The docking protein FRS2a is a critical regulator of VEGF receptors signaling

Abstract

Vascular endothelial growth factors (VEGFs) signal via their cognate receptor tyrosine kinases designated VEGFR1-3. We report that the docking protein fibroblast growth factor receptor substrate 2 (FRS2a) plays a critical role in cell signaling via these receptors. In vitro FRS2a regulates VEGF-A and VEGF-C-dependent activation of extracellular signal-regulated receptor kinase signaling and blood and lymphatic endothelial cells migration and proliferation. In vivo endothelial-specific deletion of FRS2a results in the profound impairment of postnatal vascular development and adult angiogenesis, lymphangiogenesis, and arteriogenesis.We conclude that FRS2a is a previously unidentified component of VEGF receptors signaling.