PMID- 15695515 OWN - NLM STAT- MEDLINE DCOM- 20050621 LR - 20210206 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 280 IP - 14 DP - 2005 Apr 8 TI - Interactions of multiple heparin binding growth factors with neuropilin-1 and potentiation of the activity of fibroblast growth factor-2. PG - 13457-64 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. FAU - West, David C AU - West DC AD - School of Biological Sciences, Biosciences Building, University of Liverpool, Liverpool, L69 7ZB, United Kingdom. FAU - Rees, Chris G AU - Rees CG FAU - Duchesne, Laurence AU - Duchesne L FAU - Patey, Susannah J AU - Patey SJ FAU - Terry, Carla J AU - Terry CJ FAU - Turnbull, Jeremy E AU - Turnbull JE FAU - Delehedde, Maryse AU - Delehedde M FAU - Heegaard, Christian W AU - Heegaard CW FAU - Allain, Fabrice AU - Allain F FAU - Vanpouille, Christophe AU - Vanpouille C FAU - Ron, Dina AU - Ron D FAU - Fernig, David G AU - Fernig DG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20050204 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Polysaccharides) RN - 0 (Protein Isoforms) RN - 0 (Receptors, Fibroblast Growth Factor) RN - 103107-01-3 (Fibroblast Growth Factor 2) RN - 144713-63-3 (Neuropilin-1) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - 9005-49-6 (Heparin) RN - EC 2.7.10.1 (FGFR1 protein, human) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 1) SB - IM MH - Animals MH - Binding Sites MH - Biosensing Techniques MH - Cell Line MH - Endothelial Cells/cytology/metabolism MH - Fibroblast Growth Factor 2/*metabolism MH - Heparin/*metabolism MH - Hepatocyte Growth Factor/*metabolism MH - Humans MH - Models, Molecular MH - Neuropilin-1/chemistry/*metabolism MH - Polysaccharides/metabolism MH - Protein Isoforms/metabolism MH - Protein Structure, Tertiary MH - Receptor Protein-Tyrosine Kinases/metabolism MH - Receptor, Fibroblast Growth Factor, Type 1 MH - Receptors, Fibroblast Growth Factor/metabolism EDAT- 2005/02/08 09:00 MHDA- 2005/06/23 09:00 CRDT- 2005/02/08 09:00 PHST- 2005/02/08 09:00 [pubmed] PHST- 2005/06/23 09:00 [medline] PHST- 2005/02/08 09:00 [entrez] AID - S0021-9258(19)60414-X [pii] AID - 10.1074/jbc.M410924200 [doi] PST - ppublish SO - J Biol Chem. 2005 Apr 8;280(14):13457-64. doi: 10.1074/jbc.M410924200. Epub 2005 Feb 4.