Model for PAK1 activation. Inactive PAK1 is localized to the cytoplasm as a homodimer. Upon binding to Nck or Grb2, PAK1 is localized to the plasma membrane and undergoes a slight conformational change that facilitates partial autophosphorylation. PAK1 is now more susceptible to Rac1/Cdc42 binding, leading to a further conformational change, autophosphorylation at T423, and fully active PAK1 kinase activity. PAK1 can also be activated by interaction with Akt, lipids, PIX, FLNa, ETK, JAK2 or by direct T423 phosphorylation by PDK1. (Modified from Parrini et al. 2009)