CDB25:0003704 HGF — NRP1
Experimentally validated in Human, Mixed species; Orthology-inferred in Human, Mouse, Rat, Frog, Zebrafish, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep
Title
Journal:; Year Published:
Abstract
Interactions of multiple heparin binding growth factors with neuropilin-1 and potentiation of the activity of fibroblast growth factor-2.
The Journal of biological chemistry, 2005; PubMed, Homo sapiens HGF — Rattus norvegicus Nrp1
ABSTRACT: 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.
Neuropilin-1 and neuropilin-2 act as coreceptors, potentiating proangiogenic activity.
Blood, 2008; PubMed, Homo sapiens HGF — Homo sapiens NRP1
ABSTRACT: Neuropilin-1 and -2 (NRP1 and NRP2) are the transmembrane glycoproteins interacting with 2 types of ligands: class III semaphorins and several members of the VEGF family, the main regulators of blood and lymphatic vessel growth. We show here that both NRP1 and NRP2 can also bind hepatocyte growth factor (HGF). HGF is a pleiotropic cytokine and potent proangiogenic molecule that acts on its target cells by binding to the c-met receptor. We found that the N-terminal domain of HGF is involved in the interaction with neuropilins. We demonstrated that invalidation of NRP1 or NRP2 by RNA interference in human umbilical vein endothelial cells (HUVECs) decreased HGF-induced c-met phosphorylation and VEGF-A(165)- and HGF-mediated intracellular signaling. Accordingly, the disruption of NRP1 or NRP2 binding to VEGF-A(165) or HGF with a blocking antibody, decreased the proliferation and migration of endothelial cells. This effect may be further enhanced if VEGF-A(165) or HGF binding to both NRP1 and NRP2 was disrupted. Using a mouse Matrigel model, we demonstrated that NRP1 is essential for HGF-mediated angiogenesis in vivo. Our results suggest that, in endothelial cells, both NRP1 and NRP2 function as proangiogenic coreceptors, potentiating the activity of at least 2 major proangiogenic cytokines, VEGF-A(165) and HGF.