Fig. 5

Interactions of vascular endothelial growth factor receptors (VEGFR) with co-receptors and structural features of Neuropilin. a Interaction of VEGFR1 with co-receptors NRP1 and NRP2, α5β1 integrin, and FGFR1. The VEGFR1-NRP2 interaction facilitates VEGF-A121 binding, whereas VEGFR1 engagement with α5β1 promotes EC adhesion to the extracellular matrix. Additionally, the interaction of VEGFR1 with FGFR1 blocks FGF2-induced angiogenesis, highlighting the role of the VEGFR1 complex in modulating angiogenic signaling pathways and EC behavior. b Association of VEGFR2 with various co-receptors and adhesion molecules, including NRPs (NRP1 and NRP2), PDGFRβ, EGFR, CD44, EphA4, VE-Cadherin, and c-Met. These interactions contribute to the specificity and complexity of VEGF signaling, enabling crosstalk between VEGF receptors and other signaling pathways. Such an association with co-receptors and adhesion molecules enhances cellular responses, including EC migration, adhesion, and survival, supporting key physiological processes such as angiogenesis, vascular maturation, and cellular adhesion dynamics within the VEGF pathway. c Interaction between VEGFR3 and the co-receptor NRP2, which plays a critical role in promoting lymphangiogenesis and supporting EC survival. d NRP is shown with additional structural motifs, including the CUB, FV/VIII, MAM, and SEA domains. These domains contribute to receptor interactions and enhance signaling specificity within the VEGF pathway, potentially influencing binding affinities and receptor-ligand selectivity. NRP neuropilin, FGFR fibroblast growth factor receptor, PDGFR platelet-derived growth factor receptor, EGFR epidermal growth factor receptor. Created in BioRendender.com