title: The interaction of uPAR with VEGFR2 promotes VEGF-induced angiogenesis.
abstract: In endothelial cells, binding of vascular endothelial growth factor (VEGF) to the receptor VEGFR2 activates multiple signaling pathways that trigger processes such as proliferation, survival, and migration that are necessary for angiogenesis. VEGF-bound VEGFR2 becomes internalized, which is a key step in the proangiogenic signal. We showed that the urokinase plasminogen activator receptor (uPAR) interacted with VEGFR2 and described the mechanism by which this interaction mediated VEGF signaling and promoted angiogenesis. Knockdown of uPAR in human umbilical vein endothelial cells (HUVECs) impaired VEGFR2 signaling, and uPAR deficiency in mice prevented VEGF-induced angiogenesis. Upon exposure of HUVECs to VEGF, uPAR recruited the low-density lipoprotein receptor-related protein 1 (LRP-1) to VEGFR2, which induced VEGFR2 internalization. Thus, the uPAR-VEGFR2 interaction is crucial for VEGF signaling in endothelial cells.
authors.affiliation: Molecular Angiogenesis Laboratory, GIGA Research, University of Liège, Avenue de l'Hôpital, 1, 4000 Liège, Belgium. Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy. Department of Biology, University of Padova, Via U. Bassi 58B, 35121 Padova, Italy.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Herkenne
authors.affiliation: Molecular Angiogenesis Laboratory, GIGA Research, University of Liège, Avenue de l'Hôpital, 1, 4000 Liège, Belgium.
authors.forename: Cécile
authors.initials: C
authors.lastname: Paques
authors.affiliation: Molecular Angiogenesis Laboratory, GIGA Research, University of Liège, Avenue de l'Hôpital, 1, 4000 Liège, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: Nivelles
authors.affiliation: Molecular Angiogenesis Laboratory, GIGA Research, University of Liège, Avenue de l'Hôpital, 1, 4000 Liège, Belgium.
authors.forename: Michelle
authors.initials: M
authors.lastname: Lion
authors.affiliation: Molecular Angiogenesis Laboratory, GIGA Research, University of Liège, Avenue de l'Hôpital, 1, 4000 Liège, Belgium. Department of Applied Biology, College of Sciences, University of Sharjah, P.O. Box 27272, Emirates of Sharjah, United Arab Emirates.
authors.forename: Khalid
authors.initials: K
authors.lastname: Bajou
authors.affiliation: Molecular Angiogenesis Laboratory, GIGA Research, University of Liège, Avenue de l'Hôpital, 1, 4000 Liège, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pollenus
authors.affiliation: Molecular Angiogenesis Laboratory, GIGA Research, University of Liège, Avenue de l'Hôpital, 1, 4000 Liège, Belgium.
authors.forename: Marie
authors.initials: M
authors.lastname: Fontaine
authors.affiliation: Laboratory of Angiogenesis and Neurovascular Link, Vesalius Research Center (VRC), Vlaams Instituut Biotechnologie, 3000 Leuven, Belgium. Laboratory of Angiogenesis and Neurovascular Link, VRC, Department of Oncology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.affiliation: Molecular Angiogenesis Laboratory, GIGA Research, University of Liège, Avenue de l'Hôpital, 1, 4000 Liège, Belgium.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Martial
authors.affiliation: Molecular Angiogenesis Laboratory, GIGA Research, University of Liège, Avenue de l'Hôpital, 1, 4000 Liège, Belgium.
authors.forename: Ngoc-Quynh-Nhu
authors.initials: NQ
authors.lastname: Nguyen
authors.affiliation: Molecular Angiogenesis Laboratory, GIGA Research, University of Liège, Avenue de l'Hôpital, 1, 4000 Liège, Belgium. i.struman@ulg.ac.be.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Struman
mesh_terms: D000818:Animals; D004705:Endocytosis; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011485:Protein Binding; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism*; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D019012:Integrin beta1; C475476:LRP1 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D055293:Receptors, Urokinase Plasminogen Activator; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2