Regulation of human leukocyte p21-activated kinases through G protein--coupled receptors.
The Rac guanosine 5'-triphosphate (GTP)-binding proteins regulate oxidant production by phagocytic leukocytes. Two Ste20-related p21-activated kinases (PAKs) were identified as targets of Rac in human neutrophils. Activity of the approximately 65- and approximately 68-kilodalton PAKs was rapidly stimulated by chemoattractants acting through pertussis toxin-sensitive heterotrimeric GTP-binding proteins (G proteins). Native and recombinant PAKs phosphorylated the p47phox reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase component in a Rac-GTP-dependent manner. The action of PAKs during phagocyte activation by G protein-coupled pathways may contribute to regulation of NADPH oxidase activity.
Knaus
U G
UG
Department of Immunology, Scrippts Research Institute, La Jolla, CA 92037, USA.
Morris
S
S
Dong
H J
HJ
Chernoff
J
J
Bokoch
G M
GM
D000255:Adenosine Triphosphate / Q000378:metabolism; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D009252:NADPH Dehydrogenase / Q000378:metabolism; D019255:NADPH Oxidases; D018375:Neutrophil Activation; D009504:Neutrophils / Q000201:enzymology*; D037342:Pertussis Toxin; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D054462:p21-Activated Kinases; D020744:rac GTP-Binding Proteins
D010750:Phosphoproteins; D011994:Recombinant Proteins; D010566:Virulence Factors, Bordetella; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D009252:NADPH Dehydrogenase; D037342:Pertussis Toxin; C515903:PAK1 protein, human; C515907:PAK2 protein, human; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D019204:GTP-Binding Proteins; D020744:rac GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate