The Rac guanosine 5'-triphosphate (GTP)-binding proteins regulate oxid
ant production by phagocytic leukocytes. Two Ste20-related p21-activat
ed kinases (PAKs) were identified as targets of Rac in human neutrophi
ls. Activity of the similar to 65- and similar to 68-kilodalton PAKs w
as rapidly stimulated by chemoattractants acting through pertussis tox
in-sensitive heterotrimeric GTP-binding proteins (G proteins). Native
and recombinant PAKs phos phorylated the p47(phox) reduced nicotinamid
e adenine dinucleotide phosphate (NADPH) oxidase component in a Rac-GT
P-dependent manner. The action of PAKs during phagocyte activation by
G protein-coupled pathways may contribute to regulation of NADPH oxida
se activity.