Autophosphorylation of PAK1,2,3

Stable Identifier
R-HSA-5627775
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol, plasma membrane
ReviewStatus
5/5
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Autophosphorylation of PAK1,2,3
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Binding of PAK1, PAK2 or PAK3 to GTP-bound RAC1 or CDC42 disrupts PAK homodimers and allows PAK autophosphorylation. Autophosphorylation of a conserved threonine residue in the catalytic domain of PAKs (T423 in PAK1, T402 in PAK2 and T436 in PAK3) is necessary for the kinase activity of PAK1, PAK2 and PAK3. Autophosphorylation of PAK1 serine residue S144, PAK2 serine residue S141, and PAK3 serine residue S154 disrupts association of PAKs with RAC1 or CDC42 GTPases and enhances kinase activity (Lei et al. 2000, Chong et al. 2001, Parrini et al. 2002, Jung and Traugh 2005, Wang et al. 2011).
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, Mayer, BJ, Harrison, SC

Mol Cell 2002
21098037 Mechanistic studies of the autoactivation of PAK2: a two-step model of cis initiation followed by trans amplification

Wu, JW, Wang, J, Wang, ZX

J. Biol. Chem. 2011
16204230 Regulation of the interaction of Pak2 with Cdc42 via autophosphorylation of serine 141

Traugh, JA, Jung, JH

J Biol Chem 2005
11278486 The mechanism of PAK activation. Autophosphorylation events in both regulatory and kinase domains control activity

Manser, E, Lim, L, Chong, C, Tan, L

J Biol Chem 2001
10975528 Structure of PAK1 in an autoinhibited conformation reveals a multistage activation switch

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

Cell 2000
Participants
Input
Output
Participates
as an event of
Catalyst Activity

protein serine/threonine kinase activity of CDC42:GTP,RAC1:GTP:PAK1,PAK2,PAK3 [plasma membrane]

Physical Entity
CDC42:GTP,RAC1:GTP:PAK1,PAK2,PAK3 [plasma membrane] (Homo sapiens)
Activity
protein serine/threonine kinase activity (GO:0004674)
Orthologous Events
Autophosphorylation of PAK1,2,3 (Bos taurus)
Autophosphorylation of PAK1,2,3 (Caenorhabditis elegans)
Autophosphorylation of PAK1,2,3 (Canis familiaris)
Autophosphorylation of PAK1,2,3 (Danio rerio)
Autophosphorylation of PAK1,2,3 (Dictyostelium discoideum)
Autophosphorylation of PAK1,2,3 (Drosophila melanogaster)
Autophosphorylation of PAK1,2,3 (Gallus gallus)
Autophosphorylation of PAK1,2,3 (Mus musculus)
Autophosphorylation of PAK1,2,3 (Rattus norvegicus)
Autophosphorylation of PAK1,2,3 (Saccharomyces cerevisiae)
Autophosphorylation of PAK1,2,3 (Schizosaccharomyces pombe)
Autophosphorylation of PAK1,2,3 (Sus scrofa)
Autophosphorylation of PAK1,2,3 (Xenopus tropicalis)
Authored
Orlic-Milacic, M  (2014-10-24)
Rivero Crespo, F  (2014-12-26)
Created
Orlic-Milacic, M  (2014-10-20)
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