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).
Gerhardt, H, Golding, M, Fruttiger, M, Ruhrberg, C, Lundkvist, A, Abramsson, A, Jeltsch, M, Mitchell, C, Alitalo, K, Shima, D, Betsholtz, C
Renkema, GH, Pulkkinen, K, Saksela, K
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