Rac is activated by tyrosine-kinase receptors (RTKs), GPCRs, integrins and stress. Rac activation promotes changes related to cytoskeleton reorganization (left) and other responses (right) through multiple mediators. Rac-GTP induces the activation of WAVE through either Irsp53 or Nap125-PIR121 complexes. WAVE activates Arp2/3, leading to changes in actin cytoskeleton necessary for ruffle formation and cell migration. Rac also activates PAK, which exerts its effects through Arp2/3 and LIMK activation or MLCK inhibition. In addition, Rac forms part of the NADPH oxidase complex that generates reactive oxygen species. Rac/PAK activates MAPKs implicated in stress response, mitogenesis, and survival.