Robo4 and VEGF signaling pathways crosstalk (WP3943)

This pathway is based on Figure 2 of "Robo4" ( The gene Robo4 plays a role in regulating vascular stability in mice. Robo4 inhibits the gene Notch1, which regulates tip cell formation, in order to create more tip cells. Robo4 also inhibits cell migration, decreasing vessel complexity. The combination of Slit2 and Robo4 inhibits the activation of Src by VEGF-165 and VEGFR2. This inhibition reduces vascular leakage of Evans Blue from retinal blood vessels. More experimentation is necessary to determine whether Robo4 will inhibit other members of the Src family. Proteins on this pathway have targeted assays available via the [ CPTAC Assay Portal]
last edited


Khanspers and Eweitz

Cited In


Homo sapiens



Pathway Ontology: regulatory pathway Notch signaling pathway regulatory pathway Notch signaling pathway


Label Type Compact Identifier
ROBO4 GeneProduct ensembl:ENSG00000154133
SLIT2 GeneProduct ensembl:ENSG00000145147
KDR GeneProduct ensembl:ENSG00000128052
RAC1 GeneProduct ensembl:ENSG00000136238
VEGFA GeneProduct ensembl:ENSG00000112715
SRC GeneProduct ensembl:ENSG00000197122


  1. Weitzman M, Bayley EB, Naik UP. Robo4: a guidance receptor that regulates angiogenesis. Cell Adh Migr. 2008;2(4):220–2. PubMed Europe PMC Scholia