Inactive p21-associated kinases (PAKs), PAK1, PAK2 and PAK3, form homodimers that are autoinhibited through in trans interaction between the inhibitory N-terminus of one PAK molecule and the catalytic domain of the other PAK molecule. All PAK isoforms are direct effectors of RAC1 and CDC42 GTPases. RAC1 and CDC42 bind to a highly conserved motif in the amino terminus of PAK known as p21-binding domain (PBD) or Cdc42/Rac interactive binding (CRIB) domain. This binding induces a conformational change that disrupts PAK homodimers and relieves autoinhibition of the catalytic carboxyl terminal domain, thereby inducing autophosphorylation at several sites and enabling the phosphorylation of exogenous substrates (Manser et al. 1994, Manser et al. 1995, Zhang et al. 1998, Lei et al. 2000, Parrini et al. 2002; reviewed by Daniels and Bokoch 1999, Szczepanowska 2009).
Parrini, MC, Lei, M, Mayer, BJ, Harrison, SC
Manser, E, Leung, T, Lim, L, Zhao, ZS, Salihuddin, H
Szczepanowska, J
Bokoch, GM, Daniels, RH
Zhang, B, Chernoff, J, Zheng, Y
Meng, W, Mayer, BJ, Eck, MJ, Lu, W, Parrini, MC, Lei, M, Harrison, SC
Lim, L, Michael, G, Chong, C, Manser, E, Leung, T, Zhao, ZS, Hall, C
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