RAC1 and CDC42 activate PAK1

Stable Identifier
R-HSA-2029456
Type
Reaction [transition]
Species
Homo sapiens
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PAK1, a downstream effector of CDC42 and RAC1, is found localized in phagosomes. Upon activation, PAK1 phosphorylates LIMK, which directly phosphorylates and inactivates cofilin, a protein that mediates depolymerization of actin filaments. Thus, RAC and CDC42 coordinate actin dynamics by inducing actin polymerization via ARP2/3 on one hand, and inhibiting actin depolyerization via LIMK and cofilin on the other (Garcia-Garcia & Rosales 2002).
PAK1 exists as homodimer in a trans-inhibited conformation. The kinase inhibitory (KI) domain of one PAK1 molecule binds to the C-terminal catalytic domain of the other and inhibits catalytic activity. GTPases RAC1/CDC42 bind the GBD domain of PAK1 thereby altering the conformation of the KI domain, relieving inhibition of its catalytic domain, and allowing PAK1 autophosphorylation that is required for full kinase activity (Parrini et al. 2002, Zhao & Manser 2005).

Literature References
PubMed ID Title Journal Year
12189515 Rapid association of cytoskeletal remodeling proteins with the developing phagosomes of human neutrophils

Robinson, JM, Badwey, JA

Histochem Cell Biol 2002
10496324 Localization of p21-activated kinase 1 (PAK1) to pseudopodia, membrane ruffles, and phagocytic cups in activated human neutrophils

Dharmawardhane, S, Brownson, D, Lennartz, M, Bokoch, GM

J Leukoc Biol 1999
9705280 Structural requirements for PAK activation by Rac GTPases

Knaus, UG, Wang, Y, Reilly, AM, Warnock, D, Jackson, JH

J Biol Chem 1998
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