde,M.; Heegaard,C.W.; Allain,F.; Vanpouille,C.; Ron,D.; Fernig,D.G.
TI Interactions of multiple heparin binding growth factors with neuropilin-1 and potentiation of the activity of fibroblast growth factor-2
QU The Journal of Biological Chemistry 2005 Apr 8; 280(14): 13457-64
PT journal article
AB The hypothesis that neuropilin-1 (Npn-1) may interact with heparin-binding proteins other than vascular endothelial growth factor has been tested using an optical biosensor-based binding assay. The results show that fibroblast growth factor (FGF) 1, 2, 4, and 7, FGF receptor 1, hepatocyte growth factor/scatter factor (HGF/SF), FGF-binding protein, normal protease sensitive form of prion protein, antithrombin III, and Npn-1 itself are all able to interact with Npn-1 immobilized on the sensor surface. FGF-2, FGF-4, and HGF/SF are also shown to interact with Npn-1 in a solution assay. Moreover, these protein-protein interactions are dependent on the ionic strength of the medium and are inhibited by heparin, and the kinetics of binding of FGF-2, FGF-4 and HGF/SF to Npn-1 are characterized by fast association rate constants (270,000-1,600,000 m(-1) s(-1)). These results suggest that Npn-1 possesses a "heparin" mimetic site that is able to interact at least in part through ionic bonding with the heparin binding site on many of the proteins studied. Npn-1 was also found to potentiate the growth stimulatory activity of FGF-2 on human umbilical vein endothelial cells, indicating that Npn-1 may not just bind but also regulate the activity of heparin-binding proteins.
MH Animals; Binding Sites; Biosensing Techniques; Cell Line; Endothelial Cells/cytology/metabolism; Fibroblast Growth Factor 2/*metabolism; Heparin/*metabolism; Hepatocyte Growth Factor/*metabolism; Humans; Models, Molecular; Neuropilin-1/chemistry/*metabolism; Polysaccharides/metabolism; Protein Isoforms/metabolism; Protein Structure, Tertiary; Receptor Protein-Tyrosine Kinases/metabolism; Receptors, Fibroblast Growth Factor/metabolism; Research Support, Non-U.S. Gov't
AD School of Biological Sciences, Biosciences Building, University of Liverpool, Liverpool, L69 7ZB, United Kingdom.
SP englisch
PO USA