Prex2 was abundantly expressed in mouse brain and lung, with lower expression in liver, thymus, and spleen. In brain, highest expression was in cerebellum, with lower expression in frontal cortex, striatum, amygdala and hippocampus. In situ hybridization showed that Prex2 mRNA was highly restricted to cerebellum, with expression in Purkinje cells, including dendrites.Expression of PREX2 in PAE cells induced this 'activated Rac' morphology, which was reduced by inhibition of PI3K signaling and enhanced by PDGF stimulation. PREX2-mediated GTP loading onto RAC was synergistically stimulated by PI3K and G protein beta-1 (GNB1)/gamma-2 (GNG2) subunits. Direct binding of phosphatidylinositol 3,4,5-trisphosphate to PREX2 was sufficient to stimulate PREX2 RAC-guanine nucleotide exchange factor activity.