Indication of a protein kinase C-independent pathway for NADPH oxidase activation in human neutrophils.
A potent tyrosine phosphatase inhibitor, pervanadate, induced (i) translocation of the cytosolic NADPH oxidase factors, p47-phox and p67-phox, to the plasma membrane; and (ii) O2- production in human neutrophils. However, the translocation of p47-phox and p67-phox was inhibited by H-7, a protein kinase C (PKC) inhibitor without markedly affecting O2- production in whole neutrophils. Results from the plasma membrane fraction showed that NADPH oxidase activity in neutrophils treated with pervanadate did not vary in the presence or absence of H-7, despite a lower content of p47-phox and p67-phox in H-7-treated neutrophils. These findings suggest that in addition to the well-known PKC-dependent pathway, there may exist another PKC-independent pathway to activate NADPH oxidase in human neutrophils. This pathway involves protein tyrosine phosphorylation but does not seem to necessitate translocation of p47-phox and p67-phox to the plasma membrane.
Kawakami
N
N
Department of Environmental Biochemistry, Kyoto Pharmaceutical University, Japan.
Takemasa
H
H
Yamaguchi
T
T
Hayakawa
T
T
Shimohama
S
S
Fujimoto
S
S
D004789:Enzyme Activation; D006801:Humans; D019255:NADPH Oxidases / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction
D019255:NADPH Oxidases; D011493:Protein Kinase C