Activation of PAKs by RAC1 and CDC42

Stable Identifier
R-HSA-389788
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol, plasma membrane
ReviewStatus
5/5
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Activation of PAKs by RAC1 and CDC42
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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).
Literature References
PubMed ID Title Journal Year
11804587 Pak1 kinase homodimers are autoinhibited in trans and dissociated upon activation by Cdc42 and Rac1

Parrini, MC, Lei, M, Harrison, SC, Mayer, BJ

Mol Cell 2002
8107774 A brain serine/threonine protein kinase activated by Cdc42 and Rac1

Manser, E, Leung, T, Salihuddin, H, Zhao, ZS, Lim, L

Nature 1994
19513348 Involvement of Rac/Cdc42/PAK pathway in cytoskeletal rearrangements

Szczepanowska, J

Acta Biochim Pol 2009
10470034 p21-activated protein kinase: a crucial component of morphological signaling?

Daniels, RH, Bokoch, GM

Trends Biochem Sci 1999
9535855 Interaction of Rac1 with GTPase-activating proteins and putative effectors. A comparison with Cdc42 and RhoA

Zhang, B, Chernoff, J, Zheng, Y

J. Biol. Chem. 1998
10975528 Structure of PAK1 in an autoinhibited conformation reveals a multistage activation switch

Lei, M, Lu, W, Meng, W, Parrini, MC, Eck, MJ, Mayer, BJ, Harrison, SC

Cell 2000
7559638 Molecular cloning of a new member of the p21-Cdc42/Rac-activated kinase (PAK) family

Manser, E, Chong, C, Zhao, ZS, Leung, T, Michael, G, Hall, C, Lim, L

J. Biol. Chem. 1995
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Authored
Garapati, P V  (2008-07-16)
Reviewed
Bluestone, JA  (2009-06-01)
Esensten, J  (2009-06-01)
Rivero Crespo, F  (2014-12-26)
Created
Garapati, P V  (2009-01-16)
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