Tyrosine-phosphorylated VAVs bind RAC1:GDP as RAC1 guanine nucleotide exchange factors (GEFs), 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, Ushio–Fukai et al. 2002).