The PAK family of serine/threonine kinases are known to be activated by binding to the GTP-bound form of CDC42 or RAC1, small GTPases of the Rho family that are involved in regulating the organization of the actin cytoskeleton. PAK exists as homodimer in a trans-inhibited conformation. The kinase inhibitory (KI) domain of one PAK molecule binds to the C-terminal catalytic domain of the other and inhibits catalytic activity. Association of GTP-bound forms of CDC42 or RAC1 with the PAK PBD/CRIB domain induces conformational changes in the N-terminal domain that no longer support its autoinhibitory function. CDC42-mediated activation primes PAK2 for superactivation by tyrosine phosphorylation (Renkema et al. 2002).