REGULATION OF HUMAN-LEUKOCYTE P21-ACTIVATED KINASES THROUGH G-PROTEIN-COUPLED RECEPTORS

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.