Reactome | RAC1 and CDC42 activate PAK1

RAC1 and CDC42 activate PAK1

Stable Identifier

R-HSA-2029456

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, plasma membrane

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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