Recruitment of PAK to the membrane by binding active RAC1

Stable Identifier
R-HSA-2730889
Type
Reaction [binding]
Species
Homo sapiens
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PAK1 kinase is a member of serine/threonine protein kinase family and is widely believed as mediator between Cdc42 and Rac1 and the JNK signal transduction pathway. PAK1 is involved in regulating FCERI mediated mast cell degranulation via effects on calcium mobilisation and cytoskeletal changes (Allen et al. 2009). The conventional PAK family contains a N-terminal conserved Cdc42/Rac-interacting binding domain (CRIB) that overlaps a kinase inhibitory (KI) domain and a C-terminal catalytic domain. PAK1 molecules form trans-inhibited homodimers in which the N-terminal kinase inhibitory (KI) domain of one PAK1 molecule in the dimer binds and inhibits the C-terminal catalytic domain of the other. Isoprenylated Rac1/Cdc42-GTP localized to the membrane recruits PAK1 by binding to the N-terminal CRIB domain. Binding of activated Cdc42/Rac1, breaks the PAK1-dimer and removes the trans-inhibition and stimulates serine/threonine kinase activity of that allows autophosphorylation (Lu & Mayer 1999, Parrini et all. 2009, Zhao et al. 2005).

Literature References
PubMed ID Title Journal Year
19574218 Dissecting activation of the PAK1 kinase at protrusions in living cells

Parrini, MC, Camonis, J, Matsuda, M, de Gunzburg, J

J. Biol. Chem. 2009
9989831 Mechanism of activation of Pak1 kinase by membrane localization

Lu, W, Mayer, BJ

Oncogene 1999
19124833 p21-activated kinase regulates mast cell degranulation via effects on calcium mobilization and cytoskeletal dynamics

Allen, JD, Jaffer, ZM, Park, SJ, Burgin, S, Hofmann, C, Sells, MA, Chen, S, Derr-Yellin, E, Michels, EG, McDaniel, A, Bessler, WK, Ingram, DA, Atkinson, SJ, Travers, JB, Chernoff, J, Clapp, DW

Blood 2009
15548136 PAK and other Rho-associated kinases--effectors with surprisingly diverse mechanisms of regulation

Zhao, ZS, Manser, E

Biochem J 2005
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