PI3-kinase (PI3K) catalyzes the phosphorylation of inositol phospholipids at the 3 position to generate phosphatidylinositol 3,4,5-trisphosphate and phosphatidylinositol 3,4-bisphosphate. PIP2 and PIP3 generated serve as lipid substrates where they recruit guanine nucleotide exchange factors (GEFs) like VAV (Proto-oncogene vav) that catalyze the exchange of GDP for GTP on Rac, activating it (Han et al. 1998). VAV2 acts downstream of VEGF to activate Rac1 (Garretta et al. 2007).