RAC1 is activated from inactive GDP-bound state to active GTP-bound form by the GEF activity of DOCK180:ELMO complex. RAC1 signaling facilitates VEGF-stimulated angiogenesis by regulating endothelial cell migration and vascular permeability. RAC1 promotes migration by stimulating actin reorganisation to form membrane ruffles and lamellipodia. RAC1 is also a critical component of endothelial NADPH oxidase promoting reactive oxygen species (ROS) prodcution. Specifically, VEGF acts through RAC1 to stimulate lamellipodia formation at the leading edge of polarized cells for directional migration, or chemotaxis. RAC1 induces vascular permeability in part by disrupting endothelial cell-cell junctions (Soga et al. 2001a, Soga et al. 2001b, Claesson-Welsh & Welsh, 2013).
guanyl-nucleotide exchange factor activity of CRK:DOCK180:ELMO1,ELMO2:VEGFA:p-6Y-VEGFR2:p-SHB:p-7Y-PTK2:SRC-1:HSP90:p-12Y-BCAR1,VEGFA:p-6Y-VEGFR2:p-SHB:p-7Y-PTK2:SRC-1:HSP90:p-Y31,Y118-PXN [plasma membrane]