VEGF-A/VEGFR2 signaling network in endothelial cells relevant to angiogenesis

J Cell Commun Signal. 2016 Dec;10(4):347-354. doi: 10.1007/s12079-016-0352-8. Epub 2016 Sep 12.


Vascular endothelial growth factor-A (VEGF-A) is essential for endothelial cell functions associated with angiogenesis. Signal transduction networks initiated by VEGFA/VEGFR2, the most prominent ligand-receptor complex in the VEGF system, leads to endothelial cell proliferation, migration, survival and new vessel formation involved in angiogenesis. Considering its biomedical importance, we have developed the first comprehensive map of endothelial cell-specific signaling events of VEGFA/VEGFR2 system pertaining to angiogenesis. Screening over 20,000 published research articles and following the post-translational modification (PTM) and site specificity of VEGFR2, we have documented 240 proteins and their diverse PTM-dependent reactions involved in VEGFA/VEGFR2 signal transduction. From the ligand-receptor complex, this map has been extended to the level of major transcriptionally regulated genes for which the signaling cascades leading to their transcription factors are reported. We believe that this map would serve as a novel platform for reference, integration, and representation and more significantly, the progressive analysis of dynamic features of VEGF signaling in endothelial cells including their cross-talks with other ligand-receptor systems involved in angiogenesis.

Keywords: KDR; Pathway map; Phosphosite mapping; Vascular endothelial growth factor.