Tyrosine-phosphorylated VAVs act as guanine nucleotide exchange factors (GEFs) for RAC1, catalysing the exchange of bound GDP for GTP. RAC1 is a key regulator for actin cytoskeleton and cell migration and is also a critical component of endothelial NADPH oxidase (Wittmann et al. 2003, Tan et al. 2008, Ushio–Fukai 2007, Pricei et al. 2002). Activated RAC1 then stimulates actin polymerization to form lamellipodia through a number of proteins such as WASP-family veroprilin homologous protein (WAV). WAVE proteins stimulate the formation of a branched actin network by binding to the p21 subunit of the ARP2/3 nucleating complex, which is located on the sides of the pre-existing filaments.