Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenosine Triphosphate / metabolism
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Enzyme Activation
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GTP-Binding Proteins / metabolism*
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Guanosine Triphosphate / metabolism*
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Humans
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N-Formylmethionine Leucyl-Phenylalanine / pharmacology
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NADH, NADPH Oxidoreductases / metabolism
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NADPH Dehydrogenase / metabolism
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NADPH Oxidases
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Neutrophil Activation
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Neutrophils / enzymology*
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Pertussis Toxin
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Phosphoproteins / metabolism
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Phosphorylation
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Protein Serine-Threonine Kinases / metabolism*
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Recombinant Proteins / metabolism
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Tetradecanoylphorbol Acetate / pharmacology
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Virulence Factors, Bordetella / pharmacology
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p21-Activated Kinases
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rac GTP-Binding Proteins
Substances
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Phosphoproteins
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Recombinant Proteins
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Virulence Factors, Bordetella
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N-Formylmethionine Leucyl-Phenylalanine
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Guanosine Triphosphate
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Adenosine Triphosphate
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NADH, NADPH Oxidoreductases
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NADPH Oxidases
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neutrophil cytosolic factor 1
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NADPH Dehydrogenase
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Pertussis Toxin
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PAK1 protein, human
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PAK2 protein, human
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Protein Serine-Threonine Kinases
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p21-Activated Kinases
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GTP-Binding Proteins
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rac GTP-Binding Proteins
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Tetradecanoylphorbol Acetate